@article {pmid39186815, year = {2024}, author = {Hertzler, JI and Teng, J and Bernard, AR and Stone, MC and Kline, HL and Mahata, G and Kumar, N and Rolls, MM}, title = {Voltage-gated calcium channels act upstream of adenylyl cyclase Ac78C to promote timely initiation of dendrite regeneration.}, journal = {PLoS genetics}, volume = {20}, number = {8}, pages = {e1011388}, doi = {10.1371/journal.pgen.1011388}, pmid = {39186815}, issn = {1553-7404}, support = {R01 GM085115/GM/NIGMS NIH HHS/United States ; R21 NS117396/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Dendrites/metabolism ; *Adenylyl Cyclases/metabolism/genetics ; *Cyclic AMP/metabolism ; *Calcium/metabolism ; *Calcium Channels, L-Type/metabolism/genetics ; Axons/metabolism/physiology ; Drosophila Proteins/metabolism/genetics ; Drosophila melanogaster/genetics ; Calcium Channels, T-Type/metabolism/genetics ; Calcium Signaling/genetics ; Calcium Channels/metabolism/genetics ; Signal Transduction ; Regeneration/genetics/physiology ; Neurons/metabolism ; Nerve Regeneration/physiology/genetics ; Drosophila/genetics ; }, abstract = {Most neurons are not replaced after injury and thus possess robust intrinsic mechanisms for repair after damage. Axon injury triggers a calcium wave, and calcium and cAMP can augment axon regeneration. In comparison to axon regeneration, dendrite regeneration is poorly understood. To test whether calcium and cAMP might also be involved in dendrite injury signaling, we tracked the responses of Drosophila dendritic arborization neurons to laser severing of axons and dendrites. We found that calcium and subsequently cAMP accumulate in the cell body after both dendrite and axon injury. Two voltage-gated calcium channels (VGCCs), L-Type and T-Type, are required for the calcium influx in response to dendrite injury and play a role in rapid initiation of dendrite regeneration. The AC8 family adenylyl cyclase, Ac78C, is required for cAMP production after dendrite injury and timely initiation of regeneration. Injury-induced cAMP production is sensitive to VGCC reduction, placing calcium upstream of cAMP generation. We propose that two VGCCs initiate global calcium influx in response to dendrite injury followed by production of cAMP by Ac78C. This signaling pathway promotes timely initiation of dendrite regrowth several hours after dendrite damage.}, }
@article {pmid39196305, year = {2024}, author = {Liu, M and Liu, Z and Huang, F and Chen, H and Yang, Z and Zhu, Z}, title = {A high-calcium environment induced ectopic calcification of renal interstitial fibroblasts via TFPI-2-DCHS1-ALP/ENPP1 axis to participate in Randall's plaque formation.}, journal = {Urolithiasis}, volume = {52}, number = {1}, pages = {122}, pmid = {39196305}, issn = {2194-7236}, support = {【2023】NO.16.//Basic Research Program of Qiandongnan Prefecture/ ; 202304058290//Scientific Research Fund Project of Hunan Provincial Health Commission/ ; 2022JJ30977//Natural Science Foundation of Hunan Province/ ; }, mesh = {Humans ; *Calcinosis/pathology/metabolism ; *Fibroblasts/metabolism/pathology ; *Glycoproteins/metabolism/genetics ; Calcium/metabolism ; Kidney/pathology/metabolism ; Alkaline Phosphatase/metabolism ; Kidney Calculi/metabolism/pathology/etiology/genetics ; Cells, Cultured ; }, abstract = {Randall's plaques (RP) serve as anchoring sites for calcium oxalate (CaOx) stones, but the underlying mechanism remains unclear. Renal interstitium with a high-calcium environment is identified as pathogenesis of RP formation where the role of human renal interstitial fibroblasts (hRIFs) was highlighted. Our study aims to elucidate the potential mechanism by which a high-calcium environment drives ectopic calcification of hRIFs to participate in RP formation. Alizarin Red staining demonstrated calcium nodules in hRIFs treated with high-calcium medium. Utilizing transcriptome sequencing, tissue factor pathway inhibitor-2 (TFPI-2) was found to be upregulated in high-calcium-induced hRIFs and RP tissues, and TFPI-2 promoted high-calcium-induced calcification of hRIFs. Subsequently, the downstream regulator of TFPI2 was screened by transcriptome sequencing analysis of hRIFs with TFPI-2 knockdown or overexpressed. Dachsous Cadherin Related 1 (DCHS1) knockdown was identified to suppress the calcification of hRIFs enhanced by TFPI-2. Further investigation revealed that TFPI-2/DCHS1 axis promoted high-calcium-induced calcification of hRIFs via disturbing the balance of ENPP1/ALP activities, but without effect on the canonical osteogenic markers, such as osteopontin (OPN), osteogenic factors runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2). In summary, our study mimicked the high-calcium environment observed in CaOx stone patients with hypercalciuria, and discovered that the high-calcium drove ectopic calcification of hRIFs via a novel TFPI-2-DCHS1-ALP/ENPP1 pathway rather than adaption of osteogenic phenotypes to participate in RP formation.}, }
@article {pmid39182194, year = {2024}, author = {Zhu, W and Zhou, Z and Wu, C and Huang, Z and Zhao, R and Wang, X and Luo, L and Liu, Y and Zhong, W and Zhao, Z and Ai, G and Zhong, J and Liu, S and Liu, W and Pang, X and Sun, Y and Zeng, G}, title = {miR-148b-5p regulates hypercalciuria and calcium-containing nephrolithiasis.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {81}, number = {1}, pages = {369}, pmid = {39182194}, issn = {1420-9071}, support = {82070721//National Natural Science Foundation of China/ ; 82270822//National Natural Science Foundation of China/ ; 2024A1515011644//Natural Science Foundation of Guangdong Province/ ; 202102010150//the Young Talent Support Project of Guangzhou Association for Science and Technology, the Guangzhou Science Technology and Innovation Commission/ ; 2023A04J0574//the Young Talent Support Project of Guangzhou Association for Science and Technology, the Guangzhou Science Technology and Innovation Commission/ ; 2020YFC2002700//National Key Research and Development Program/ ; }, mesh = {*MicroRNAs/genetics/metabolism ; Animals ; Humans ; *Hypercalciuria/genetics/metabolism/pathology ; *Calcium/metabolism ; Mice ; Rats ; *Nephrolithiasis/metabolism/genetics/pathology ; Male ; Mice, Inbred C57BL ; Kidney Calculi/metabolism/genetics ; Rats, Sprague-Dawley ; Exosomes/metabolism/genetics ; Female ; Kidney/metabolism/pathology ; Mice, Knockout ; Signal Transduction ; }, abstract = {Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis.}, }
@article {pmid38641658, year = {2024}, author = {Staruschenko, A and Alexander, RT and Caplan, MJ and Ilatovskaya, DV}, title = {Calcium signalling and transport in the kidney.}, journal = {Nature reviews. Nephrology}, volume = {20}, number = {8}, pages = {541-555}, pmid = {38641658}, issn = {1759-507X}, support = {R01 HL148114/HL/NHLBI NIH HHS/United States ; U54 HL169191/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Calcium Signaling/physiology ; *Kidney/metabolism ; *Calcium/metabolism ; *Calcium Channels/metabolism ; Animals ; Homeostasis/physiology ; }, abstract = {The kidney plays a pivotal role in regulating calcium levels within the body. Approximately 98% of the filtered calcium is reabsorbed in the nephron, and this process is tightly controlled to maintain calcium homeostasis, which is required to facilitate optimal bone mineralization, preserve serum calcium levels within a narrow range, and support intracellular signalling mechanisms. The maintenance of these functions is attributed to a delicate balance achieved by various calcium channels, transporters, and calcium-binding proteins in renal cells. Perturbation of this balance due to deficiency or dysfunction of calcium channels and calcium-binding proteins can lead to severe complications. For example, polycystic kidney disease is linked to aberrant calcium transport and signalling. Furthermore, dysregulation of calcium levels can promote the formation of kidney stones. This Review provides an updated description of the key aspects of calcium handling in the kidney, focusing on the function of various calcium channels and the physiological stimuli that control these channels or are communicated through them. A discussion of the role of calcium as an intracellular second messenger and the pathophysiology of renal calcium dysregulation, as well as a summary of gaps in knowledge and future prospects, are also included.}, }
@article {pmid39003275, year = {2024}, author = {Wei, Y and Dang, GP and Ren, ZY and Wan, MC and Wang, CY and Li, HB and Zhang, T and Tay, FR and Niu, LN}, title = {Recent advances in the pathogenesis and prevention strategies of dental calculus.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {56}, pmid = {39003275}, issn = {2055-5008}, support = {82170798//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170798//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170798//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170798//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170798//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170798//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170798//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170798//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82170978//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {*Dental Calculus/microbiology/prevention & control ; Humans ; Animals ; *Biofilms/growth & development ; Bacteria/classification ; Oral Health ; Mouth/microbiology ; Calcium/metabolism ; Phosphorus/metabolism ; }, abstract = {Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.}, }
@article {pmid38896256, year = {2024}, author = {Chen, WC and Chen, YC and Chen, YH and Liu, TY and Tsai, CH and Tsai, FJ}, title = {Identification of novel genetic susceptibility loci for calcium-containing kidney stone disease by genome-wide association study and polygenic risk score in a Taiwanese population.}, journal = {Urolithiasis}, volume = {52}, number = {1}, pages = {94}, pmid = {38896256}, issn = {2194-7236}, support = {DMR-113-053 and CMU112-S-04//China Medical University/ ; }, mesh = {Humans ; *Genome-Wide Association Study ; Female ; Male ; *Genetic Predisposition to Disease ; *Kidney Calculi/genetics/urine ; Middle Aged ; *Polymorphism, Single Nucleotide ; Taiwan/epidemiology ; Adult ; Multifactorial Inheritance ; Calcium/urine/blood/metabolism ; Aged ; Case-Control Studies ; Genetic Loci ; Gene Frequency ; Genetic Risk Score ; }, abstract = {Approximately 80% of kidney stone diseases contain calcium. Inherited genetic factors are among the variables that influence the development of calcium-containing kidney stone diseases (CKSD). Previous genome-wide association studies (GWAS) on stone diseases have been reported worldwide; however, these are not focused on calcium-containing stones. We conducted a GWAS to identify germline genetic polymorphisms associated with CKSD in a Medical Center in Taiwan; hence, this study was based primarily on a hospital-based database. CKSD was diagnosed using the chart records. Patients infected with urea-splitting-microorganisms and those with at least two urinary pH value below 5.5 were excluded. None of the patients had cystic stones based on stone analysis. Those over 40 years of age with no history of CKSD and no microscopic hematuria on urinalysis were considered as controls. The DNA isolated from the blood of 14,934 patients (63.7% male and 36.3% female) with CKSD and 29,868 controls (10,830 men and 19,038 women) at a medical center was genotyped for approximately 714,457 single nucleotide polymorphisms (SNPs) with minor allele frequency of ≥ 0.05. We used PLINK 1.9 to calculate the polygenic risk score (PRS) to investigate the association between CKSD and controls. The accuracy of the PRS was verified by dividing it into the training and testing groups. The statistical analyses were calculated with the area under the curve (AUC) using IBM SPSS version 22. We identified 432 susceptibility loci that reached a genome-wide threshold of P < 1.0 × 10[- 5]. A total of 132 SNPs reached a threshold of P < 5 × 10[- 8] using a stricter definition of significance on chromosomes 4, 13, 16, 17, and 18. At the top locus of our study, SNPs in DGKH, PDILT, BCAS3, and ABCG2 have been previously reported. RN7SKP27, HDAC4, PCDH15, AP003068.2, and NFATC1 were novel findings in this study. PRS was adjusted for sex and age, resulting in an AUC of 0.65. The number of patients in the top quartile of PRS was 1.39 folds in the risk of CKSD than patients in the bottom quartile. Our data identified the significance of GWAS for patients with CKSD in a hospital-based study. The PRS also had a high AUC for discriminating patients with CKSD from controls. A total of 132 SNP loci of SNPs significantly associated with the development of CKSD. This first survey, which focused on patients with CKSD, will provide novel insights specific to CKSD and its potential clinical biomarkers.}, }
@article {pmid38646844, year = {2024}, author = {Wang, Z and Liu, L and Zhao, YW and Tong, XY and Tang, GH and Ouyang, JM}, title = {Carboxymethylated Desmodium styracifolium polysaccharide reduces the risk of calcium oxalate kidney stone formation by inhibiting crystal adhesion and promoting crystal endocytosis.}, journal = {Journal of cellular physiology}, volume = {239}, number = {6}, pages = {e31272}, doi = {10.1002/jcp.31272}, pmid = {38646844}, issn = {1097-4652}, support = {82270800//National Natural Science Foundation of China/ ; 21975105//National Natural Science Foundation of China/ ; 202204054938//Scientific Research Project of Hunan Provincial Health Commission/ ; 2021SK4017//Clinical Research Center For Pediatric Genitourinary Disease In Hunan Province/ ; }, mesh = {Humans ; *Calcium Oxalate/metabolism ; Cell Adhesion/drug effects ; Cell Line ; Crystallization ; *Endocytosis/drug effects ; Epithelial Cells/drug effects/metabolism/pathology ; *Kidney Calculi/prevention &amp; control/drug therapy ; Kidney Tubules, Proximal/drug effects/pathology/metabolism ; Oxidative Stress/drug effects ; *Polysaccharides/pharmacology/chemistry ; Cell Survival/drug effects ; Cell Cycle/drug effects ; Calcium/metabolism ; Intracellular Space/metabolism ; Reactive Oxygen Species/metabolism ; Membrane Potential, Mitochondrial/drug effects ; }, abstract = {The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.}, }
@article {pmid38732005, year = {2024}, author = {Gombedza, FC and Shin, S and Sadiua, J and Stackhouse, GB and Bandyopadhyay, BC}, title = {The Rise in Tubular pH during Hypercalciuria Exacerbates Calcium Stone Formation.}, journal = {International journal of molecular sciences}, volume = {25}, number = {9}, pages = {}, doi = {10.3390/ijms25094787}, pmid = {38732005}, issn = {1422-0067}, support = {DK102043/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Hypercalciuria/metabolism/genetics ; Hydrogen-Ion Concentration ; Mice ; *Mice, Knockout ; *Calcium Oxalate/metabolism ; *Kidney Calculi/metabolism/etiology/pathology ; Calcium Phosphates/metabolism ; Nephrolithiasis/metabolism/genetics/pathology ; Calcium/metabolism ; TRPC Cation Channels/metabolism/genetics ; Kidney Tubules, Proximal/metabolism/pathology ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Acetazolamide/pharmacology ; }, abstract = {In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is found as the core component. The nucleation of CaP could be the first step of CaP+CaOx (mixed) stone formation. High urinary supersaturation of CaP due to hypercalciuria and an elevated urine pH have been described as the two main factors in the nucleation of CaP crystals. Our previous in vivo findings (in mice) show that transient receptor potential canonical type 3 (TRPC3)-mediated Ca[2+] entry triggers a transepithelial Ca[2+] flux to regulate proximal tubular (PT) luminal [Ca[2+]], and TRPC3-knockout (KO; -/-) mice exhibited moderate hypercalciuria and microcrystal formation at the loop of Henle (LOH). Therefore, we utilized TRPC3 KO mice and exposed them to both hypercalciuric [2% calcium gluconate (CaG) treatment] and alkalineuric conditions [0.08% acetazolamide (ACZ) treatment] to generate a CaNL phenotype. Our results revealed a significant CaP and mixed crystal formation in those treated KO mice (KOT) compared to their WT counterparts (WTT). Importantly, prolonged exposure to CaG and ACZ resulted in a further increase in crystal size for both treated groups (WTT and KOT), but the KOT mice crystal sizes were markedly larger. Moreover, kidney tissue sections of the KOT mice displayed a greater CaP and mixed microcrystal formation than the kidney sections of the WTT group, specifically in the outer and inner medullary and calyceal region; thus, a higher degree of calcifications and mixed calcium lithiasis in the kidneys of the KOT group was displayed. In our effort to find the Ca[2+] signaling pathophysiology of PT cells, we found that PT cells from both treated groups (WTT and KOT) elicited a larger Ca[2+] entry compared to the WT counterparts because of significant inhibition by the store-operated Ca[2+] entry (SOCE) inhibitor, Pyr6. In the presence of both SOCE (Pyr6) and ROCE (receptor-operated Ca[2+] entry) inhibitors (Pyr10), Ca[2+] entry by WTT cells was moderately inhibited, suggesting that the Ca[2+] and pH levels exerted sensitivity changes in response to ROCE and SOCE. An assessment of the gene expression profiles in the PT cells of WTT and KOT mice revealed a safeguarding effect of TRPC3 against detrimental processes (calcification, fibrosis, inflammation, and apoptosis) in the presence of higher pH and hypercalciuric conditions in mice. Together, these findings show that compromise in both the ROCE and SOCE mechanisms in the absence of TRPC3 under hypercalciuric plus higher tubular pH conditions results in higher CaP and mixed crystal formation and that TRPC3 is protective against those adverse effects.}, }
@article {pmid38497124, year = {2024}, author = {Caroline, H and Clemence, B and Remi, C and Camille, SJ and Sophie, P and Isabelle, W and Jean-Noel, T and Françoise, M and Emmanuel, L and David, B and Michel, D and Vincent, F and Jean-Philippe, H}, title = {Comparison of normocalcemic versus hypercalcemic primary hyperparathyroidism in a hypercalciuric renal stone population.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgae162}, pmid = {38497124}, issn = {1945-7197}, abstract = {CONTEXT: Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed.<br><br>OBJECTIVE: Our objective was to compare hypercalcemic hyperparathyroidism (HPHPT) versus NHPT hypercalciuric renal stone patients.<br><br>DESIGN AND SETTING: We took advantage of a routine calcium load test performed in hypercalciuric renal stone patients to assess retrospectively among PHPT patients, prevalence and characteristics of NHPT and HPHPT under a calcium restricted diet.<br><br>RESULTS: Among 1671 hypercalciuric patients included, 91 patients have a final diagnosis of PHPT(post load ionized calcium (iCa)>1.31 mmol/L and PTH>30 pg/ml). Prevalence of NHPT is 40% of all PHPT, however according to total serum calcium 4/35 NHPT and 7/56 HPHPT would have been misclassified in the other group. 18/35 NHPT and 40/56 HPHPT underwent parathyroidectomy. No significant characteristics related to parathyroid weight, stone composition or bone remodeling biomarkers is detected between groups. Whereas iCa is higher in HPHPT in fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Of notice, renal calcium excretion (FECa) post load increases by 303% in NHPT but only 176% in HPHPT (p=0.01) likely explained by a lesser PTH decrease (p=0.02). However, a strong negative association (p<0.0001) detected between pooled pre and post load iCa and PTH only in NHPT group suggests a persistent efficient PTH-CaSR control within parathyroid glands in this group.<br><br>CONCLUSION: Our data show the relevance of dynamic tests to unmask NHPT in hypercalciuric renal stone patients.}, }
@article {pmid38397450, year = {2024}, author = {Wang, G and Mi, J and Bai, J and He, Q and Li, X and Wang, Z}, title = {Non-Coding RNAs in Kidney Stones.}, journal = {Biomolecules}, volume = {14}, number = {2}, pages = {}, doi = {10.3390/biom14020213}, pmid = {38397450}, issn = {2218-273X}, support = {CY2021-MS-A12//Cuiying Scientifific and Technological Innovation Program of Lanzhou University Second Hospital/ ; 82160146//the National Natural Science Foundation of China/ ; }, abstract = {Nephrolithiasis is a major public health concern associated with high morbidity and recurrence. Despite decades of research, the pathogenesis of nephrolithiasis remains incompletely understood, and effective prevention is lacking. An increasing body of evidence suggests that non-coding RNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a role in stone formation and stone-related kidney injury. MiRNAs have been studied quite extensively in nephrolithiasis, and a plethora of specific miRNAs have been implicated in the pathogenesis of nephrolithiasis, involving remarkable changes in calcium metabolism, oxalate metabolism, oxidative stress, cell-crystal adhesion, cellular autophagy, apoptosis, and macrophage (Mp) polarization and metabolism. Emerging evidence suggests a potential for miRNAs as novel diagnostic biomarkers of nephrolithiasis. LncRNAs act as competing endogenous RNAs (ceRNAs) to bind miRNAs, thereby modulating mRNA expression to participate in the regulation of physiological mechanisms in kidney stones. Small interfering RNAs (siRNAs) may provide a novel approach to kidney stone prevention and treatment by treating related metabolic conditions that cause kidney stones. Further investigation into these non-coding RNAs will generate novel insights into the mechanisms of renal stone formation and stone-related renal injury and might lead to new strategies for diagnosing and treating this disease.}, }
@article {pmid37964974, year = {2023}, author = {Li, S and Li, H and Wang, Z and Duan, C}, title = {Stanniocalcin 1a regulates organismal calcium balance and survival by suppressing Trpv6 expression and inhibiting IGF signaling in zebrafish.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1276348}, pmid = {37964974}, issn = {1664-2392}, mesh = {Animals ; *Zebrafish/metabolism ; *Calcium/metabolism ; Glycoproteins/genetics/metabolism ; Signal Transduction ; Calcium, Dietary ; }, abstract = {Stanniocalcin 1 (Stc1) is well known for its role in regulating calcium uptake in fish by acting on ionocytes or NaR cells. A hallmark of NaR cells is the expression of Trpv6, a constitutively open calcium channel. Recent studies in zebrafish suggest that genetical deletion of Stc1a and Trpv6 individually both increases IGF signaling and NaR cell proliferation. While trpv6[-/-] fish suffered from calcium deficiency and died prematurely, stc1a[-/-] fish had elevated body calcium levels but also died prematurely. The relationship between Stc1a, Trpv6, and IGF signaling in regulating calcium homeostasis and organismal survival is unclear. Here we report that loss of Stc1a increases Trpv6 expression in NaR cells in an IGF signaling-dependent manner. Treatment with CdCl2, a Trpv6 inhibitor, reduced NaR cell number in stc1a [-/-] fish to the sibling levels. Genetic and biochemical analysis results suggest that Stc1a and Trpv6 regulate NaR cell proliferation via the same IGF pathway. Alizarin red staining detected abnormal calcium deposits in the yolk sac region and kidney stone-like structures in stc1a [-/-] fish. Double knockout or pharmacological inhibition of Trpv6 alleviated these phenotypes, suggesting that Stc1a inhibit epithelial Ca[2+] uptake by regulating Trpv6 expression and activity. stc1a[-/-] mutant fish developed cardiac edema, body swelling, and died prematurely. Treatment of stc1a[-/-] fish with CdCl2 or double knockout of Trpv6 alleviated these phenotypes. These results provide evidence that Stc1a regulates calcium homeostasis and organismal survival by suppressing Trpv6 expression and inhibiting IGF signaling in ionocytes.}, }
@article {pmid38244092, year = {2024}, author = {Cong, X and Huang, L and Wang, X and Li, L and Zhang, X and Chen, X and Xu, Y}, title = {Comparison of the bone mineral density status of patients with kidney stones stratified by stone composition.}, journal = {World journal of urology}, volume = {42}, number = {1}, pages = {42}, pmid = {38244092}, issn = {1433-8726}, mesh = {Humans ; Male ; Female ; *Bone Density ; Calcium Oxalate ; Calcium/metabolism ; *Kidney Calculi/urine ; Lumbar Vertebrae/diagnostic imaging/metabolism ; }, abstract = {PURPOSE: Bone loss has been found to occur frequently in patients with particular metabolic disorders that are likely associated with certain kidney stone composition. Thus, we compared the bone mineral density (BMD) of patients with different kidney stone compositions.<br><br>PATIENTS AND METHODS: A total of 204 consecutive patients who exhibited stone formation with calcium oxalate (CaOx), calcium phosphate (CaP), uric acid (UA), and magnesium ammonium phosphate (MAP) underwent 24&#xa0;h urine test and BMD measurement. BMD was measured by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN). The Z-score was used to express BMD. A BMD Z-score&#x2009;&#x2264;&#x2009;&#x2009;-&#x2009;2 was defined as a diagnostic threshold for bone loss.<br><br>RESULTS: Amongst the patients, 38 had an LS BMD Z-score of&#x2009;&#x2264;&#x2009;&#x2009;-&#x2009;2, but only 2 had FN BMD Z-score of&#x2009;&#x2264;&#x2009;&#x2009;-&#x2009;2. The group with an LS BMD Z-score of&#x2009;&#x2264;&#x2009;&#x2009;-&#x2009;2 exhibited significantly larger male&#x2009;-&#x2009;female ratio, higher frequency of hypercalciuria and CaP, and lower frequency of MAP than the group with an LS BMD Z-score of&#x2009;>&#x2009;&#x2009;-&#x2009;2. Reduced LS BMD was most remarkable in the CaP group, followed by the CaOx, UA, and MAP groups. The LS BMD Z-score of hypercalciuric patients was significantly lower than that of normocalciuric patients only in the CaP group.<br><br>CONCLUSION: Patients with different kidney stone compositions presented different BMD status. Using this information may facilitate medical decision-making in patients with kidney stone who should undergone BMD earlier.}, }
@article {pmid37190798, year = {2024}, author = {Liu, WR and Li, MT and Zhou, Q and Gao, SY and Hou, JB and Yang, GB and Liu, NM and Jia-Yan,  and Yu, JP and Cheng, J and Guo, ZY}, title = {Study on Fu-Fang-Jin-Qian-Cao Inhibiting Autophagy in Calcium Oxalate-induced Renal Injury by UHPLC/Q-TOF-MS-based Metabonomics and Network Pharmacology Approaches.}, journal = {Combinatorial chemistry &amp; high throughput screening}, volume = {27}, number = {1}, pages = {90-100}, doi = {10.2174/1386207326666230515151302}, pmid = {37190798}, issn = {1875-5402}, support = {20191005//Key Specialty Construction Project of Changning District of Shanghai/ ; 82074261, 81903962//Natural Science Foundation of China/ ; PWRq2021-38//Talents Training Program of Pudong Health Commission of Shanghai/ ; QMX2022-01//Talents Training Program of the Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine/ ; }, mesh = {Mice ; Animals ; *Calcium Oxalate/metabolism/pharmacology ; Calcium/metabolism ; Chromatography, High Pressure Liquid ; Network Pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Reactive Oxygen Species/metabolism ; Kidney/metabolism ; Autophagy ; *Drugs, Chinese Herbal/pharmacology/metabolism ; }, abstract = {INTRODUCTION: Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi. Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal injury by inhibiting ROS-mediated autopathy. The mechanism still needs further exploration. Metabonomics is a new subject; the combination of metabolomics and network pharmacology can find pathways for drugs to act on targets more efficiently.<br><br>METHODS: Comprehensive metabolomics and network pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced renal injury. Based on UHPLC-Q-TOF-MS, combined with biochemical analysis, a mice model of Calcium oxalateinduced renal injury was established to study the therapeutic effect of Fu-Fang-Jin-Qian-Cao. Based on the network pharmacology, the target signaling pathway and the protective effect of Fu- Fang-Jin-Qian-Cao on Calcium oxalate-induced renal injury by inhibiting autophagy were explored. Autophagy-related proteins LC3-II, BECN1, ATG5, and ATG7 were studied by immunohistochemistry.<br><br>RESULTS: Combining network pharmacology and metabolomics, 50 differential metabolites and 2482 targets related to these metabolites were found. Subsequently, the targets enriched in PI3KAkt, MAPK and Ras signaling pathways. LC3-II, BECN1, ATG5 and ATG7 were up-regulated in Calcium oxalate-induced renal injury. All of them could be reversed after the Fu-Fang-Jin-Qian- Cao treatment.<br><br>CONCLUSIONS: Fu-Fang-Jin-Qian-Cao can reverse ROS-induced activation of the MAPK signaling pathway and inhibition of the PI3K-Akt signaling pathway, thereby reducing autophagy damage of renal tubular epithelial cells in Calcium oxalate-induced renal injury.}, }
@article {pmid38015778, year = {2023}, author = {Tang, OW and Tang, J}, title = {Idiopathic Hypercalciuria - A Major Metabolic Risk for Calcium Kidney Stone Disease.}, journal = {Rhode Island medical journal (2013)}, volume = {106}, number = {11}, pages = {9-13}, pmid = {38015778}, issn = {2327-2228}, mesh = {Animals ; Humans ; *Hypercalciuria/complications/metabolism ; Calcium/metabolism ; *Kidney Calculi/complications/metabolism ; Kidney/metabolism ; }, abstract = {Idiopathic hypercalciuria is defined as excessive urine calcium excretion in the absence of an identifiable cause. It has been strongly associated with the risk of calcium kidney stone formation. Animal and human studies have suggested excessive bone mineral loss or increased gastrointestinal calcium absorption with abnormal renal calcium excretion may contribute to this process. In this article we will review the complex pathophysiology of idiopathic hypercalciuria and discuss clinical management and challenges.}, }
@article {pmid37823200, year = {2023}, author = {Prochaska, M and Menezes, C and Ko, BS and Coe, F and Worcester, E}, title = {Contribution of thick ascending limb and distal convoluted tubule to glucose-induced hypercalciuria in healthy controls.}, journal = {American journal of physiology. Renal physiology}, volume = {325}, number = {6}, pages = {F811-F816}, doi = {10.1152/ajprenal.00130.2023}, pmid = {37823200}, issn = {1522-1466}, support = {DK127252//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; PO1 DK56788//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; }, mesh = {Humans ; *Calcium/metabolism ; Hypercalciuria/chemically induced ; Glucose ; Magnesium/metabolism ; Receptors, Calcium-Sensing/metabolism ; Parathyroid Hormone/metabolism ; *Kidney Calculi ; Calcium, Dietary/metabolism ; Carrier Proteins ; }, abstract = {Carbohydrates increase kidney stone risk and increase urine calcium and magnesium. We hypothesize that the effects of glucose as an allosteric modulator of calcium-sensing receptors may mediate this effect. Six healthy subjects were on a low-sodium diet before consuming 100 g of glucose beverage. Timed fasting (3) and postglucose (6) urine and blood samples were collected every 30 min. Urine composition and serum markers were measured and microvesicular abundance of tubular transport proteins (NHE3, NKCC2, NCC, and TRPV5) were quantified. Postglucose, serum glucose, and insulin rose rapidly with a parallel increase in calcium and magnesium excretion and no change in fractional excretion of sodium. Both serum parathyroid hormone (PTH) and urine TRPV5 fell in the postglucose periods. The rise in the calcium and magnesium excretion likely occurred primarily in the thick ascending limb where they are both under control of the calcium-sensing receptor. The fall in PTH and TRPV5 support the role of glucose as an allosteric modulator of calcium-sensing receptor.NEW &amp; NOTEWORTHY Sugar increases urine calcium and magnesium as well as kidney stone and bone disease risk. Our study provided new insights into the underlying mechanism as we gave healthy subjects an oral glucose load and used newer tools such as fractional excretion of lithium, serum parathyroid hormone, and microvesicular abundance of tubular transport proteins to characterize the mechanism and identify the thick ascending limb with possible calcium-sensing receptor mediation as a likely contributor to this mechanism.}, }
@article {pmid37568551, year = {2023}, author = {Bauzá, JL and Calvó, P and Julià, F and Guimerà, J and Martínez, AI and Tienza, A and Costa-Bauzá, A and Sanchís, P and Grases, F and Pieras, E}, title = {Relationship between Urinary Parameters and Double-J Stent Encrustation.}, journal = {Journal of clinical medicine}, volume = {12}, number = {15}, pages = {}, doi = {10.3390/jcm12155149}, pmid = {37568551}, issn = {2077-0383}, support = {Leonardo de la Pe&#xf1;a grant//Fundaci&#xf3;n para la Investigaci&#xf3;n en Urolog&#xed;a (FIU) in 2018/ ; PID2019-104331RB-I00//Ministerio de Ciencia e Innovaci&#xf3;n, Agencia Estatal de Investigaci&#xf3;n/ ; }, abstract = {(1) Background: This study aimed to determine the relationship between metabolic urine conditions and the formation, severity, and composition of encrustations in ureteral stents. (2) Methods: Ninety stone-former patients requiring a double-J stent were prospectively enrolled. We collected 24 h metabolic urine samples and demographic data, including indwelling time and previous stone composition. The total deposit weight was obtained, and a macroscopic classification according to the degree of encrustation (null, low, moderate, and high) was created, allowing for intergroup comparisons. Stereoscopic and scanning electron microscopy were performed to identify the type of embedded deposits (calcium oxalate, uric acid, and infectious and non-infectious phosphates). (3) Results: In total, 70% of stents were encrusted; thereof, 42% had a moderate degree of encrustation. The most common encrustation type was calcium oxalate, but infectious phosphates were predominant in the high-encrustation group (p < 0.05). A direct correlation was observed between the purpose-built macroscopic classification and the encrustation weights (p < 0.001). Greater calciuria, uricosuria, indwelling time, and decreased diuresis were observed in stents with a higher degree of encrustation (p < 0.05). The urinary pH values were lower in patients with uric acid encrustations and higher in those with infectious phosphate encrustations (p < 0.05). When compared to non-encrusted stents, patients with calcium-oxalate-encrusted stent showed greater calciuria, phosphaturia, indwelling time, and reduced diuresis; patients with uric-acid-encrusted stent showed greater uricosuria; and patients with infectious and non-infectious phosphate encrustation showed greater urinary pH (p < 0.05). (4) Conclusions: Metabolic urine conditions play a critical role in the formation, composition, and severity of double-J stent encrustation.}, }
@article {pmid37074688, year = {2023}, author = {Alexander, RT}, title = {Kidney stones, hypercalciuria, and recent insights into proximal tubule calcium reabsorption.}, journal = {Current opinion in nephrology and hypertension}, volume = {32}, number = {4}, pages = {359-365}, doi = {10.1097/MNH.0000000000000892}, pmid = {37074688}, issn = {1473-6543}, mesh = {Mice ; Animals ; Humans ; *Calcium/metabolism ; Hypercalciuria/genetics/metabolism ; Claudin-2 ; Genome-Wide Association Study ; *Kidney Calculi/genetics/metabolism ; Calcium, Dietary ; }, abstract = {PURPOSE OF REVIEW: Most kidney stones are composed of calcium, and the greatest risk factor for kidney stone formation is hypercalciuria. Patients who form kidney stones often have reduced calcium reabsorption from the proximal tubule, and increasing this reabsorption is a goal of some dietary and pharmacological treatment strategies to prevent kidney stone recurrence. However, until recently, little was known about the molecular mechanism that mediates calcium reabsorption from the proximal tubule. This review summarizes newly uncovered key insights and discusses how they may inform the treatment of kidney stone formers.<br><br>RECENT FINDINGS: Studies examining claudin-2 and claudin-12 single and double knockout mice, combined with cell culture models, support complementary independent roles for these tight junction proteins in contributing paracellular calcium permeability to the proximal tubule. Moreover, a family with a coding variation in claudin-2 causing hypercalciuria and kidney stones have been reported, and reanalysis of Genome Wide Association Study (GWAS) data demonstrates an association between noncoding variations in CLDN2 and kidney stone formation.<br><br>SUMMARY: The current work begins to delineate the molecular mechanisms whereby calcium is reabsorbed from the proximal tubule and suggests a role for altered claudin-2 mediated calcium reabsorption in the pathogenesis of hypercalciuria and kidney stone formation.}, }
@article {pmid37314254, year = {2023}, author = {Djafarrian, R and Laurent, M and Demarchi, M and Bianchetto Wolf, N and Luzuy-Guarnero, V and Zingg, T and Matter, M and Triponez, F}, title = {[Surgical management of primary hyperparathyroidism].}, journal = {Revue medicale suisse}, volume = {19}, number = {831}, pages = {1162-1168}, doi = {10.53738/REVMED.2023.19.831.1162}, pmid = {37314254}, issn = {1660-9379}, abstract = {Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia due to inappropriate parathyroid hormone (PTH) secretion mostly caused by a single adenoma. Clinical manifestations vary and include bone loss (osteopenia, osteoporosis), kidney stones, asthenia and psychiatric disorders. In 80 % of cases PHPT is asymptomatic. Secondary causes of elevated PTH such as renal insufficiency and/or vitamin D deficiency should be excluded, and 24-hour calciuria should be measured to rule out familial hyocalciuric hypercalcemia. Surgery requires radiological tests: a cervical ultrasound to exclude concomitant thyroid pathology and a functional examination (Sestamibi scintigraphy or F-choline PET scan). Management should be discussed in a multidisciplinary team. Treatment is surgical and can also be offered to asymptomatic patients.}, }
@article {pmid36959633, year = {2023}, author = {Osman, O and Manzi, S and Wasko, MC and Clark, BA}, title = {Case report: disease mechanisms and medical management of calcium nephrolithiasis in rheumatologic diseases.}, journal = {BMC urology}, volume = {23}, number = {1}, pages = {42}, pmid = {36959633}, issn = {1471-2490}, abstract = {BACKGROUND: Nephrolithiasis as a feature of rheumatologic diseases is under recognized. Understanding presenting features, diagnostic testing is crucial to proper management.<br><br>CASE PRESENTATION: A 32&#xa0;year old woman with a history of recurrent complicated nephrolithiasis presented to a rheumatologist for a several month history of fatigue, dry eyes, dry mouth, arthralgias. She had a positive double-stranded DNA, positive SSA and SSB antibodies. She was diagnosed with Systemic Lupus erythematosus (SLE) and Sjogren's syndrome and was started on mycophenalate mofetil. Of relevance was a visit to her local emergency room 4&#xa0;years earlier with profound weakness with unexplained marked hypokalemia and a non-anion gap metabolic acidosis. Approximately one year after that episode she developed flank pain and nephrocalcinosis. She had multiple issues over the ensuing years with stones and infections on both sides. Interventions included extracorporeal shockwave lithotripsy as well as open lithotomy and eventual auto-transplantation of left kidney for recurrent ureteric stenosis. 24&#xa0;h stone profile revealed marked hypocitraturia, normal urine calcium, normal urine oxalate and uric acid. She was treated with potassium citrate. Mycophenolate was eventually stopped due to recurrent urinary tract infections and she was started on Belimumab. Because of recurrent SLE flares, treatment was changed to Rituximab (every 6&#xa0;months) with clinical and serologic improvement. Her kidney stone frequency gradually improved and no further interventions needed although she continued to require citrate repletion for hypocitraturia.<br><br>CONCLUSIONS: Nephrolithiasis can be a prominent and even presenting feature in Sjogrens syndrome as well as other rheumatologic diseases. Prompt recognition and understanding disease mechanisms is important for best therapeutic interventions for kidney stone prevention as well as treatment of underlying bone mineral disease.}, }
@article {pmid36949424, year = {2023}, author = {Musiał, N and Bogucka, A and Tretiakow, D and Skorek, A and Ryl, J and Czaplewska, P}, title = {Proteomic analysis of sialoliths from calcified, lipid and mixed groups as a source of potential biomarkers of deposit formation in the salivary glands.}, journal = {Clinical proteomics}, volume = {20}, number = {1}, pages = {11}, pmid = {36949424}, issn = {1542-6416}, abstract = {Salivary stones, also known as sialoliths, are formed in a pathological situation in the salivary glands. So far, neither the mechanism of their formation nor the factors predisposing to their formation are known despite several hypotheses. While they do not directly threaten human life, they significantly deteriorate the patient's quality of life. Although this is not a typical research material, attempts are made to apply various analytical tools to characterise sialoliths and search for the biomarkers in their proteomes. In this work, we used mass spectrometry and SWATH-MS qualitative and quantitative analysis to investigate the composition and select proteins that may contribute to solid deposits in the salivary glands. Twenty sialoliths, previously characterized spectroscopically and divided into the following groups: calcified (CAL), lipid (LIP) and mixed (MIX), were used for the study. Proteins unique for each of the groups were found, including: for the CAL group among them, e.g. proteins from the S100 group (S100 A8/A12 and P), mucin 7 (MUC7), keratins (KRT1/2/4/5/13), elastase (ELANE) or stomatin (STOM); proteins for the LIP group-transthyretin (TTR), lactotransferrin (LTF), matrix Gla protein (MPG), submandibular gland androgen-regulated protein 3 (SMR3A); mixed stones had the fewest unique proteins. Bacterial proteins present in sialoliths have also been identified. The analysis of the results indicates the possible role of bacterial infections, disturbances in calcium metabolism and neutrophil extracellular traps (NETs) in the formation of sialoliths.}, }
@article {pmid36871182, year = {2023}, author = {Li, Y and Lu, X and Yu, Z and Wang, H and Gao, B}, title = {Meta-data analysis of kidney stone disease highlights ATP1A1 involvement in renal crystal formation.}, journal = {Redox biology}, volume = {61}, number = {}, pages = {102648}, doi = {10.1016/j.redox.2023.102648}, pmid = {36871182}, issn = {2213-2317}, mesh = {Humans ; *Calcium/metabolism ; Kidney/metabolism ; *Kidney Calculi/chemistry/metabolism ; Oxidative Stress/genetics ; Down-Regulation ; Sodium-Potassium-Exchanging ATPase/genetics ; }, abstract = {Nephrolithiasis is a complicated disease affected by various environmental and genetic factors. Crystal-cell adhesion is a critical initiation process during kidney stone formation. However, genes regulated by environmental and genetic factors in this process remain unclear. In the present study, we integrated the gene expression profile data and the whole-exome sequencing data of patients with calcium stones, and found that ATP1A1 might be a key susceptibility gene involved in calcium stone formation. The study showed that the T-allele of rs11540947 in the 5'-untranslated region of ATP1A1 was associated with a higher risk of nephrolithiasis and lower activity of a promoter of ATP1A1. Calcium oxalate crystal deposition decreased ATP1A1 expression in vitro and in vivo and was accompanied by the activation of the ATP1A1/Src/ROS/p38/JNK/NF-κB signaling pathway. However, the overexpression of ATP1A1 or treatment with pNaKtide, a specific inhibitor of the ATP1A1/Src complex, inhibited the ATP1A1/Src signal system and alleviated oxidative stress, inflammatory responses, apoptosis, crystal-cell adhesion, and stone formation. Moreover, the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reversed ATP1A1 down-regulation induced by crystal deposition. In conclusion, this is the first study to show that ATP1A1, a gene modulated by environmental factors and genetic variations, plays an important role in renal crystal formation, suggesting that ATP1A1 may be a potential therapeutic target for treating calcium stones.}, }
@article {pmid36853379, year = {2023}, author = {Zittermann, A and Trummer, C and Theiler-Schwetz, V and Pilz, S}, title = {Long-term supplementation with 3200 to 4000 IU of vitamin D daily and adverse events: a systematic review and meta-analysis of randomized controlled trials.}, journal = {European journal of nutrition}, volume = {}, number = {}, pages = {}, pmid = {36853379}, issn = {1436-6215}, abstract = {PURPOSE: The upper tolerable intake level for vitamin D in the general population has been set at 4000 international units (IU) daily, but considerable uncertainty remains. We summarized reported harmful effects of a daily vitamin D supplement of 3200-4000 IU in trials lasting ≥ 6 months.<br><br>METHODS: We performed a systematic review and meta-analysis of randomized controlled trials in several databases and identified 22 trials reporting safety data. Parameters of calcium metabolism, falls, hospitalization, and mortality were assessed.<br><br>RESULTS: The selected trials comprised a total number of 12,952 participants. All trials used supplemental vitamin D3. The relative risk (RR) of hypercalcemia in the vitamin D vs. control arm was 2.21 (95%CI: 1.26-3.87; 10 studies), with a vitamin D-induced frequency of hypercalcemia of 4 cases per 1000 individuals. Subgroup analysis in trials with&#x2009;>&#x2009;100 and&#x2009;&#x2264;&#x2009;100 study participants revealed an RR of 2.63 (95%CI: 1.30-5.30; 7 studies) and 0.80 (95%CI: 0.24-2.62; 3 studies), respectively (Pinteraction&#x2009;=&#x2009;0.06). Risks of falls and hospitalization were also significantly increased in the vitamin D arm with an RR of 1.25 (95%CI: 1.01-1.55; 4 studies) and 1.16 (95%CI: 1.01-1.33; 7 studies), respectively. Risks of hypercalciuria, kidney stones, and mortality did not differ significantly between study arms. Quality assessment revealed high risk of incomplete reporting of safety-related outcome data.<br><br>CONCLUSION: Supplemental vitamin D doses of 3200-4000&#xa0;IU/d appear to increase the risk of hypercalcemia and some other adverse events in a small proportion of individuals, indicating that this dose is not completely safe. In future studies, rigorous reporting of safety-related outcomes is needed when using moderately high doses of vitamin D.}, }
@article {pmid36790470, year = {2023}, author = {Abdalbary, M and Chishti, E and Shakhashiro, M and Mohamed, R and Parikh, T and Nassar, MK and Sayed-Ahmed, N and Faugere, MC and Sawaya, BP and El-Husseini, A}, title = {Impact of urinary calcium excretion on kidney, bone, and cardiovascular systems in patients with bone biopsy proven osteoporosis: a longitudinal long-term follow-up study.}, journal = {Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA}, volume = {}, number = {}, pages = {}, pmid = {36790470}, issn = {1433-2965}, abstract = {UNLABELLED: The impact of urine calcium on kidney, bone, and cardiovascular systems in osteoporosis is not well-known. In this 7-year-follow-up study, high urine calcium did not affect kidney function but increased risk of kidney stones, while low urine calcium increased cardiovascular diseases. Maintaining normal urine calcium is beneficial for bone health.<br><br>PURPOSE: Hypercalciuria is common in patients with osteoporosis. However, the long-term effect of urinary calcium excretion (UCaE) on patients' health is not well-examined. The current study aims to assess the impact of UCaE on kidney, bone, and cardiovascular outcomes in patients with bone biopsy proven osteoporosis.<br><br>METHODS: Longitudinal study of all patients with osteoporosis who underwent bone biopsy and 24-h urine collection between 2008 and 2015 in the University of Kentucky. DXA scans, serum markers, kidney function, and cardiovascular events were recorded until last clinic visit in 2021. Exclusion criteria were secondary osteoporosis or conditions that might substantially impact UCaE. The significant results in univariate analysis were confirmed in multi-variable regression models involving clinically important covariates that might impact patients' outcomes.<br><br>RESULTS: Study included 230 patients with mean follow-up of 7.2 &#xb1; 2.9 years. The mean age was 61 years, and the mean eGFR at baseline was 85 &#xb1; 19 ml/min/1.73 m[2]. Low bone turnover (LBT) was present in 57% and high bone turnover (HBT) in 43% of patients. Hypercalciuria was found in one-third of patients with no difference between LTB and HTB. UCaE correlated positively with eGFR but did not affect the rate of eGFR decline over time. Higher UCaE predicted kidney stones development. We observed U-shaped effect of UCaE on bone health. Hypercalciuria predicted loss of BMD at all sites, but also hypocalciuria was associated with higher loss in total hip BMD. Upper limb fractures were the most observed fractures, and their incidence was higher in patients with hyper- or hypo-calciuria. Lower UCaE independently predicted development of major adverse cardiac events (MACE) and cardiovascular disease (CVD).<br><br>CONCLUSION: UCaE correlated with eGFR but it did not affect the change of eGFR over time. Patients with normal UCaE had lower incidence of upper limb fractures and less reduction in BMD. Low UCaE predicted MACE and CVD.}, }
@article {pmid36465204, year = {2022}, author = {Zhang, SY and Collingwood, JD and Fujihashi, A and He, K and Oliver, LA and Dangle, P}, title = {Incidence of Emergency Department Presentations of Symptomatic Stone Disease in Pediatric Patients: A Southeastern Study.}, journal = {Cureus}, volume = {14}, number = {11}, pages = {e30979}, pmid = {36465204}, issn = {2168-8184}, abstract = {Background The incidence of nephrolithiasis during childhood has increased significantly over recent decades. Some studies indicate a rapid rise in adolescents, particularly in African American women. This study serves to identify trends in symptomatic pediatric nephrolithiasis presentations to the emergency department (ED) as a result of increasing incidence and to determine associations between demographic variables at our single-site tertiary pediatric hospital in the Southeast United States. Methods After IRB approval, a review of the data provided by the Pediatric Health Information System, a pediatric database that includes clinical and resource utilization data for 51 of the largest children's hospitals in the nation, yielded 644 pediatric occurrences of nephrolithiasis at single-site emergency departments from 2006 to 2020. The percent change and average percent change in three-year intervals were calculated to establish a trend over time. A chi-square test of independence was performed to assess associations between race, gender, and age groups. Results A total of 780 stone occurrences and associated patient demographic data were reviewed for 644 children (364, 56.52% female) with median age of 183 ± 45.11 months (9-397 months). Of the 644 children, 79 (12.3%) were noted to have recurrent symptomatic nephrolithiasis, contributing to 136/780 stone events. There was a marked increase of 84.4% in confirmed pediatric nephrolithiasis occurrences over 15 years, with an average percent increase of 16.1% every three years. A Chi[2] test of independence was performed between gender and age group (>/< 10yr), gender and race, and race and age group. No expected cell frequencies were less than five. There is no statistically significant relationship between gender and age group, χ[2] (1, N=644) = 3.30, p=0.692. There is no significant association between race (Caucasian vs. non-Caucasian) and age group (>/< 10yr), χ[2] (1, N=644) = 0.393, p=0.531. There is a statistically significant relationship between gender and race (Caucasian vs. non-Caucasian), χ[2] (1, N=644) = 5.28, p=0.021. Caucasian females were more likely to present to our tertiary pediatric hospital's emergency department with nephrolithiasis than Caucasian males or non-Caucasian males or females. Additionally, our data reflected a greater percentage of symptomatic nephrolithiasis presentations occurred in the second decade of life (85.4% vs 14.3%, 552 vs 92 stone events). Conclusion Based on our data, there is a marked increase of 84.4% in pediatric nephrolithiasis occurrences from 2006 to 2020, with a mean increase of 16.1% every three years at our single-site tertiary referral pediatric hospital in the Southeast. Among demographic groups, white adolescent females have an increased risk of developing kidney stones.}, }
@article {pmid36409043, year = {2022}, author = {Dent, EL and Ryan, MJ}, title = {Fifty years of impact on treating bone disease: a commentary on Gasser et al.}, journal = {Clinical science (London, England : 1979)}, volume = {136}, number = {22}, pages = {1657-1659}, doi = {10.1042/CS20220040}, pmid = {36409043}, issn = {1470-8736}, mesh = {Humans ; Calcium ; *Bone Density Conservation Agents/therapeutic use ; *Osteoporosis/drug therapy ; Diphosphonates/therapeutic use ; *Kidney Calculi ; }, abstract = {The precise control of whole-body calcium is essential for the maintenance of normal physiological function. Disruptions in calcium homeostasis can lead to pathology including osteoporosis, kidney stone formation, and cardiac arrythmias. During the 1960s and early 1970s, a full understanding of calcium metabolism was still emerging. This commentary spotlights a seminal Clinical Science paper published in 1972 that significantly advanced the field and contributed to the eventual approval of bisphosphonate drugs commonly used to treat postmenopausal osteoporosis, cancer metastases, and other calcium disorders.}, }
@article {pmid36376291, year = {2022}, author = {Fan, G and Baker, MR and Terry, LE and Arige, V and Chen, M and Seryshev, AB and Baker, ML and Ludtke, SJ and Yule, DI and Serysheva, II}, title = {Conformational motions and ligand-binding underlying gating and regulation in IP3R channel.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6942}, pmid = {36376291}, issn = {2041-1723}, support = {R01 GM072804/GM/NIGMS NIH HHS/United States ; R01 GM080139/GM/NIGMS NIH HHS/United States ; }, mesh = {Inositol 1,4,5-Trisphosphate Receptors/metabolism ; *Calcium/metabolism ; Ligands ; Protein Domains ; *Inositol 1,4,5-Trisphosphate/metabolism ; Calcium Signaling ; }, abstract = {Inositol-1,4,5-trisphosphate receptors (IP3Rs) are activated by IP3 and Ca[2+] and their gating is regulated by various intracellular messengers that finely tune the channel activity. Here, using single particle cryo-EM analysis we determined 3D structures of the nanodisc-reconstituted IP3R1 channel in two ligand-bound states. These structures provide unprecedented details governing binding of IP3, Ca[2+] and ATP, revealing conformational changes that couple ligand-binding to channel opening. Using a deep-learning approach and 3D variability analysis we extracted molecular motions of the key protein domains from cryo-EM density data. We find that IP3 binding relies upon intrinsic flexibility of the ARM2 domain in the tetrameric channel. Our results highlight a key role of dynamic side chains in regulating gating behavior of IP3R channels. This work represents a stepping-stone to developing mechanistic understanding of conformational pathways underlying ligand-binding, activation and regulation of the channel.}, }
@article {pmid36227903, year = {2022}, author = {Cabuzu, D and Ramakrishnan, SK and Moor, MB and Harmacek, D and Auberson, M and Durussel, F and Bonny, O}, title = {Loss of Ecrg4 improves calcium oxalate nephropathy.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0275972}, pmid = {36227903}, issn = {1932-6203}, mesh = {Animals ; Calcium/urine ; Calcium Oxalate/chemistry ; Calcium, Dietary ; *Esophageal Neoplasms ; Hypercalciuria ; *Kidney Calculi/epidemiology ; Mice ; RNA, Messenger/genetics ; *Renal Insufficiency ; }, abstract = {Kidney stone is one of the most frequent urinary tract diseases, affecting 10% of the population and displaying a high recurrence rate. Kidney stones are the result of salt supersaturation, including calcium and oxalate. We have previously identified Esophageal cancer-related gene 4 (Ecrg4) as being modulated by hypercalciuria. Ecrg4 was initially described as a tumor suppressor gene in the esophagus. Lately, it was shown to be involved as well in apoptosis, cell senescence, cell migration, inflammation and cell responsiveness to chemotherapy. To the best of our knowledge, nothing is known about ECRG4's function in the renal tissue and its relationship with calciuria. We hypothesized that the increased expression of Ecrg4 mRNA is triggered by hypercalciuria and might modulate intratubular calcium-oxalate precipitation. In this study, we have first (i) validated the increased Ecrg4 mRNA in several types of hypercalciuric mouse models, then (ii) described the Ecrg4 mRNA expression along the nephron and (iii) assessed ECRG4's putative role in calcium oxalate nephropathy. For this, Ecrg4 KO mice were challenged with a kidney stone-inducing diet, rich in calcium and oxalate precursor. Taken together, our study demonstrates that Ecrg4's expression is restricted mainly to the distal part of the nephron and that the Ecrg4 KO mice develop less signs of tubular obstruction and less calcium-oxalate deposits. This promotes Ecrg4 as a modulator of renal crystallization and may open the way to new therapeutic possibilities against calcium oxalate nephropathy.}, }
@article {pmid36227501, year = {2023}, author = {Yuan, S and Ibrahim, IAA and Ren, R}, title = {Anti-urolithiatic Activity of Daidzin in Ethylene Glycol-Induced Urolithiasis in Rats.}, journal = {Applied biochemistry and biotechnology}, volume = {195}, number = {2}, pages = {905-918}, pmid = {36227501}, issn = {1559-0291}, mesh = {Male ; Female ; Humans ; *Kidney/metabolism ; Calcium/metabolism ; Uric Acid/metabolism/pharmacology ; Ethylene Glycol/adverse effects/metabolism ; Creatinine ; Magnesium/metabolism ; *Urolithiasis/chemically induced/drug therapy/metabolism ; Plant Extracts/pharmacology ; Antioxidants/metabolism ; Oxalates/adverse effects/metabolism ; Urea ; }, abstract = {Urolithiasis is a common urological disorder, which causes considerable morbidity in both genders at all age groups worldwide. Though treatment options such as diuretics and non-invasive techniques to disintegrate the deposits are available, but often they are found less effective in the clinics. In this work, we planned to investigate the ameliorative effects of daidzin against the ethylene glycol (EG)-induced urolithiasis in rats. The male albino rats were distributed into four groups (n = 6) as control (group I), urolithiasis induced by the administration of 0.75% EG (group II), urolithiasis induced rats treated with 50 mg/kg of daidzin (group III), and urolithiasis rats treated with standard drug 750 mg/kg of cystone (group IV). The urine volume, pH, and total protein in the urine were assessed. The activities of marker enzymes in both plasma and kidney tissues were analyzed using assay kits. The levels of kidney function markers such as calcium, oxalate, urea, creatinine, uric acid, magnesium, BUN, and phosphorous were estimated using assay kits. The status of antioxidants and inflammatory cytokines were also examined using kits. The renal tissues were examined by histopathological analysis. Our results revealed that the daidzin treatment effectively decreased the urine pH and protein level and increased the urine volume in the urolithiasis rats. Daidzin decreased the calcium, oxalate, uric acid, and urea, creatinine, and BUN levels and also improved the magnesium and phosphorus in the urolithiasis rats. The activities of AST, ALT, ALP, GGT, and LDH were effectively reduced by the daidzin in both serum and renal tissue. Daidzin also reduced the inflammatory marker and increased the antioxidant levels. Histopathology results also proved the therapeutic effects of daidzin. Together, our results displayed that daidzin is effective in the amelioration of EG-induced urolithiasis in rats.}, }
@article {pmid36222344, year = {2022}, author = {Xiao, H and Qin, G and Fang, B}, title = {Nanoparticle-mediated delivery system alleviates the formation of infection stones by activating TRPV5.}, journal = {General physiology and biophysics}, volume = {41}, number = {5}, pages = {465-471}, doi = {10.4149/gpb_2022028}, pmid = {36222344}, issn = {0231-5882}, mesh = {Animals ; Calcium/metabolism ; *Chitosan ; Liposomes ; *Nanoparticles ; RNA ; Rats ; }, abstract = {Infection stones constitute a small but intractable group of diseases of urinary system. In this study, we explored the potential therapeutic effect of a small activation RNA, ds-320, encapsulated in chitosan (320-chitosan). Western blot analysis verified the downregulation of TRPV5 in patients and rat model of infection stones, as well as the stimulation of ds-320 on TRPV5 expression. MTT assay showed that chitosan-mediated delivery was less cytotoxic to ds-320 compared with liposome delivery. Further a modified invasion assay revealed an inhibitory effect of 320-chitosan on bacterial invasion into normal rat kidney epithelial NRK-52E cells. The establishment of infection stone model was performed by intravesical injection of 1×108 CFU of Proteus mirabilis. In animal experiments, no visible stones were obtained. The number of live bacteria and white blood cells in urine showed no difference among all infected rats at the time of sacrifice. However, we observed a decline in urine calcium and pH, suggesting the effect of acidification. Overall, our study provides evidence for the protective effect of 320-chitosan, for its ability to down-regulate urinary calcium, acidify urine, and inhibit bacteria from invading renal epithelial cells. Thus, it can be served as an important complementary therapy for infection stones.}, }
@article {pmid36142492, year = {2022}, author = {Mikhalchik, E and Basyreva, LY and Gusev, SA and Panasenko, OM and Klinov, DV and Barinov, NA and Morozova, OV and Moscalets, AP and Maltseva, LN and Filatova, LY and Pronkin, EA and Bespyatykh, JA and Balabushevich, NG}, title = {Activation of Neutrophils by Mucin-Vaterite Microparticles.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142492}, issn = {1422-0067}, mesh = {Calcium/metabolism ; Calcium Carbonate/pharmacology ; Calcium Oxalate/metabolism ; Interleukin-10/metabolism ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Ions/metabolism ; *Luminol/chemistry ; Magnesium/metabolism ; Mucins/metabolism ; *Neutrophils/metabolism ; Oxidants/pharmacology ; Phosphates/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Zymosan/pharmacology ; }, abstract = {Nano- and microparticles enter the body through the respiratory airways and the digestive system, or form as biominerals in the gall bladder, salivary glands, urinary bladder, kidney, or diabetic pancreas. Calcium, magnesium, and phosphate ions can precipitate from biological fluids in the presence of mucin as hybrid nanoparticles. Calcium carbonate nanocrystallites also trap mucin and are assembled into hybrid microparticles. Both mucin and calcium carbonate polymorphs (calcite, aragonite, and vaterite) are known to be components of such biominerals as gallstones which provoke inflammatory reactions. Our study was aimed at evaluation of neutrophil activation by hybrid vaterite-mucin microparticles (CCM). Vaterite microparticles (CC) and CCM were prepared under standard conditions. The diameter of CC and CCM was 3.3 ± 0.8 µm and 5.8 ± 0.7 µm, with ƺ-potentials of -1 ± 1 mV and -7 ± 1 mV, respectively. CC microparticles injured less than 2% of erythrocytes in 2 h at 1.5 mg mL[-1], and no hemolysis was detected with CCM; this let us exclude direct damage of cellular membranes by microparticles. Activation of neutrophils was analyzed by luminol- and lucigenin-dependent chemiluminescence (Lum-CL and Luc-CL), by cytokine gene expression (IL-6, IL-8, IL-10) and release (IL-1β, IL-6, IL-8, IL-10, TNF-α), and by light microscopy of stained smears. There was a 10-fold and higher increase in the amplitude of Lum-CL and Luc-CL after stimulation of neutrophils with CCM relative to CC. Adsorption of mucin onto prefabricated CC microparticles also contributed to activation of neutrophil CL, unlike mucin adsorption onto yeast cell walls (zymosan); adsorbed mucin partially suppressed zymosan-stimulated production of oxidants by neutrophils. Preliminary treatment of CCM with 0.1-10 mM NaOCl decreased subsequent activation of Lum-CL and Luc-CL of neutrophils depending on the used NaOCl concentration, presumably because of the surface mucin oxidation. Based on the results of ELISA, incubation of neutrophils with CCM downregulated IL-6 production but upregulated that of IL-8. IL-6 and IL-8 gene expression in neutrophils was not affected by CC or CCM according to RT[2]-PCR data, which means that post-translational regulation was involved. Light microscopy revealed adhesion of CC and CCM microparticles onto the neutrophils; CCM increased neutrophil aggregation with a tendency to form neutrophil extracellular traps (NETs). We came to the conclusion that the main features of neutrophil reaction to mucin-vaterite hybrid microparticles are increased oxidant production, cell aggregation, and NET-like structure formation, but without significant cytokine release (except for IL-8). This effect of mucin is not anion-specific since particles of powdered kidney stone (mainly calcium oxalate) in the present study or calcium phosphate nanowires in our previous report also activated Lum-CL and Luc-CL response of neutrophils after mucin sorption.}, }
@article {pmid36139105, year = {2022}, author = {Tarczewska, A and Bielak, K and Zoglowek, A and Sołtys, K and Dobryszycki, P and Ożyhar, A and Różycka, M}, title = {The Role of Intrinsically Disordered Proteins in Liquid-Liquid Phase Separation during Calcium Carbonate Biomineralization.}, journal = {Biomolecules}, volume = {12}, number = {9}, pages = {}, pmid = {36139105}, issn = {2218-273X}, mesh = {Animals ; Biomineralization ; Calcium/metabolism ; Calcium Carbonate ; *Intrinsically Disordered Proteins/metabolism ; Mammals/metabolism ; Otolithic Membrane/metabolism ; Salts ; }, abstract = {Some animal organs contain mineralized tissues. These so-called hard tissues are mostly deposits of calcium salts, usually in the form of calcium phosphate or calcium carbonate. Examples of this include fish otoliths and mammalian otoconia, which are found in the inner ear, and they are an essential part of the sensory system that maintains body balance. The composition of ear stones is quite well known, but the role of individual components in the nucleation and growth of these biominerals is enigmatic. It is sure that intrinsically disordered proteins (IDPs) play an important role in this aspect. They have an impact on the shape and size of otoliths. It seems probable that IDPs, with their inherent ability to phase separate, also play a role in nucleation processes. This review discusses the major theories on the mechanisms of biomineral nucleation with a focus on the importance of protein-driven liquid-liquid phase separation (LLPS). It also presents the current understanding of the role of IDPs in the formation of calcium carbonate biominerals and predicts their potential ability to drive LLPS.}, }
@article {pmid36088585, year = {2022}, author = {Ali, FT and El-Azeem, EMA and Hekal, HFA and El-Gizawy, MM and Sayed, MS and Mandoh, AY and Soliman, AF}, title = {Association of TRPV5, CASR, and CALCR genetic variants with kidney stone disease susceptibility in Egyptians through main effects and gene-gene interactions.}, journal = {Urolithiasis}, volume = {50}, number = {6}, pages = {701-710}, pmid = {36088585}, issn = {2194-7236}, mesh = {Humans ; *Receptors, Calcium-Sensing/genetics/metabolism ; Egypt ; Receptors, Calcitonin/genetics ; Calcium/metabolism ; Polymorphism, Single Nucleotide ; *Kidney Calculi/genetics ; Genetic Predisposition to Disease ; TRPV Cation Channels/genetics ; }, abstract = {Kidney stone disease (KSD) represents an urgent medical problem because of increasing its prevalence. Several functional polymorphisms in genes involved in the renal handling of calcium were associated with KSD pathogenesis. Among those, the rs4236480 of transient receptor potential vanilloid member 5 (TRPV5) gene, the rs1801725 of calcium-sensing receptor (CASR) gene, and the rs1801197 of calcitonin receptor (CALCR) gene appear to be of great importance. Due to the scarce data on the Egyptians, this study aimed to evaluate the association of these candidate genetic variants with the risk of developing KSD in an Egyptian population. To do so, the biochemical parameters were measured along with the genotyping of the three polymorphisms using allelic discrimination assay in 134 KSD patients and 86 age and sex-matched healthy subjects. The results showed that the genotypic distributions and allelic frequencies of the studied variants were significantly different between cases and controls. The three polymorphisms increased the risk of KSD significantly under all the tested genetic models (OR ranges from 2.152 to 5.994), except for the recessive model of the CALCR rs1801197 polymorphism after Bonferroni correction. The gene-gene interaction analyzed by multifactor dimensionality reduction selected the three-locus combination as the best model associated with the susceptibility to KSD with OR 9.706. Further, synergistic interactions were identified between TRPV5 rs4236480 and CALCR rs1801197 variants and CASR rs1801725 and CALCR rs1801197 variants. In conclusion, the TRPV5 rs4236480, CASR rs1801725, and CALCR rs1801197 polymorphisms showed a significant association with the risk of KSD in the Egyptian population. Furthermore, their complex interactions might have an impact on the genetic susceptibility to develop KSD.}, }
@article {pmid36087116, year = {2022}, author = {Guimerà, J and Martínez, A and Bauza, JL and Sanchís, P and Pieras, E and Grases, F}, title = {Effect of phytate on hypercalciuria secondary to bone resorption in patients with urinary stones: pilot study.}, journal = {Urolithiasis}, volume = {50}, number = {6}, pages = {685-690}, pmid = {36087116}, issn = {2194-7236}, mesh = {Humans ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Hypercalciuria/complications ; Phytic Acid/therapeutic use ; Pilot Projects ; Calcium/urine ; Magnesium ; *Bone Resorption/complications ; *Urolithiasis/complications ; *Urinary Calculi/complications ; Biomarkers ; }, abstract = {The objective is to evaluate the effect of phytate supplements on calciuria in patients with urinary stones and elevated bone resorption. The secondary objective is to analyze the therapeutic effect of phytate based on measurements of serum markers of bone resorption. This is a controlled randomized study included patients according to predefined inclusion and exclusion criteria, and randomized them into two groups. Patients in the phytate group received a 380 mg capsule of calcium-magnesium InsP6 (Salvat Laboratories[®]) every 24 h for 3 months and patients in the control group received no treatment. All included patients were male or female, 18-65 years old, had hypercalciuria (> 250 mg/24 h), had a ß-Crosslaps level greater than 0.4 ng/mL, and had bone densitometry results indicative of osteopenia or osteoporosis in the femur and/or spine. At study onset, calciuria was 321 ± 52 mg/24 h in the phytate group and 305 ± 57 mg/24 h in the control group (p > 0.05). At 3 months, calciuria was significantly lower in the phytate group than the control group (226 ± 45 mg/24 h vs. 304 ± 58 mg/24 h, p < 0.05). At study onset, the mean ß-CrossLaps level was 1.25 ± 0.72 ng/mL in the phytate group and 0.57 ± 0.13 ng/mL in the control group (p < 0.05). However, at 3 months, the ß-CrossLaps level was significantly lower in the phytate group than in the control group (0.57 ± 0.13 ng/mL vs. 0.77 ± 0.42 ng/mL, p < 0.05). Phytate reduced calciuria in patients with hypercalciuria secondary to bone resorption. The ß-CrossLaps assay was effective for evaluating the efficacy of phytate on hypercalciuria during follow-up.}, }
@article {pmid35994179, year = {2022}, author = {Chandran, M and Yeh, LTL and de Jong, MC and Bilezikian, JP and Parameswaran, R}, title = {Cognitive deficits in primary hyperparathyroidism - what we know and what we do not know: A narrative review.}, journal = {Reviews in endocrine &amp; metabolic disorders}, volume = {23}, number = {5}, pages = {1079-1087}, pmid = {35994179}, issn = {1573-2606}, mesh = {Animals ; Calcium ; Cognition ; *Cognitive Dysfunction/etiology ; Humans ; *Hyperparathyroidism, Primary/complications ; Parathyroid Hormone/metabolism ; Quality of Life ; }, abstract = {Classic symptoms of primary hyperparathyroidism (PHPT) are seen in approximately 20% of patients. While features such as kidney stones and skeletal disease are often highlighted as directly related to the disease, others can be even more prevalent. For example, cognitive dysfunction and reduced quality of life are common complaints in many patients, even among those who are classified as being asymptomatic. The pathophysiology of PHPT involves the impact of excess parathyroid hormone (PTH) on calcium metabolism. Referencing putative neurocognitive issues, many animal studies have illustrated the potential roles of PTH and PTH receptors in the brain. Functional imaging and pre-and post-parathyroidectomy studies have suggested a link between the neuronal impact of elevated PTH levels on specific functional aspects of the central nervous system, such as cognition. Confounding a direct role for PTH are hypercalcemia and vitamin D deficiency, both of which could conceivably alter CNS function in PHPT. The lack of strong evidence that parathyroidectomy improves cognition in patients with PHPT raises the question as to whether parathyroid surgery should be recommended on this basis alone. This narrative review summarizes the available literature on neurocognitive function in PHPT.}, }
@article {pmid35809664, year = {2022}, author = {Bhardwaj, R and Bhardwaj, A and Dhawan, DK and Tandon, C and Kaur, T}, title = {4-PBA rescues hyperoxaluria induced nephrolithiasis by modulating urinary glycoproteins: Cross talk between endoplasmic reticulum, calcium homeostasis and mitochondria.}, journal = {Life sciences}, volume = {305}, number = {}, pages = {120786}, doi = {10.1016/j.lfs.2022.120786}, pmid = {35809664}, issn = {1879-0631}, mesh = {Animals ; Butylamines ; Calcium/metabolism ; Calnexin/metabolism/pharmacology ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress ; Glycoproteins/metabolism ; Homeostasis ; *Hyperoxaluria ; *Kidney Calculi/etiology/metabolism ; Mitochondria/metabolism ; Molecular Chaperones/metabolism ; Rats ; }, abstract = {AIM: Urinary glycoproteins such as Tamm Horsfall Protein (THP) and Osteopontin (OPN) are well established key regulators of renal stone formation. Additionally, recent revelations have highlighted the influence of Endoplasmic Reticulum (ER) and mitochondria of crucial importance in nephrolithiasis. However, till date conclusive approach highlighting the influence of ER stress on urinary glycoproteins and chaperone in nephrolithiasis remains elusive. Therefore, the present study was focussed on deciphering the possible effect of 4-PBA mitigating ER stress on urinary glycoproteins and calnexin (chaperone) with emphasis on interlinking calcium homeostasis in hyperoxaluric rats.<br><br>MATERIAL AND METHODS: Post 9&#xa0;days of treatment, animals were sacrificed, and renal tissues were investigated for urinary glycoproteins, calnexin, calcium homeostasis, ER environment, redox status, and mitochondrial linkage.<br><br>KEY FINDINGS: 4-PBA appreciably reversed the altered levels of THP, OPN, and calnexin observed along with curtailing the disrupted calcium homeostasis when assessed for SERCA activity and intra-cellular calcium levels. Additionally, significant improvement in the perturbed ER environment as verified by escalated ER stress markers, disturbed protein folding-aggregation-degradation (congo red assay) pathway, and redox status was found post 4-PBA intervention. Interestingly, linkage of ER stress and mitochondria was established under hyperoxaluric conditions when assessed for protein levels of VDAC1 and GRP75.<br><br>SIGNIFICANCE: 4-PBA treatment resulted in rectifying the repercussions of ER-mitochondrial caused distress when assessed for protein folding/aggregation/degradation events along with disturbed calcium homeostasis. The present study advocates the necessity to adopt a holistic vision towards hyperoxaluria with emphasis on glycoproteins and ER environment.}, }
@article {pmid35768889, year = {2022}, author = {Aliberti, L and Gagliardi, I and Gamberini, MR and Ziggiotto, A and Verrienti, M and Carnevale, A and Bondanelli, M and Zatelli, MC and Ambrosio, MR}, title = {Beta-thalassaemia major: Prevalence, risk factors and clinical consequences of hypercalciuria.}, journal = {British journal of haematology}, volume = {198}, number = {5}, pages = {903-911}, pmid = {35768889}, issn = {1365-2141}, mesh = {Adult ; Calcium ; Female ; Humans ; Hypercalciuria/epidemiology/etiology/urine ; *Kidney Calculi/urine ; Prevalence ; Risk Factors ; *beta-Thalassemia/complications/drug therapy ; }, abstract = {Regular transfusion and chelation therapy produces increased life expectancy in thalassaemic patients who may develop new complications. Since few data are available regarding hypercalciuria in β-thalassaemia major (TM), the aim of our study was to evaluate its prevalence, risk factors and clinical consequences. We enrolled 176 adult TM patients followed at the Center of Thalassemia of Ferrara. Hypercalciuria was defined by a calciuria of 4 mg/kg/day or more in a 24-h urine sample. Anamnestic, biochemical and radiological data were collected. Hypercalciuria prevalence was reported in 69.3% of patients (females 52.5%). Hypercalciuric (HC) patients used deferasirox (DFX) more often than normocalciuric (NC) patients (47.5% vs 29.6%; p < 0.05). In HC subjects plasma parathyroid hormone (PTH) (24.1 ± 10.4 vs 30.1 ± 13.2 pg/ml) and phosphate levels (3.6 ± 0.5 vs 3.8 ± 0.7 mg/dl) were lower, whereas serum calcium (9.6 ± 0.4 vs 9.4 ± 0.4 mg/dl) and urinary 24-h phosphaturia (0.9 ± 0.4 vs 0.6 ± 0.3 g/day) were higher as compared to NC patients (p < 0.05 for all comparisons). Supplementation with oral calcium and cholecalciferol was similar between the groups. A higher rate of kidney stones was present in HC (14.8%) versus NC patients (3.7%) (p < 0.05). Hypercalciuria is a frequent complication in adequately treated adult TM patients. Hypercalciuria prevalence is increased in DFX users whereas haemoglobin level or calcium supplements play no role. A significant proportion of HC patients developed kidney stones.}, }
@article {pmid35577790, year = {2022}, author = {Lee, Y and Wiriyasermkul, P and Kongpracha, P and Moriyama, S and Mills, DJ and Kühlbrandt, W and Nagamori, S}, title = {Ca[2+]-mediated higher-order assembly of heterodimers in amino acid transport system b[0,+] biogenesis and cystinuria.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {2708}, pmid = {35577790}, issn = {2041-1723}, mesh = {Amino Acid Transport Systems/metabolism ; *Amino Acid Transport Systems, Basic/metabolism/ultrastructure ; *Calcium/chemistry/metabolism ; Cystine/metabolism ; *Cystinuria/genetics/metabolism ; Humans ; }, abstract = {Cystinuria is a genetic disorder characterized by overexcretion of dibasic amino acids and cystine, causing recurrent kidney stones and kidney failure. Mutations of the regulatory glycoprotein rBAT and the amino acid transporter b[0,+]AT, which constitute system b[0,+], are linked to type I and non-type I cystinuria respectively and they exhibit distinct phenotypes due to protein trafficking defects or catalytic inactivation. Here, using electron cryo-microscopy and biochemistry, we discover that Ca[2+] mediates higher-order assembly of system b[0,+]. Ca[2+] stabilizes the interface between two rBAT molecules, leading to super-dimerization of b[0,+]AT-rBAT, which in turn facilitates N-glycan maturation and protein trafficking. A cystinuria mutant T216M and mutations of the Ca[2+] site of rBAT cause the loss of higher-order assemblies, resulting in protein trapping at the ER and the loss of function. These results provide the molecular basis of system b[0,+] biogenesis and type I cystinuria and serve as a guide to develop new therapeutic strategies against it. More broadly, our findings reveal an unprecedented link between transporter oligomeric assembly and protein-trafficking diseases.}, }
@article {pmid35574616, year = {2022}, author = {Schlaht, KM and Sas, DJ and Davis, DMR and Hand, JL}, title = {An investigation of metabolic disturbances, including urinary stone disease, hypothyroidism, and osteoporosis in basal cell nevus syndrome.}, journal = {Pediatric dermatology}, volume = {39}, number = {5}, pages = {713-717}, doi = {10.1111/pde.15022}, pmid = {35574616}, issn = {1525-1470}, mesh = {Adult ; *Basal Cell Nevus Syndrome/complications ; Child ; Humans ; *Hypothyroidism/complications/epidemiology ; *Osteoporosis/complications/epidemiology ; Retrospective Studies ; *Skin Neoplasms/diagnosis ; *Urinary Calculi/complications ; *Urologic Diseases ; }, abstract = {BACKGROUND/OBJECTIVES: Basal cell nevus syndrome (BCNS) is an autosomal dominant skin cancer predisposition syndrome associated with abnormal mineral metabolism, a risk factor for urinary stone disease (USD). However, no research investigating the association between BCNS and USD or other manifestations of abnormal mineral metabolism has been conducted. The objective of this study is to investigate the association between BCNS and conditions associated with disordered mineral metabolism including USD, hypothyroidism, and osteoporosis and compare them to prevalence in the general population to elucidate potential unknown manifestations of the condition.<br><br>METHODS: This retrospective study examined medical records of adult and pediatric patients with confirmed BCNS from the Mayo Clinic database from 1 January 1995 to 12 January 2020. Records were surveyed for evidence of USD and other comorbidities potentially related to BCNS. The studied cohort included 100 adult patients and 5 pediatric patients.<br><br>RESULTS: A total of 105 patients were included in this analysis, 10 of whom experienced confirmed USD, representing a prevalence of 10%. Six adult patients were identified with a diagnosis of osteoporosis, representing a prevalence of 6%. Thirteen adult patients were identified with a diagnosis of hypothyroidism, representing a prevalence of 13%.<br><br>CONCLUSIONS: This study identified a prevalence of USD in BCNS patients comparable to estimates of national prevalence, indicating that known abnormalities in mineral metabolism likely do not increase the incidence of USD in BCNS patients. Additional findings included increased prevalence of hypothyroidism and decreased prevalence of osteoporosis in the BCNS cohort compared to national averages.}, }
@article {pmid35514354, year = {2022}, author = {Tamma, G and Di Mise, A and Ranieri, M and Centrone, M and Venneri, M and D'Agostino, M and Ferrulli, A and Šimunič, B and Narici, M and Pisot, R and Valenti, G}, title = {Early Biomarkers of Altered Renal Function and Orthostatic Intolerance During 10-day Bedrest.}, journal = {Frontiers in physiology}, volume = {13}, number = {}, pages = {858867}, pmid = {35514354}, issn = {1664-042X}, abstract = {Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. We report here that 10 days of inactivity are associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity.}, }
@article {pmid35485213, year = {2022}, author = {Puliani, G and Hasenmajer, V and Simonelli, I and Sada, V and Pofi, R and Minnetti, M and Cozzolino, A and Napoli, N and Pasqualetti, P and Gianfrilli, D and Isidori, AM}, title = {Safety and Efficacy of PTH 1-34 and 1-84 Therapy in Chronic Hypoparathyroidism: A Meta-Analysis of Prospective Trials.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {37}, number = {7}, pages = {1233-1250}, pmid = {35485213}, issn = {1523-4681}, mesh = {*Calcium ; Humans ; *Hypoparathyroidism ; Parathyroid Hormone/adverse effects ; Phosphates ; Prospective Studies ; Quality of Life ; Vitamin D ; }, abstract = {Hypoparathyroidism is the only endocrine deficiency for which hormone replacement therapy is not the standard of care. Although conventional treatments may control hypocalcaemia, other complications such as hyperphosphatemia, kidney stones, peripheral calcifications, and bone disease remain unmet needs. This meta-analysis (PROSPERO registration number CRD42019126881) aims to evaluate and compare the efficacy and safety of PTH1-34 and PTH1-84 in restoring calcium metabolism in chronic hypoparathyroidism. EMBASE, PubMed, and CENTRAL databases were searched for randomized clinical trials or prospective studies published between January 1996 and March 2021. English-language trials reporting data on replacement with PTH1-34 or PTH1-84 in chronic hypoparathyroidism were selected. Three authors extracted outcomes, one author performed quality control, all assessed the risk of biases. Overall, data from 25 studies on 588 patients were analyzed. PTH therapy had a neutral effect on calcium levels, while lowering serum phosphate (-0.21 mmol/L; 95% confidence interval [CI], -0.31 to -0.11 mmol/L; p < 0.001) and urinary calcium excretion (-1.21 mmol/24 h; 95% CI, -2.03 to -0.41 mmol/24 h; p = 0.003). Calcium phosphate product decreased under PTH1-84 therapy only. Both treatments enabled a significant reduction in calcium and calcitriol supplementation. PTH therapy increased bone turnover markers and lumbar spine mineral density. Quality of life improved and there was no difference in the safety profile between PTH and conventionally treated patients. Results for most outcomes were similar for the two treatments. Limitations of the study included considerable population overlap between the reports, incomplete data, and heterogeneity in the protocol design. In conclusion, the meta-analysis of data from the largest collection to date of hypoparathyroid patients shows that PTH therapy is safe, well-tolerated, and effective in normalizing serum phosphate and urinary calcium excretion, as well as enabling a reduction in calcium and vitamin D use and improving quality of life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).}, }
@article {pmid35274705, year = {2023}, author = {Esper, PLG and Rodrigues, FG and Melo, TL and Ormanji, MS and Campos, CM and Alvarenga, JC and Caparbo, VF and Carvalho, AB and Pereira, RMR and Heilberg, IP}, title = {Bone density, microarchitecture and estimated strength in stone formers: a cross-sectional HR-pQCT study.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {38}, number = {2}, pages = {425-434}, doi = {10.1093/ndt/gfac128}, pmid = {35274705}, issn = {1460-2385}, mesh = {Female ; Male ; Humans ; Adult ; Bone Density ; Cross-Sectional Studies ; Calcium ; *Bone Diseases, Metabolic ; *Kidney Calculi ; Absorptiometry, Photon ; }, abstract = {BACKGROUND: Low areal bone mineral density (BMD), increased fracture risk and altered bone remodeling have been described among stone formers (SFs), but the magnitude of these findings differs by age, sex, menopausal status and urinary calcium (uCa). This study aimed to investigate volumetric BMD (vBMD), bone microarchitecture and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in young SFs, irrespective of calciuria, further distinguishing trabecular from cortical compartments.<br><br>METHODS: HR-pQCT/FEA was performed at the distal tibia (DT) and distal radius (DR) in 106 SFs (57 males and 49 premenopausal females; median age 37 years) and compared with 106 non-SFs (NSFs) retrieved from an existing database, matched for age, sex and body mass index (BMI). Biochemical/hormonal serum and urinary parameters were obtained from SFs.<br><br>RESULTS: SFs exhibited significantly lower trabecular number (TbN) and higher trabecular separation (TbSp) than NSFs at both anatomical sites and lower cortical porosity in the DR. In a subgroup analysis separated by sex, female SFs presented significantly lower TbvBMD, relative bone volume fraction (BV/TV) and TbN and higher TbSp than NSFs at both sites, while male SFs showed significantly lower stiffness and failure load. Multivariate analysis showed TbN to be independently associated with sex and BMI at both sites and with uCa at the DR.<br><br>CONCLUSIONS: The present findings suggest that bone disease represents an early event among SFs, associated at least in part with calcium excretion and mainly characterized by trabecular bone microarchitecture impairment, especially among women, but with reduced bone strength parameters in men.}, }
@article {pmid35274024, year = {2022}, author = {Li, LS and Zhu, YP and Xia, QD and Wang, SG and He, D}, title = {High-Calcium Microenvironment during the Development of Kidney Calculi Can Promote Phenotypic Transformation of NRK-52E Cells by Inhibiting the Expression of Stromal Interaction Molecule-1.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {2350198}, pmid = {35274024}, issn = {2314-6141}, mesh = {Apoptosis ; *Calcium/metabolism ; Cell Line ; Epithelial Cells/metabolism ; Humans ; *Kidney Calculi ; Phenotype ; }, abstract = {OBJECTIVE: To explore whether Stromal Interaction Molecule-1 (STIM1) participates in the phenotypic transformation of NRK-52E cells under high-calcium microenvironment.<br><br>MATERIALS AND METHODS: NRK-52E cells were treated with high concentration of calcium. The viability and apoptosis of cells were detected by CCK-8 (cell counting kit-8) and flow cytometry, respectively. The expression changes of phenotypic marker proteins (E-cadherin and OPN) and calcium channel proteins (STIMl and Orai1) in high-calcium environment were detected by western blotting and real-time quantitative polymerase chain reaction. The expression of STIMl protein in NRK-52E cells was upregulated and downregulated by plasmid-STIM1 and plasmid-shRNA-STIMl, respectively. The expressions of phenotypic marker proteins after upregulation or downregulation of STIMl were detected again. Besides, the intracellular calcium concentrations of NRK-52E cells in different treatments were detected by flow cytometry.<br><br>RESULTS: High-calcium microenvironment can promote the phenotypic transformation and the adhesion of calcium salts in NRK-52E cells and simultaneously suppress the expression of STIMl protein in NRK-52E cells. Downregulation of STIMl protein could also promote the phenotype transformation, while both the gene silence of matrix gla protein (MGP) and overexpression of STIMl showed reverse results.<br><br>CONCLUSION: STIMl protein plays an important role in promoting phenotypic transformation of NRK-52E cells in high-calcium microenvironment.}, }
@article {pmid35084652, year = {2022}, author = {Negri, AL and Del Valle, EE}, title = {Role of claudins in idiopathic hypercalciuria and renal lithiasis.}, journal = {International urology and nephrology}, volume = {54}, number = {9}, pages = {2197-2204}, pmid = {35084652}, issn = {1573-2584}, mesh = {Calcium/metabolism ; Claudin-2 ; Claudins/genetics/metabolism ; Humans ; Hypercalciuria/genetics ; *Kidney Calculi/genetics ; *Lithiasis ; }, abstract = {Paracellular transport in the kidney is mediated by a family of proteins located in the tight junctions called claudins which confers its ionic selectivity. Claudin-2 is highly expressed in the proximal tubule and descending limb of Henle and mediate paracellular reabsorption of sodium and calcium cations. In the thick ascending limb of Henle (TALH) calcium is reabsorbed by a paracellular channel formed by Claudin-16 and-19. Claudin-16 mediates cationic permeability while Claudin-19 increases the cationic selectivity of Claudin-16 by blocking anionic permeability. On the other hand, Claudin 14, that is also located in TALH, inhibits the paracellular permeability of Claudin-16 to calcium. Recent wide genomic association analysis studies have detected four common synonymous variants (genetic polymorphisms of a single nucleotide, SNPs) at the locus of Claudin-14 gene that were significantly associated with the presence of renal lithiasis. Another study of wide genomic association and nephrolithiasis was carried out in the general population but including chromosome X, where claudin-2 gene is located. They detected nine SNPs that had a significant association with renal lithiasis risk. A greater knowledge of the paracellular pathway controlled by claudins and its regulation will allow us to develop future new treatments for idiopathic hypercalciuria and renal lithiasis.}, }
@article {pmid35008629, year = {2021}, author = {Flisiński, M and Brymora, A and Skoczylas-Makowska, N and Stefańska, A and Manitius, J}, title = {Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008629}, issn = {1422-0067}, mesh = {Animals ; *Diet ; Eating ; Electrolytes/urine ; Fructose ; Kidney Tubules/*injuries/pathology ; Male ; Metabolic Syndrome/blood/*etiology/urine ; Nutritional Status ; Rats, Wistar ; Risk Factors ; Urinalysis ; Urolithiasis/blood/*etiology/urine ; }, abstract = {Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)-regular diet with a FR < 3%; F10 (n = 6)-regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)-60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.}, }
@article {pmid34967159, year = {2021}, author = {Smirnova, VI and Lebedev, DG and Lapin, SV and Emanuel, VL and E, RV}, title = {[Analysis of urinary stone composition by infrared spectroscopy in the population of the European part of Russia].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {6}, pages = {20-24}, pmid = {34967159}, issn = {1728-2985}, mesh = {Calcium Oxalate ; Humans ; *Kidney Calculi ; Spectrum Analysis ; *Urinary Calculi/epidemiology ; *Urolithiasis ; }, abstract = {INTRODUCTION: Urolithiasis is one of the most common urological diseases, which affect at least 3% of the population.<br><br>AIM: To study the epidemiology of urolithiasis in the European part of the Russian Federation and to determine the composition of urinary stones in order to understand the pathogenetic mechanisms of urinary stones formation.<br><br>MATERIALS AND METHODS: Urinary stone were obtained from 2888 patients with urolithiasis and the composition of kidney stones was analyzed using the method of infrared spectroscopy.<br><br>RESULTS: The predominance of oxalate stones was seen in kidney stones with mixed composition (83%) and the prevalence of uric acid stones (54%) was revealed in "pure" kidney stones. Urinary stones with a predominance of oxalates had significantly less impurities (12,4%) than stones with a predominance of uric acid, phosphates and carbonates with average amount of impurities more than 24%. Conslusion. The analysis of stone composition with a consideration of pathogenic factor showed that disorders of calcium metabolism in the population of the European part of the Russian Federation prevailed (88%).}, }
@article {pmid34959951, year = {2021}, author = {Stone, MS and Martin, BR and Weaver, CM}, title = {Short-Term Supplemental Dietary Potassium from Potato and Potassium Gluconate: Effect on Calcium Retention and Urinary pH in Pre-Hypertensive-to-Hypertensive Adults.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34959951}, issn = {2072-6643}, mesh = {Adult ; Aged ; Aged, 80 and over ; Calcium/*metabolism/*urine ; Calcium, Dietary/administration &amp; dosage ; Cross-Over Studies ; *Dietary Supplements ; Female ; Gluconates/*administration &amp; dosage ; Humans ; Hydrogen-Ion Concentration ; Hypertension/*metabolism/urine ; Male ; Middle Aged ; Potassium, Dietary/*administration &amp; dosage ; *Solanum tuberosum ; Young Adult ; }, abstract = {Potassium supplementation has been associated with reduced urinary calcium (Ca) excretion and increased Ca balance. Dietary interventions assessing the impact of potassium on bone are lacking. In this secondary analysis of a study designed primarily to determine blood pressure effects, we assessed the effects of potassium intake from potato sources and a potassium supplement on urinary Ca, urine pH, and Ca balance. Thirty men (n = 15) and women (n = 15) with a mean ± SD age and BMI of 48.2 ± 15 years and 31.4 ± 6.1 kg/m[2], respectively, were enrolled in a cross-over, randomized control feeding trial. Participants were assigned to a random order of four 16-day dietary potassium interventions including a basal diet (control) of 2300 mg/day (~60 mmol/day) of potassium, and three phases of an additional 1000 mg/day (3300 mg/day(~85 mmol/day) total) of potassium in the form of potatoes (baked, boiled, or pan-heated), French fries (FF), or a potassium (K)-gluconate supplement. Calcium intake for all diets was approximately 700-800 mg/day. Using a mixed model ANOVA there was a significantly lower urinary Ca excretion in the K-gluconate phase (96 ± 10 mg/day) compared to the control (115 ± 10 mg/day; p = 0.027) and potato (114 ± 10 mg/day; p = 0.033). In addition, there was a significant difference in urinary pH between the supplement and control phases (6.54 ± 0.16 vs. 6.08 ± 0.18; p = 0.0036). There were no significant differences in Ca retention. An increased potassium intake via K-gluconate supplementation may favorably influence urinary Ca excretion and urine pH. This trial was registered at ClinicalTrials.gov as NCT02697708.}, }
@article {pmid34959915, year = {2021}, author = {Bargagli, M and Ferraro, PM and Vittori, M and Lombardi, G and Gambaro, G and Somani, B}, title = {Calcium and Vitamin D Supplementation and Their Association with Kidney Stone Disease: A Narrative Review.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34959915}, issn = {2072-6643}, mesh = {Bone and Bones/metabolism ; Calcium/administration &amp; dosage/*adverse effects/metabolism ; Dietary Supplements/*adverse effects ; Humans ; Hypercalciuria ; Intestines ; Kidney Calculi/*etiology/metabolism/prevention &amp; control ; Minerals/metabolism ; Oxalates/metabolism ; Risk ; Vitamin D/administration &amp; dosage/*adverse effects ; Vitamin D3 24-Hydroxylase/genetics ; }, abstract = {Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although different monogenic polymorphisms have been proposed as playing a causal role for calcium nephrolithiasis, the prevalence of these mutations in the general population and their complete pathogenetic pathway is yet to be determined. General dietary advice for kidney stone formers includes elevated fluid intake, dietary restriction of sodium and animal proteins, avoidance of a low calcium diet, maintenance of a normal body mass index, and elevated intake of vegetables and fibers. Thus, balanced calcium consumption protects against the risk for kidney stones by reducing intestinal oxalate availability and its urinary excretion. However, calcium supplementation given between meals might increase urinary calcium excretion without the beneficial effect on oxalate. In kidney stone formers, circulating active vitamin D has been found to be increased, whereas higher plasma 25-hydroxycholecalciferol seems to be present only in hypercalciuric patients. The association between nutritional vitamin D supplements and the risk for stone formation is currently not completely understood. However, taken together, available evidence might suggest that vitamin D administration worsens the risk for stone formation in patients predisposed to hypercalciuria. In this review, we analyzed and discussed available literature on the effect of calcium and vitamin D supplementation on the risk for kidney stone formation.}, }
@article {pmid34435888, year = {2022}, author = {Xun, Y and Zhou, P and Yang, Y and Li, C and Zhang, J and Hu, H and Qin, B and Zhang, Z and Wang, Q and Lu, Y and Wang, S}, title = {Role of Nox4 in High Calcium-Induced Renal Oxidative Stress Damage and Crystal Deposition.}, journal = {Antioxidants &amp; redox signaling}, volume = {36}, number = {1-3}, pages = {15-38}, doi = {10.1089/ars.2020.8159}, pmid = {34435888}, issn = {1557-7716}, mesh = {Animals ; *Calcium/metabolism ; Kidney/metabolism ; NADPH Oxidase 4/metabolism ; *Oxidative Stress ; Rats ; Reactive Oxygen Species/metabolism ; }, abstract = {Aims: We aimed at exploring the role of nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (Nox4) in the regulation of hypercalciuria-induced renal oxidative damage and crystal depositions. Results: High calcium activated Nox4 expression through protein kinase C (PKC). Downregulation of Nox4 expression attenuated hypercalciuria-induced osteoblast-associated protein expression, oxidative stress injury, and crystal deposition in rat kidneys of 1,25-dihydroxyvitamin D3 (VitD) urolithiasis model. Further, calcium-induced activation of mitogen-activated protein kinase (MAPK), overexpression of osteoblast-associated protein, oxidative stress injury, apoptosis, and calcium salt deposition in normal rat kidney epithelial-like (NRK-52E) cells were reversed by downregulating Nox4 expression but were enhanced by upregulating Nox4 expression in vitro. Moreover, calcium-induced increases of osteoblast-associated protein expression were attenuated by the c-Jun-N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) inhibitors. Innovation: Our results demonstrated the effect of Nox4 in the pathological process of kidney stones in in vitro and in vivo studies for the first time. Calcium aggravates renal oxidative stress injury and crystal deposition by activating the Nox4-related reactive oxygen species (ROS)-ERK/JNK pathway in the rat kidney. This study is expected to provide a new theoretical basis for the prevention and treatment of kidney stones. Conclusion: Nox4-derived ROS induced by calcium through PKC caused oxidative stress damage and apoptosis in renal tubular epithelial cells; in addition, Nox4-derived ROS induced by calcium mediated abnormal activation of the bone morphogenetic protein 2 (BMP2) signaling pathway through the MAPK signaling pathway, which induced renal tubular epithelial cells to transdifferentiate into osteoblast-like cells, resulting in the formation of a kidney stone. Antioxid. Redox Signal. 36, 15-38.}, }
@article {pmid34406326, year = {2021}, author = {van Rosendael, AR and van den Hoogen, IJ and Gianni, U and Ma, X and Tantawy, SW and Bax, AM and Lu, Y and Andreini, D and Al-Mallah, MH and Budoff, MJ and Cademartiri, F and Chinnaiyan, K and Choi, JH and Conte, E and Marques, H and de Araújo Gonçalves, P and Gottlieb, I and Hadamitzky, M and Leipsic, JA and Maffei, E and Pontone, G and Shin, S and Kim, YJ and Lee, BK and Chun, EJ and Sung, JM and Lee, SE and Virmani, R and Samady, H and Sato, Y and Stone, PH and Berman, DS and Narula, J and Blankstein, R and Min, JK and Lin, FY and Shaw, LJ and Bax, JJ and Chang, HJ}, title = {Association of Statin Treatment With Progression of Coronary Atherosclerotic Plaque Composition.}, journal = {JAMA cardiology}, volume = {6}, number = {11}, pages = {1257-1266}, pmid = {34406326}, issn = {2380-6591}, mesh = {Calcium/*metabolism ; Coronary Artery Disease/diagnosis/*drug therapy ; Coronary Vessels/*diagnostic imaging/metabolism ; Disease Progression ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Male ; Middle Aged ; Plaque, Atherosclerotic/diagnosis/*drug therapy ; Risk Factors ; Tomography, X-Ray Computed ; }, abstract = {IMPORTANCE: The density of atherosclerotic plaque forms the basis for categorizing calcified and noncalcified morphology of plaques.<br><br>OBJECTIVE: To assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression.<br><br>This cohort study enrolled 857 patients who underwent serial coronary computed tomography angiography 2 or more years apart and had quantitative measurements of coronary plaques throughout the entire coronary artery tree. The study was conducted from 2013 to 2016 at 13 sites in 7 countries.<br><br>MAIN OUTCOMES AND MEASURES: The main outcome was progression of plaque composition of individual coronary plaques. Six plaque composition types were defined on a voxel-level basis according to the plaque attenuation (expressed in Hounsfield units [HU]): low attenuation (-30 to 75 HU), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU). The progression rates of these 6 compositional plaque types were evaluated according to the interaction between statin use and baseline plaque volume, adjusted for risk factors and time interval between scans. Plaque progression was also examined based on baseline calcium density. Analysis was performed among lesions matched at baseline and follow-up. Data analyses were conducted from August 2019 through March 2020.<br><br>RESULTS: In total, 2458 coronary lesions in 857 patients (mean [SD] age, 62.1 [8.7] years; 540 [63.0%] men; 548 [63.9%] received statin therapy) were included. Untreated coronary lesions increased in volume over time for all 6 compositional types. Statin therapy was associated with volume decreases in low-attenuation plaque (&#x3b2;, -0.02; 95% CI, -0.03 to -0.01; P&#x2009;=&#x2009;.001) and fibro-fatty plaque (&#x3b2;, -0.03; 95% CI, -0.04 to -0.02; P&#x2009;<&#x2009;.001) and greater progression of high-density calcium plaque (&#x3b2;, 0.02; 95% CI, 0.01-0.03; P&#x2009;<&#x2009;.001) and 1K plaque (&#x3b2;, 0.02; 95% CI, 0.01-0.03; P&#x2009;<&#x2009;.001). When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, statin therapy was not associated with a change in overall calcified plaque volume (&#x3b2;, -0.03; 95% CI, -0.08 to 0.02; P&#x2009;=&#x2009;.24) but was associated with a transformation toward more dense calcium. Interaction analysis between baseline plaque volume and calcium density showed that more dense coronary calcium was associated with less plaque progression.<br><br>CONCLUSIONS AND RELEVANCE: The results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium. A pattern of slower overall plaque progression was observed with increasing density. All findings support the concept of reduced atherosclerotic risk with increased densification of calcium.}, }
@article {pmid34281258, year = {2021}, author = {Grahl, MVC and Uberti, AF and Broll, V and Bacaicoa-Caruso, P and Meirelles, EF and Carlini, CR}, title = {Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity.}, journal = {International journal of molecular sciences}, volume = {22}, number = {13}, pages = {}, pmid = {34281258}, issn = {1422-0067}, mesh = {Amino Acid Sequence ; Animals ; Calcium/metabolism ; Cell Line ; Cell Nucleus/metabolism ; HEK293 Cells ; Humans ; In Vitro Techniques ; Mice ; Microglia/drug effects/metabolism/microbiology ; Models, Molecular ; Neurons/drug effects/metabolism/microbiology ; Neurotoxins/chemistry/metabolism/toxicity ; Nuclear Localization Signals ; Platelet Aggregation/drug effects ; Proteus mirabilis/*enzymology/*pathogenicity ; Recombinant Proteins/chemistry/metabolism/toxicity ; Urease/chemistry/*metabolism/*toxicity ; Virulence/physiology ; }, abstract = {Infection by Proteus mirabilis causes urinary stones and catheter incrustation due to ammonia formed by urease (PMU), one of its virulence factors. Non-enzymatic properties, such as pro-inflammatory and neurotoxic activities, were previously reported for distinct ureases, including that of the gastric pathogen Helicobacter pylori. Here, PMU was assayed on isolated cells to evaluate its non-enzymatic properties. Purified PMU (nanomolar range) was tested in human (platelets, HEK293 and SH-SY5Y) cells, and in murine microglia (BV-2). PMU promoted platelet aggregation. It did not affect cellular viability and no ammonia was detected in the cultures' supernatants. PMU-treated HEK293 cells acquired a pro-inflammatory phenotype, producing reactive oxygen species (ROS) and cytokines IL-1β and TNF-α. SH-SY5Y cells stimulated with PMU showed high levels of intracellular Ca[2+] and ROS production, but unlike BV-2 cells, SH-SY5Y did not synthesize TNF-α and IL-1β. Texas Red-labeled PMU was found in the cytoplasm and in the nucleus of all cell types. Bioinformatic analysis revealed two bipartite nuclear localization sequences in PMU. We have shown that PMU, besides urinary stone formation, can potentially contribute in other ways to pathogenesis. Our data suggest that PMU triggers pro-inflammatory effects and may affect cells beyond the renal system, indicating a possible role in extra-urinary diseases.}, }
@article {pmid34214114, year = {2021}, author = {Kwiatkowska, B and Bisiecka, A and Pawelec, &#x141; and Witek, A and Witan, J and Nowakowski, D and Konczewski, P and Biel, R and Król, K and Martewicz, K and Lissek, P and Vařeka, P and Lipowicz, A}, title = {Differential diagnosis of a calcified cyst found in an 18th century female burial site at St. Nicholas Church cemetery (Libkovice, Czechia).}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0254173}, pmid = {34214114}, issn = {1932-6203}, mesh = {Bone and Bones/metabolism/pathology ; Burial/methods ; Calcium/metabolism ; Cemeteries ; Cysts/*diagnosis/metabolism/*pathology ; Czech Republic ; Diagnosis, Differential ; Female ; Fetus/metabolism/pathology ; Humans ; Middle Aged ; }, abstract = {During archaeological excavations in burial sites, sometimes stoned organic objects are found, in addition to human remains. Those objects might be of a different origin, depending on various factors influencing members of a community (i.e. diseases, trauma), which provides information about their living conditions. The St. Nicholas Church archaeological site (Libkovice, Czechia) in the 18th century horizon of the cemetery, yielded a maturus-senilis female skeleton with a stone object in the left iliac fossa. This object was an oviform cyst-like rough structure, measuring 54 mm in length, 35 mm in maximum diameter and 0.2-0.7 mm shell thickness. Within the object there were small fetal bones (long bones, i.e. femur and two tibias, two scapulas, three ribs, vertebrae and other tiny bone fragments). Methods utilized to analyze the outer and inner surface morphology of the cyst and its inside, included: X-ray, CT imaging, SEM, histological staining and EDS. The EDS analysis revealed the presence of primarily oxygen, calcium and phosphorus in bone samples, and oxygen and silicon, in stone shell. Based on the length of the femur (20.2 mm) and tibia (16 mm) shafts, the fetal age was determined as being in the 15-18 week of pregnancy. The differential diagnosis was conducted, including for the three most probable cases: fetiform teratoma (FT), fetus-in-fetu (FIF) and lithopedion. The possibility of fetiform teratoma was discounted due to the presence of an anatomically correct spine, long bones and the proportions of the find. Although the low calcium content in the shell (2.3% atom mass), the lack of skull bones and the better developed lower limbs indicate fetus-in-fetu rather than lithopedion, the analyses results are unable to conclusively identify the object under one of these two categories since there are insufficient such cases in excavation material with which to draw comparison.}, }
@article {pmid34152561, year = {2022}, author = {Bargagli, M and Moochhala, S and Robertson, WG and Gambaro, G and Lombardi, G and Unwin, RJ and Ferraro, PM}, title = {Urinary metabolic profile and stone composition in kidney stone formers with and without heart disease.}, journal = {Journal of nephrology}, volume = {35}, number = {3}, pages = {851-857}, pmid = {34152561}, issn = {1724-6059}, mesh = {Calcium/metabolism ; Citrates ; Citric Acid ; *Diabetes Mellitus ; *Heart Diseases ; Humans ; *Hypertension ; *Kidney Calculi/epidemiology/metabolism ; Magnesium ; Metabolome ; }, abstract = {OBJECTIVE: Kidney stone disease seems to be associated with an increased risk of incident cardiovascular outcomes; the aim of this study is to identify differences in 24-h urine excretory profiles and stone composition among stone formers with and without cardiovascular disease (CVD).<br><br>METHODS: Data from patients attending the Department of Renal Medicine's metabolic stone clinic from 1995 to 2012 were reviewed. The sample was divided according to the presence or absence of CVD (myocardial infarction, angina, coronary revascularization, or surgery for calcified heart valves). Univariable and multivariable regression models, adjusted for age, sex, BMI, hypertension, diabetes, eGFR, plasma bicarbonate and potential renal acid load of foods were used to investigate differences across groups.<br><br>RESULTS: 1826 patients had available data for 24-h urine analysis. Among these, 108 (5.9%) had a history of CVD. Those with CVD were older, have higher prevalence of hypertension and diabetes and lower eGFR. Univariable analysis showed that patients with CVD had significantly lower 24-h urinary excretions for citrate (2.4 vs 2.6 mmol/24 h, p = 0.04), magnesium (3.9 vs 4.2 mmol/24 h, p = 0.03) and urinary pH (6.1 vs 6.2, p = 0.02). After adjustment for confounders, differences in urinary citrate and magnesium excretions remained significant. No differences in the probability of stone formation or stone compositions were found.<br><br>CONCLUSIONS: Stone formers with CVD have lower renal alkali excretion, possibly suggesting higher acid retention in stone formers with cardiovascular comorbidities. Randomized clinical trials including medications and a controlled diet design are needed to confirm the results presented here.}, }
@article {pmid34054913, year = {2021}, author = {Litvinova, MM and Khafizov, K and Korchagin, VI and Speranskaya, AS and Asanov, AY and Matsvay, AD and Kiselev, DA and Svetlichnaya, DV and Nuralieva, SZ and Moskalev, AA and Filippova, TV}, title = {Association of CASR, CALCR, and ORAI1 Genes Polymorphisms With the Calcium Urolithiasis Development in Russian Population.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {621049}, pmid = {34054913}, issn = {1664-8021}, abstract = {Kidney stone disease is an urgent medical and social problem. Genetic factors play an important role in the disease development. This study aims to establish an association between polymorphisms in genes coding for proteins involved in calcium metabolism and the development of calcium urolithiasis in Russian population. In this case-control study, we investigated 50 patients with calcium urolithiasis (experimental group) and 50 persons lacking signs of kidney stone disease (control group). For molecular genetic analysis we used a previously developed gene panel consisting of 33 polymorphisms in 15 genes involved in calcium metabolism: VDR, CASR, CALCR, OPN, MGP, PLAU, AQP1, DGKH, SLC34A1, CLDN14, TRPV6, KLOTHO, ORAI1, ALPL, and RGS14. High-throughput target sequencing was utilized to study the loci of interest. Odds ratios and 95% confidence intervals were used to estimate the association between each SNP and risk of urolithiasis development. Multifactor dimensionality reduction analysis was also carried out to analyze the gene-gene interaction. We found statistically significant (unadjusted p-value < 0.05) associations between calcium urolithiasis and the polymorphisms in the following genes: CASR rs1042636 (OR = 3.18 for allele A), CALCR rs1801197 (OR = 6.84 for allele A), and ORAI1 rs6486795 (OR = 2.25 for allele C). The maximum OR was shown for AA genotypes in loci rs1042636 (CASR) and rs1801197 (CALCR) (OR = 4.71, OR = 11.8, respectively). After adjustment by Benjamini-Hochberg FDR we found only CALCR (rs1801197) was significantly associated with the risk of calcium urolithiasis development. There was no relationship between recurrent course of the disease and family history of urolithiasis in investigated patients. Thus we found a statistically significant association of polymorphism rs1801197 (gene CALCR) with calcium urolithiasis in Russian population.}, }
@article {pmid33914065, year = {2022}, author = {Harmacek, D and Blanchard, A and Wuerzner, G and Maillard, M and Jeunemaitre, X and Azizi, M and Bonny, O}, title = {Acute decrease of urine calcium by amiloride in healthy volunteers under high-sodium diet.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {37}, number = {2}, pages = {298-303}, doi = {10.1093/ndt/gfab159}, pmid = {33914065}, issn = {1460-2385}, mesh = {*Amiloride/pharmacology ; Animals ; *Calcium ; Diuretics/pharmacology ; Healthy Volunteers ; Humans ; Male ; Potassium/metabolism ; Sodium/metabolism ; }, abstract = {BACKGROUND: Amiloride is a competitive blocker of the epithelial sodium (Na) channel in the renal collecting duct. It is a less potent diuretic than thiazides or loop diuretics, but is often used in association with its potassium (K)-sparing profile. Whether amiloride has a hypocalciuric effect similar to thiazides remains unclear. Animal studies and experiments on cell lines suggested that amiloride increases calcium (Ca) reabsorption in the distal nephron, but human studies are scarce.<br><br>METHODS: We performed a post hoc analysis of a study with 48 healthy males (mean &#xb1; standard deviation age, 23.2&#x2009;&#xb1;&#x2009;3.9&#x2009;years) who were assigned to a high-Na/low-K diet for 7&#x2009;days before receiving 20&#x2009;mg of amiloride orally. Urinary excretions of electrolytes were measured at 3 and 6&#x2009;h afterwards; we calculated the relative changes in urinary excretion rates after amiloride administration.<br><br>RESULTS: The high-Na/low-K diet led to an expected suppression of plasma renin and aldosterone. Amiloride showed a mild natriuretic effect associated with a decreased kaliuresis. Urinary Ca excretion dropped substantially (by 80%) 3&#x2009;h after amiloride administration and remained low at the sixth hour. At the same time, fractional excretion of lithium decreased by a third, reflecting an increased proximal tubular reabsorption.<br><br>CONCLUSIONS: During a high-Na/low-K diet, amiloride had a strong acute hypocalciuric effect, most probably mediated by increased proximal Ca reabsorption, even though a distal effect cannot be excluded. Further studies should establish if chronic amiloride or combined amiloride/thiazide treatment may decrease calciuria more efficiently and be useful in preventing kidney stones.}, }
@article {pmid33901996, year = {2020}, author = {Gomes Coutinho, AG and Pinheiro, E and Fernandez, R}, title = {The calcium sensing receptor modulates H[+]-ATPase activity in intercalated cells.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {71}, number = {6}, pages = {}, doi = {10.26402/jpp.2020.6.09}, pmid = {33901996}, issn = {1899-1505}, mesh = {Animals ; Calcium/*metabolism ; Dogs ; Epithelial Cells/*metabolism ; Gadolinium/pharmacology ; Hydrogen-Ion Concentration ; Madin Darby Canine Kidney Cells ; Neomycin/pharmacology ; Phenethylamines/pharmacology ; Propylamines/pharmacology ; Proton-Translocating ATPases/*metabolism ; Receptors, Calcium-Sensing/agonists/*metabolism ; Thapsigargin/pharmacology ; Type C Phospholipases/metabolism ; }, abstract = {Previous studies found that calcium sensing receptor (CaSR) it's expressed in intercalated cells of the collecting duct and that its activation by calcium in the luminal membrane promotes acidification of urine. Therefore, the aim of the study was to analyze the effects of CaSR stimulus on the biochemical activity of the vacuolar H[+]-ATPase in a cellular model of intercalated cells, MDCK-C11 cells. Biochemical activity of H[+]-ATPase was performed using cell homogenates and the inorganic phosphate released was determined by a colorimetric method. Changes in cytosolic ionized calcium ([Ca[2+]]i) were also determined using Fluo-4. A significant increase of vacuolar H[+]-ATPase activity was observed when the CaSR was stimulated with agonists such as Gd[3+] (300 μM), neomycin (200 μM) and by the calcimimetic R-568 (1 μM). This activity was also stimulated in a dose-dependent fashion by changes in extracellular Ca[2+] concentration ([Ca[2+]]o) between 10[-2] and 2 mM. The calciolytic NPS 2143 (150 nM) significantly reduced the vacuolar H[+]-ATPase activity observed with 2 mM [Ca[2+]]o. Inhibition of phospholipase C (PLC) activity with U73122 (5 x 10[-7] M) reversed the increase in pump activity observed in the presence of Gd[3+]. Activation of CaSR by the specific CaSR agonist R-568 produced a sustained rise of [Ca[2+]]i, an effect that disappears when extracellular calcium was removed in the presence of thapsigargin. In summary, CaSR stimulation induces an increase in the vacuolar H[+]-ATPase activity of MDCK-C11 cells, an effect that involves an increase in [Ca[2+]]i and require PLC activity. The consequent decrease in intratubular pH could lead to increase ionization of luminal calcium, potentially reducing the formation of calcium phosphate stones.}, }
@article {pmid33818937, year = {2021}, author = {Porhanov, VA and Medvedev, VL and Budanov, AA and Kurzanov, AN and Basov, AA}, title = {[Determination of calcium metabolism markers concentration in patients with calcium oxalate nephrolithiasis].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {1}, pages = {60-65}, pmid = {33818937}, issn = {1728-2985}, mesh = {Calcium ; Calcium Oxalate ; Humans ; *Kidney Calculi ; *Nephrolithiasis ; Osteopontin ; *Urolithiasis ; }, abstract = {UNLABELLED: THE AIM OF THE RESEARCH: to reveal the relationship of various markers of calcium metabolism (osteopontin (OPN), parathyroid hormone-related protein (PTHrP), vitamin D, parathyroid hormone (PTH)) on the course of urolithiasis (Urolithiasis) in patients with calcium oxalate nephrolithiasis.<br><br>MATERIALS AND METHODS: 100 people were examined, the following groups were included: group 1 - patients with calcium oxalate primary nephrolithiasis (n=41), group 2 - with calcium oxalate recurrent nephrolithiasis (n=39). Group 3 included conditionally healthy volunteers (n=20). The studies were carried out by the immunoenzymometric ELIZA and biochemical methods using appropriate test systems.<br><br>RESULTS: in patients with recurrent nephrolithiasis, the serum PTHrP level is 54.6 (25.4-78.2) pg / ml, which is 3.7 times higher than in conventionally healthy individuals; the level of osteopontin is more than 1.5 times higher and amounts to 1.820 (0.991-2.212) pg / ml. In the group of primary nephrolithiasis, the level of PTHrP is 2-2.5 times higher than in conventionally healthy people. In patients with primary nephrolithiasis, the blood calcium level does not correlate with the level of PTHrP in the blood (r=- 0.0173, p> 0.05), as in the group with recurrent nephrolithiasis (r=0.0223, p>0.05).<br><br>DISCUSSION: in patients with recurrent nephrolithiasis in the preoperative period, the serum levels of osteopontin and PTHrP in the blood serum were higher than in patients who were first diagnosed with urolithiasis, the data obtained can be used as a criterion for predicting the risk of recurrence of urolithiasis in the postoperative period. The blood calcium level does not have a statistically significant relationship with PTHrP, which allows us to assume that PTHrP has other mechanisms of influence on the development of urolithiasis, given the data obtained that the PTHrP level in patients with primary and recurrent nephrolithiasis is higher than in conditionally healthy people.<br><br>CONCLUSION: Determination of the level of PTHrP and osteopontin in patients with urolithiasis allows predicting the risk of recurrence of urolithiasis at the stage of primary calcium oxalate nephrolithiasis. Determination of the level of PTHrP makes it possible to predict the risks of developing urolithiasis in conventionally healthy individuals, which can be used for targeted prevention of an unfavorable course of urolithiasis by prescribing timely adequate rational therapy and correcting the patients diet. At the same time, no correlation was found between the level of PTHrP and the level of blood calcium in patients with calcium oxalate nephrolithiasis; therefore, further studies of the role of this protein in the pathogenesis of urolithiasis are needed.}, }
@article {pmid33808324, year = {2021}, author = {Liu, CJ and Cheng, CW and Tsai, YS and Huang, HS}, title = {Crosstalk between Renal and Vascular Calcium Signaling: The Link between Nephrolithiasis and Vascular Calcification.}, journal = {International journal of molecular sciences}, volume = {22}, number = {7}, pages = {}, pmid = {33808324}, issn = {1422-0067}, mesh = {Animals ; Calcium/metabolism ; Calcium Signaling/*physiology ; Endothelial Cells/metabolism ; Humans ; Hypercalciuria/genetics/metabolism/physiopathology ; Kidney/metabolism ; Kidney Calculi/metabolism ; Myocytes, Smooth Muscle/metabolism ; Nephrolithiasis/*metabolism/physiopathology ; Receptors, Calcium-Sensing/genetics ; Vascular Calcification/genetics/*metabolism/physiopathology ; }, abstract = {Calcium (Ca[2+]) is an important mediator of multicellular homeostasis and is involved in several diseases. The interplay among the kidney, bone, intestine, and parathyroid gland in Ca[2+] homeostasis is strictly modulated by numerous hormones and signaling pathways. The calcium-sensing receptor (CaSR) is a G protein-coupled receptor, that is expressed in calcitropic tissues such as the parathyroid gland and the kidney, plays a pivotal role in Ca[2+] regulation. CaSR is important for renal Ca[2+], as a mutation in this receptor leads to hypercalciuria and calcium nephrolithiasis. In addition, CaSR is also widely expressed in the vascular system, including vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) and participates in the process of vascular calcification. Aberrant Ca[2+] sensing by the kidney and VSMCs, owing to altered CaSR expression or function, is associated with the formation of nephrolithiasis and vascular calcification. Based on emerging epidemiological evidence, patients with nephrolithiasis have a higher risk of vascular calcification, but the exact mechanism linking the two conditions is unclear. However, a dysregulation in Ca[2+] homeostasis and dysfunction in CaSR might be the connection between the two. This review summarizes renal calcium handling and calcium signaling in the vascular system, with a special focus on the link between nephrolithiasis and vascular calcification.}, }
@article {pmid33802660, year = {2021}, author = {Awuah Boadi, E and Shin, S and Yeroushalmi, S and Choi, BE and Li, P and Bandyopadhyay, BC}, title = {Modulation of Tubular pH by Acetazolamide in a Ca[2+] Transport Deficient Mice Facilitates Calcium Nephrolithiasis.}, journal = {International journal of molecular sciences}, volume = {22}, number = {6}, pages = {}, pmid = {33802660}, issn = {1422-0067}, support = {DK102043/DK/NIDDK NIH HHS/United States ; R01 DK102043/DK/NIDDK NIH HHS/United States ; R21 EB021483/EB/NIBIB NIH HHS/United States ; }, mesh = {Acetazolamide/*pharmacology ; Animals ; Biological Transport/drug effects ; Calcinosis/complications ; Calcium/*metabolism ; Endoplasmic Reticulum Stress/drug effects ; Fibrosis ; Hydrogen-Ion Concentration ; Inflammation/pathology ; Kidney Tubules, Proximal/drug effects/*metabolism/*pathology ; Mice ; Nephrolithiasis/*metabolism/*pathology/urine ; Oxidative Stress/drug effects ; TRPC Cation Channels/metabolism ; Up-Regulation/drug effects ; }, abstract = {Proximal tubular (PT) acidosis, which alkalinizes the urinary filtrate, together with Ca[2+] supersaturation in PT can induce luminal calcium phosphate (CaP) crystal formation. While such CaP crystals are known to act as a nidus for CaP/calcium oxalate (CaOx) mixed stone formation, the regulation of PT luminal Ca[2+] concentration ([Ca[2+]]) under elevated pH and/or high [Ca[2+]] conditions are unknown. Since we found that transient receptor potential canonical 3 (TRPC3) knockout (KO; -/-) mice could produce mild hypercalciuria with CaP urine crystals, we alkalinized the tubular pH in TRPC3-/- mice by oral acetazolamide (0.08%) to develop mixed urinary crystals akin to clinical signs of calcium nephrolithiasis (CaNL). Our ratiometric (λ340/380) intracellular [Ca[2+]] measurements reveal that such alkalization not only upsurges Ca[2+] influx into PT cells, but the mode of Ca[2+] entry switches from receptor-operated to store-operated pathway. Electrophysiological experiments show enhanced bicarbonate related current activity in treated PT cells which may determine the stone-forming phenotypes (CaP or CaP/CaOx). Moreover, such alkalization promotes reactive oxygen species generation, and upregulation of calcification, inflammation, fibrosis, and apoptosis in PT cells, which were exacerbated in absence of TRPC3. Altogether, the pH-induced alteration of the Ca[2+] signaling signature in PT cells from TRPC3 ablated mice exacerbated the pathophysiology of mixed urinary stone formation, which may aid in uncovering the downstream mechanism of CaNL.}, }
@article {pmid33796889, year = {2022}, author = {Downie, ML and Alexander, RT}, title = {Molecular mechanisms altering tubular calcium reabsorption.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {37}, number = {4}, pages = {707-718}, pmid = {33796889}, issn = {1432-198X}, support = {//CIHR/Canada ; }, mesh = {*Calcium/metabolism ; Calcium, Dietary ; Claudins/genetics/metabolism ; Female ; Humans ; Hypercalciuria/genetics/metabolism ; *Kidney Calculi ; Male ; }, abstract = {The majority of calcium filtered by the glomerulus is reabsorbed along the nephron. Most is reabsorbed from the proximal tubule (> 60%) via a paracellular pathway composed of the tight junction proteins claudins-2 and -12, a process driven by sodium and consequently water reabsorption. The thick ascending limb reabsorbs the next greatest amount of calcium (20-25%), also by a paracellular pathway composed of claudins-16 and -19. This pathway is regulated by the CaSR, whose activity increases the expression of claudin-14, a protein that blocks paracellular calcium reabsorption. The fine tuning of urinary calcium excretion occurs in the distal convoluted and connecting tubule by a transcellular pathway composed of the apical calcium channel TRPV5, the calcium shuttling protein calbindin-D28K and the basolateral proteins PMCA1b and the sodium calcium exchanger, NCX. Not surprisingly, mutations in a subset of these genes cause monogenic disorders with hypercalciuria as a part of the phenotype. More commonly, "idiopathic" hypercalciuria is encountered clinically with genetic variations in CLDN14, the CASR and TRPV5 associating with kidney stones and increased urinary calcium excretion. An understanding of the molecular pathways conferring kidney tubular calcium reabsorption is employed in this review to help explain how dietary and medical interventions for this disorder lower urinary calcium excretion.}, }
@article {pmid33744642, year = {2021}, author = {de Carvalho, JF and Churilov, LP}, title = {Safety of megadose of vitamin D in patients with nephrolithiasis.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {87-88}, number = {}, pages = {111201}, doi = {10.1016/j.nut.2021.111201}, pmid = {33744642}, issn = {1873-1244}, mesh = {Aged ; Calcium ; Humans ; *Kidney Calculi ; Male ; Middle Aged ; Parathyroid Hormone ; Vitamin D ; *Vitamin D Deficiency/complications/drug therapy ; Vitamins ; }, abstract = {OBJECTIVE: This article describes two patients with renal lithiasis who received a megadose of 25-hydroxy vitamin D (25[OH]D) and had a good outcome.<br><br>METHODS: The first case reports a 74-year-old man with a long-term history of renal lithiasis and about four episodes of renal crisis. He was treated once with extracorporeal shock wave lithotripsy. He also had a history of dyslipidemia, myocardial infarction, and stroke. Laboratory tests demonstrated 25(OH)D of 28 ng/mL (normal range (nr): >30 ng/mL), normal lipid levels, creatinine of 1.1 mg/dL, and homocysteine of 26.6 mcmol/L (nr: 5-15 mcmol/L); parathyroid hormone (PTH) was high at 67.3 pg/mL (nr: 10-65 pg/mL), serum total calcium was 8.6 mg/dL, 24-h urinary calcium was 139 mg/d (normal range 100-300 mg/d), and urinary sediment was normal. He received 50 000 IU per week of vitamin D for 3 mo, and 25(OH)D increased to 36.6 ng/mL. Urinary calcium was 142 mg/d, PTH was 46.7 pg/mL, and serum calcium was 9.6 mg/dL. No renal crisis was perceived. He asked for an alternative form of medication since he usually would forget to take drugs. Vitamin D in a single dose of 600 000 IU intramuscular was prescribed. He was asked to increase water intake to 2 to 3 L/d. After 3 mo his 25(OH)D was 75.0 ng/mL, serum calcium was 9.2 mg/dL, urinary calcium was 148 mg/d, and PTH was 38.7 pg/mL. He had no episodes of lithiasis renal crisis. Folic acid and methylcobalamin were added, and homocysteine normalized. At follow-up 3 y later, the patient was asymptomatic, cardiologic evaluation was stable without any other renal lithiasis crises, 25(OH)D continued to be normal at 62 ng/mL, and he received a megadose of vitamin D every 6 mo. Renal ultrasound revealed only microlithiasis. The second case reports a 52-year-old man with a long-term history of renal lithiasis experienced since he was 30 y old, with three renal crisis episodes. He was treated with an extracorporeal shock wave three times. Laboratory tests demonstrated 25(OH)D 18 ng/mL, normal biochemistry, total serum calcium of 10.2 mg/dL, 24-h urinary calcium of 154 mg/d, and normal urinary sediment. He received 50 000 IU per week of 25(OH)D for 3 mo, and 25(OH)D increased to 40.3 ng/mL. Urinary calcium was 167 mg/d, PTH was 35.3 pg/mL, and serum calcium was 10.1 mg/dL. No renal crisis was perceived. He asked for an alternative form of medication, and vitamin D in a single dose of 600 000 IU intramuscular was prescribed. He was asked to increase water intake to 2 to 3 L/d. After 3 mo, his 25(OH)D was 82.0 ng/mL, serum calcium was 9.6 mg/dL, urinary calcium was 175 mg/d, and PTH was 35.3 pg/mL. The renal ultrasound was unchanged. He had no episodes of lithiasis renal crisis. At follow-up 4 y later, the patient was asymptomatic without any other renal lithiasis crises, a renal ultrasound revealed a reduction of calculi size to microlithiasis, 25(OH)D continues normal, and he received a megadose of this vitamin every 4 mo.<br><br>CONCLUSION: To the best of our knowledge, this is the first description of a megadose of vitamin D used in patients with nephrolithiasis. Furthermore, this shows the safety of this strategy in patients without hypercalciuria.}, }
@article {pmid33573587, year = {2022}, author = {Kumar, A and Balbach, J}, title = {Inactivation of Parathyroid Hormone: Perspectives of Drug Discovery to Combating Hyperparathyroidism.}, journal = {Current molecular pharmacology}, volume = {15}, number = {2}, pages = {292-305}, doi = {10.2174/1874467214666210126112839}, pmid = {33573587}, issn = {1874-4702}, mesh = {Calcium/metabolism ; Drug Discovery ; Humans ; *Hyperparathyroidism/drug therapy/metabolism ; Kidney/metabolism ; *Parathyroid Hormone/metabolism ; }, abstract = {Hormonal coordination is tightly regulated within the human body and thus regulates human physiology. The parathyroid hormone (PTH), a member of the endocrine system, regulates the calcium and phosphate level within the human body. Under non-physiological conditions, PTH levels get upregulated (hyperparathyroidism) or downregulated (hypoparathyroidism) due to external or internal factors. In case of hyperparathyroidism, elevated PTH stimulates cellular receptors present in the bones, kidneys, and intestines to increase the blood calcium level, leading to calcium deposition. This eventually causes various symptoms, including kidney stones. Currently, there is no known medication that directly targets PTH in order to suppress its function. Therefore, it is of great interest to find novel small molecules or any other means that can modulate PTH function. The molecular signaling of PTH starts by binding its N-terminus to the G-protein coupled PTH1/2 receptor. Therefore, any intervention that affects the N-terminus of PTH could be a lead candidate for treating hyperparathyroidism. As a proof-of-concept, there are various possibilities to inhibit molecular PTH function by (i) a small molecule, (ii) N-terminal PTH phosphorylation, (iii) fibril formation and (iv) residue-specific mutations. These modifications put PTH into an inactive state, which will be discussed in detail in this review article. We anticipate that exploring small molecules or other means that affect the N-terminus of PTH could be lead candidates in combating hyperparathyroidism.}, }
@article {pmid33483520, year = {2021}, author = {Yi, F and Garrett, T and Deisseroth, K and Haario, H and Stone, E and Lawrence, JJ}, title = {Septohippocampal transmission from parvalbumin-positive neurons features rapid recovery from synaptic depression.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {2117}, pmid = {33483520}, issn = {2045-2322}, support = {R01 NS069689/NH/NIH HHS/United States ; R01 NS069689-04S1/NH/NIH HHS/United States ; P20RR015583/RR/NCRR NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Calcium/metabolism ; Hippocampus/cytology/*physiology ; Membrane Potentials/physiology ; Mice, Transgenic ; Models, Neurological ; Neurons/cytology/metabolism/*physiology ; Optogenetics/methods ; Parvalbumins/*metabolism ; Patch-Clamp Techniques ; Septum of Brain/cytology/*physiology ; Synapses/*physiology ; Synaptic Transmission/*physiology ; }, abstract = {Parvalbumin-containing projection neurons of the medial-septum-diagonal band of Broca ([Formula: see text]) are essential for hippocampal rhythms and learning operations yet are poorly understood at cellular and synaptic levels. We combined electrophysiological, optogenetic, and modeling approaches to investigate [Formula: see text] neuronal properties. [Formula: see text] neurons had intrinsic membrane properties distinct from acetylcholine- and somatostatin-containing MS-DBB subtypes. Viral expression of the fast-kinetic channelrhodopsin ChETA-YFP elicited action potentials to brief (1-2 ms) 470 nm light pulses. To investigate [Formula: see text] transmission, light pulses at 5-50 Hz frequencies generated trains of inhibitory postsynaptic currents (IPSCs) in CA1 stratum oriens interneurons. Using a similar approach, optogenetic activation of local hippocampal PV ([Formula: see text]) neurons generated trains of [Formula: see text]-mediated IPSCs in CA1 pyramidal neurons. Both synapse types exhibited short-term depression (STD) of IPSCs. However, relative to [Formula: see text] synapses, [Formula: see text] synapses possessed lower initial release probability, transiently resisted STD at gamma (20-50 Hz) frequencies, and recovered more rapidly from synaptic depression. Experimentally-constrained mathematical synapse models explored mechanistic differences. Relative to the [Formula: see text] model, the [Formula: see text] model exhibited higher sensitivity to calcium accumulation, permitting a faster rate of calcium-dependent recovery from STD. In conclusion, resistance of [Formula: see text] synapses to STD during short gamma bursts enables robust long-range GABAergic transmission from MS-DBB to hippocampus.}, }
@article {pmid33420577, year = {2021}, author = {Charles, PY and Letavernier, E and Périé, S and Gauthé, M and Daudon, M and Haymann, JP}, title = {Effect of parathyroidectomy on renal stone recurrence.}, journal = {Urolithiasis}, volume = {49}, number = {4}, pages = {327-334}, pmid = {33420577}, issn = {2194-7236}, mesh = {Adult ; Female ; Humans ; Hyperparathyroidism, Primary/*complications/*surgery ; Kidney Calculi/*complications ; Male ; Middle Aged ; *Parathyroidectomy ; Recurrence ; }, abstract = {Parathyroidectomy (PTX) is routinely performed in hypercalciuric renal stone patients with primary hyperparathyroidism (PHPT). However, some data indicate a persistent stone activity following PTX, raising the issue of the link between PHPT and stone disease. We performed an observational study on 30 renal stone patients diagnosed with PHPT. Patients were selected among 1448 hypercalciuric patients referred in our department for a diagnostic evaluation. Patients with no parathyroid surgery or any biological follow-up were excluded. Clinical and biological data (including 24-h urine collection and a calcium load test) were collected before and within 12 months following surgery. Stone recurrence was evaluated by direct phone contact (median 43 months). Comparison of biological data before and after surgery showed a significant decrease of ionized calcium and serum parathyroid hormone after PTX. All stones contained calcium-dependent species such as carbapatite, brushite or dihydrate calcium oxalate. Urine saturation indexes and calciuria significantly decreased after surgery (from 9.9 to 5.9 mmol/d, p < 0.0001), but a persistent hypercalciuria was detected in 47% of patients. The other stone risk factors including diuresis stayed similar. Stone activity that was increasing (from 0.20-0.30 to 0.50-0.75/year) the 2 years before PTX, significantly decreased after surgery [0.05-0.15/year (p < 0.001)]. PTX in calcium-dependent renal stone formers with PHPT significantly decreases both stone recurrence and urine saturation indexes. However, PTX unmasked an underlying renal stone disease related to idiopathic hypercalciuria in half of patients with a remaining stone activity, testifying the need for patient's follow-up to prevent stone recurrence.}, }
@article {pmid33419710, year = {2021}, author = {Keller, EX and De Coninck, V and Pietropaolo, A and Somani, B and Haymann, JP and Daudon, M}, title = {Metabolic Evaluation: Place of the Calcium Load Test: How, When, For Whom, and Why?.}, journal = {European urology focus}, volume = {7}, number = {1}, pages = {26-30}, doi = {10.1016/j.euf.2020.12.019}, pmid = {33419710}, issn = {2405-4569}, mesh = {Calcium/*metabolism ; Humans ; Hypercalciuria/*diagnosis ; Hyperparathyroidism/diagnosis ; Kidney Calculi/diagnosis/*etiology ; *Urinary Calculi ; }, abstract = {Most human urinary stones are calcium-based and are often associated with hypercalciuria. A simple test described in 1975 by Pak et al allows for pathogenic classification of hypercalciuria: the calcium load test (CLT). The CLT explores calcium homeostasis after a low-calcium diet and then a calcium load (typically oral administration of 1 g of elemental calcium). Only simple laboratory equipment is required. Inadequate calcium excretion after a calcium-free diet or a calcium load is suggestive of resorptive or absorptive hypercalciuria, respectively. The CLT is particularly valuable in diagnosing primary hyperparathyroidism, even in most early stages of this disease. PATIENT SUMMARY: Kidney stone formation can be linked to calcium metabolism. When high calcium levels are found in urine despite adequate diet changes, a calcium load test may help to understand the underlying mechanisms. Urine and blood levels are explored during a low-calcium diet phase, and after a calcium load phase in the test. The calcium load test is particularly advantageous for revealing abnormally high function of the parathyroid gland, which is called hyperparathyroidism.}, }
@article {pmid33377691, year = {2020}, author = {Litvinova, MM and Filippova, TV and Khafizov, KF and Svetlichnaya, DV and Ahmedzyanova, DA and Rudenko, VI and Gadzhieva, ZK and Shumikhina, MV}, title = {[A complicated case of calcium urolithiasis in a carrier of SLC7A9 gene mutation responsible for cystinuria].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {6}, pages = {126-130}, pmid = {33377691}, issn = {1728-2985}, mesh = {Amino Acid Transport Systems, Basic/genetics ; Calcium ; Child ; *Cystinuria/genetics ; Humans ; Mutation ; *Urinary Calculi ; *Urolithiasis/genetics ; }, abstract = {The article describes a clinical case of kidney stone disease (KSD) in a child of 4 y.o. with calcium urolithiasis. Analysis of chemical content of the kidney stones revealed their calcium-oxalate composition. According to the results of clinical exome sequencing the patient found to be a heterozygous carrier of a pathogenic variant c.695A>G (p.Tyr232Cys) in the gene SLC7A9, attributable for an autosomal recessive form of cystinuria type B. Because of the uroliths calcium composition the patient was also genotyped for SNPs in 15 genes involved in calcium metabolism. Polymorphisms associated with increased risk of calcium urolithiasis were found in 8 of 15 tested genes. The findings could explain clinical features of the patient.}, }
@article {pmid33174123, year = {2021}, author = {Lanka, P and Devana, SK and Singh, SK and Sapehia, D and Kaur, J}, title = {Klotho gene polymorphism in renal stone formers from Northwestern India.}, journal = {Urolithiasis}, volume = {49}, number = {3}, pages = {195-199}, pmid = {33174123}, issn = {2194-7236}, mesh = {Adolescent ; Adult ; Calcium/metabolism ; Case-Control Studies ; Female ; *Genetic Predisposition to Disease ; Genotyping Techniques ; Glucuronidase/*genetics/metabolism ; Humans ; India/epidemiology ; Kidney Calculi/epidemiology/*genetics/metabolism ; Klotho Proteins ; Male ; Middle Aged ; Phosphorus/metabolism ; Polymorphism, Single Nucleotide ; Prospective Studies ; White People/genetics ; Young Adult ; }, abstract = {Klotho gene is an important gene involved in calcium homeostasis, and polymorphisms of this gene may render the individual prone to renal stone formation. We evaluated G395A single nucleotide polymorphisms (SNPs) of Klotho gene at rs1207568 in renal stone patients of North India. This was a prospective study involving 150 patients of renal stone disease (aged 15-60 years) and 100 age- and sex-matched controls. The DNA was isolated and subjected to polymerase chain reaction (PCR) for identifying the G395A Klotho SNPs at rs1207568. Confronting two pair primers were used, and gel electrophoresis showing two bands at 175,252 bp was considered as GG genotype, three bands at 121,175 and 252 bp as GA and two bands at 121 and 252 bp as AA genotype. The association between genotype and cases was evaluated by using Chi-square test and logistic regression analysis. Cases and controls were well matched for age (40.65 vs 42.06, p = 0.063) and sex (p = 0.420). Significantly high proportion of patients with renal stones had GG genotype as compared to controls (odds ratio (OR) 2.37(1.39,4.03), p = 0.001). None of the participants (cases and controls) had homozygous recessive AA genotype. The risk of stone formation was significantly higher in the population carrying G allele {OR 1.94 (1.225-3.073), p 0.004}. Mean serum calcium was higher in stone formers with GG genotype as compared to those with GA genotype (9.16 mg/dl vs 8.91 mg/dl; p = 0.06). GG genotype of G396A Klotho gene SNPs is associated with renal stone formation. The G allele carrier is twice at risk of renal stone formation. The absence of AA genotype in north-western Indian population remains a curiosity.}, }
@article {pmid33161469, year = {2021}, author = {Stern, JM and Burk, RD and Asplin, J and Krieger, NS and Suadicani, SO and Wang, Y and Usyk, M and Lee, JA and Chen, L and Becker, J and Chan, M and Bushinsky, DA}, title = {Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats.}, journal = {Urolithiasis}, volume = {49}, number = {3}, pages = {185-193}, pmid = {33161469}, issn = {2194-7236}, mesh = {Administration, Oral ; Animals ; Anti-Bacterial Agents/administration &amp; dosage/*adverse effects ; Calcium/metabolism/urine ; Ciprofloxacin/administration &amp; dosage/adverse effects ; Disease Models, Animal ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Hypercalciuria/*complications/genetics/microbiology/urine ; Kidney Calculi/diagnosis/*etiology/urine ; RNA, Ribosomal, 16S/genetics ; Rats ; Renal Elimination ; Trimethoprim, Sulfamethoxazole Drug Combination/administration &amp; dosage/adverse effects ; }, abstract = {Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = - 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.}, }
@article {pmid33042926, year = {2020}, author = {Aoun, B and Sanjad, S and Degheili, JA and Barhoumi, A and Bassyouni, A and Karam, PE}, title = {Kidney and Metabolic Phenotypes in Glycogen Storage Disease Type-I Patients.}, journal = {Frontiers in pediatrics}, volume = {8}, number = {}, pages = {591}, pmid = {33042926}, issn = {2296-2360}, abstract = {Patients and Methods: A retrospective chart review of 32 GSD- I patients, followed at the American University of Beirut Medical Center, between 2007 and 2018 was conducted. Diagnosis was confirmed by enzymatic and/or genetic studies. Clinical presentation, growth, and kidney outcome were assessed. All patients were evaluated for body mass index, blood parameters of metabolic control including uric acid, alanine, lactic acid, and triglycerides in blood. Kidney evaluation included creatinine clearance, microalbuminuria, citraturia, and calciuria as well as urine microalbumin/creatinine ratio. Results: Almost one third of GSD-I patients developed microalbuminuria. This was detected below 7 months of age in 36% of patients who required early treatment with ACEI with significant reduction in albuminuria. Kidney stones were present in 6% and were associated with hypercalciuria and hypocitraturia. Poor metabolic control reflected by hyperuricemia, lactic acidosis, and hyperalaninemia were noted only in patients who developed microalbuminuria. Conclusion: Glomerular injury may appear in early infancy in poorly controlled patients. Adequate metabolic control and ACEI therapy may improve kidney outcome in GSD I patients. Plasma alanine appears to be a promising and reliable marker reflecting metabolic control in GSD-I patients.}, }
@article {pmid35782986, year = {2022}, author = {Guo, S and Chia, W and Wang, H and Bushinsky, DA and Zhong, B and Favus, MJ}, title = {Vitamin D receptor (VDR) contributes to the development of hypercalciuria by sensitizing VDR target genes to vitamin D in a genetic hypercalciuric stone-forming (GHS) rat model.}, journal = {Genes &amp; diseases}, volume = {9}, number = {3}, pages = {797-806}, pmid = {35782986}, issn = {2352-3042}, abstract = {Human idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis with perturbed calcium metabolism with increased bone resorption and decreased renal calcium reabsorption, which can be phenotype-copied in the genetic hypercalciuric stone-forming (GHS) rat model. We previously demonstrated that high VDR expression plays important roles in the development of hypercalciuria in the GHS rats. However, the underlying mechanism through which VDR impact hypercalciuria development remains to be fully understood. Here, we sought to determine how VDR regulated its target genes that are implicated in calcium homeostasis and potentially hypercalciuria. We found that VDR expression in the GHS rats was elevated in the calcium transporting tissues, as well as in the thymus and prostate, but not in lung, brain, heart, liver and spleen, when compared with control SD rats. Snail expression in the GHS rats was significantly downregulated in kidney, intestine, thymus and testis. Intraperitoneal injection of 1,25(OH)2D3 significantly upregulated the expression of renal calcium sensing receptor (CaSR), intestinal calcium transporters transient receptor potential vanilloid type 6 (TRPV6), and VDR in GHS rats, compared with that in control SD rats. ChIP assays revealed that VDR specifically bound to the proximal promoters of target genes, followed by histone H3 hyperacetylation or hypermethylation. Collectively, our results suggest that elevated VDR expression may contribute to the development of hypercalciuria by sensitizing VDR target genes to 1,25(OH)2D3 through histone modifications at their promoter regions in a genetic hypercalciuric stone-forming (GHS) rat model.}, }
@article {pmid32971767, year = {2020}, author = {Schapher, M and Koch, M and Weidner, D and Scholz, M and Wirtz, S and Mahajan, A and Herrmann, I and Singh, J and Knopf, J and Leppkes, M and Schauer, C and Grüneboom, A and Alexiou, C and Schett, G and Iro, H and Muñoz, LE and Herrmann, M}, title = {Neutrophil Extracellular Traps Promote the Development and Growth of Human Salivary Stones.}, journal = {Cells}, volume = {9}, number = {9}, pages = {}, pmid = {32971767}, issn = {2073-4409}, mesh = {Adult ; Biomarkers/metabolism ; Calcium/chemistry/*metabolism ; Cohort Studies ; DNA/genetics/metabolism ; Extracellular Traps/*immunology ; Female ; Gene Expression ; Humans ; Image Processing, Computer-Assisted ; Leukocyte Elastase/genetics/immunology ; Lithotripsy ; Male ; Middle Aged ; Neutrophils/immunology/*pathology ; Salivary Gland Calculi/diagnostic imaging/immunology/*pathology/surgery ; Salivary Glands/diagnostic imaging/immunology/*pathology/surgery ; Sialadenitis/diagnostic imaging/immunology/*pathology/surgery ; Ultrasonography ; X-Ray Microtomography ; }, abstract = {Salivary gland stones, or sialoliths, are the most common cause of the obstruction of salivary glands. The mechanism behind the formation of sialoliths has been elusive. Symptomatic sialolithiasis has a prevalence of 0.45% in the general population, is characterized by recurrent painful periprandial swelling of the affected gland, and often results in sialadenitis with the need for surgical intervention. Here, we show by the use of immunohistochemistry, immunofluorescence, computed tomography (CT) scans and reconstructions, special dye techniques, bacterial genotyping, and enzyme activity analyses that neutrophil extracellular traps (NETs) initiate the formation and growth of sialoliths in humans. The deposition of neutrophil granulocyte extracellular DNA around small crystals results in the dense aggregation of the latter, and the subsequent mineralization creates alternating layers of dense mineral, which are predominantly calcium salt deposits and DNA. The further agglomeration and appositional growth of these structures promotes the development of macroscopic sialoliths that finally occlude the efferent ducts of the salivary glands, causing clinical symptoms and salivary gland dysfunction. These findings provide an entirely novel insight into the mechanism of sialolithogenesis, in which an immune system-mediated response essentially participates in the physicochemical process of concrement formation and growth.}, }
@article {pmid32825353, year = {2020}, author = {Milart, J and Lewicka, A and Jobs, K and Wawrzyniak, A and Majder-Łopatka, M and Kalicki, B}, title = {Effect of Vitamin D Treatment on Dynamics of Stones Formation in the Urinary Tract and Bone Density in Children with Idiopathic Hypercalciuria.}, journal = {Nutrients}, volume = {12}, number = {9}, pages = {}, pmid = {32825353}, issn = {2072-6643}, mesh = {Adolescent ; Bone Density/*drug effects ; Child ; Child Nutritional Physiological Phenomena/*physiology ; Child, Preschool ; *Dietary Supplements ; Female ; Humans ; Hypercalciuria/complications/*metabolism ; Male ; *Negative Results ; Urinary Tract/*metabolism ; Urolithiasis/*etiology ; Vitamin D/administration &amp; dosage/*adverse effects/analogs &amp; derivatives/blood/*pharmacology ; }, abstract = {Vitamin D supplementation in patients with urolithiasis and hypercalciuria is considered to be unsafe. We analyzed the impact of vitamin D supplementation on selected health status parameters in children with idiopathic hypercalciuria. The study included 36 children with urolithiasis resulting from excessive calcium excretion. The level of calcium and 25(OH)D (hydroxylated vitamin D - calcidiol) in serum, urinary calcium excretion and the presence of stones in urinary tract were assessed prospectively. Blood and urine samples were collected at the time when the patient was qualified for the study and every three months up to 24 month of vitamin D intake at a dose of 400 or 800 IU/day. At time zero and at 12, and 24 months of vitamin D supplementation, densitometry was performed. Supplementation with vitamin D caused a statistically significant increase in the concentration of 25(OH)D in serum. There were no significant changes in calcium concentration in serum, excretion of calcium in urine but also in bone density. There was no significant increase in the risk of formation or development of stones in the urinary tract. Supplementation with vitamin D (400-800 IU/day) in children with idiopathic hypercalciuria significantly increases 25(OH)D concentration, does not affect calciuria, but also does not improve bone density.}, }
@article {pmid32777848, year = {2020}, author = {Zhou, Y and Lower, EE}, title = {Balancing Altered Calcium Metabolism with Bone Health in Sarcoidosis.}, journal = {Seminars in respiratory and critical care medicine}, volume = {41}, number = {5}, pages = {618-625}, doi = {10.1055/s-0040-1713009}, pmid = {32777848}, issn = {1098-9048}, mesh = {Age Factors ; Bone Demineralization, Pathologic/etiology/*metabolism/prevention &amp; control ; Calcitriol/blood ; Calcium/*metabolism ; Dietary Supplements/*adverse effects ; Fractures, Bone/prevention &amp; control ; Humans ; Medication Therapy Management ; Pragmatic Clinical Trials as Topic ; Risk Factors ; Sarcoidosis/complications/*metabolism/therapy ; Sex Factors ; Vitamin D/metabolism/*pharmacology ; }, abstract = {Abnormal calcium metabolism in sarcoidosis patients can lead to hypercalcemia, hypercalciuria, and kidney stones. Hypercalcemia in sarcoidosis is usually due to increased activity of 1α-hydroxylase in macrophages of pulmonary granulomata, resulting in low levels of 25-hydroxyvitamin D and high levels of calcitriol. Vitamin D supplementation may be dangerous for some sarcoidosis patients and is recommended only for those with decreased 25-hydroxyvitamin D and reduced or normal calcitriol level. Diagnosis, treatment of osteoporosis, and maintenance of bone health are complex issues for sarcoidosis patients. An approach to diagnosis and treatment of bone fragility is presented.}, }
@article {pmid32707085, year = {2020}, author = {Sinha, D and Steyer, B and Shahi, PK and Mueller, KP and Valiauga, R and Edwards, KL and Bacig, C and Steltzer, SS and Srinivasan, S and Abdeen, A and Cory, E and Periyasamy, V and Siahpirani, AF and Stone, EM and Tucker, BA and Roy, S and Pattnaik, BR and Saha, K and Gamm, DM}, title = {Human iPSC Modeling Reveals Mutation-Specific Responses to Gene Therapy in a Genotypically Diverse Dominant Maculopathy.}, journal = {American journal of human genetics}, volume = {107}, number = {2}, pages = {278-292}, pmid = {32707085}, issn = {1537-6605}, support = {R01 EY024995/EY/NEI NIH HHS/United States ; T32 HG002760/HG/NHGRI NIH HHS/United States ; R35 GM119644/GM/NIGMS NIH HHS/United States ; U54 HD090256/HD/NICHD NIH HHS/United States ; R01 EY024588/EY/NEI NIH HHS/United States ; F30 EY027699/EY/NEI NIH HHS/United States ; T32 GM008349/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Bestrophins/genetics ; Calcium/metabolism ; Cell Line ; Channelopathies/genetics ; Eye Proteins/genetics ; Gene Editing/methods ; Genetic Therapy/methods ; Genotype ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/*physiology ; Macular Degeneration/*genetics ; Mutation/*genetics ; Retinal Pigment Epithelium/physiology ; }, abstract = {Dominantly inherited disorders are not typically considered to be therapeutic candidates for gene augmentation. Here, we utilized induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) to test the potential of gene augmentation to treat Best disease, a dominant macular dystrophy caused by over 200 missense mutations in BEST1. Gene augmentation in iPSC-RPE fully restored BEST1 calcium-activated chloride channel activity and improved rhodopsin degradation in an iPSC-RPE model of recessive bestrophinopathy as well as in two models of dominant Best disease caused by different mutations in regions encoding ion-binding domains. A third dominant Best disease iPSC-RPE model did not respond to gene augmentation, but showed normalization of BEST1 channel activity following CRISPR-Cas9 editing of the mutant allele. We then subjected all three dominant Best disease iPSC-RPE models to gene editing, which produced premature stop codons specifically within the mutant BEST1 alleles. Single-cell profiling demonstrated no adverse perturbation of retinal pigment epithelium (RPE) transcriptional programs in any model, although off-target analysis detected a silent genomic alteration in one model. These results suggest that gene augmentation is a viable first-line approach for some individuals with dominant Best disease and that non-responders are candidates for alternate approaches such as gene editing. However, testing gene editing strategies for on-target efficiency and off-target events using personalized iPSC-RPE model systems is warranted. In summary, personalized iPSC-RPE models can be used to select among a growing list of gene therapy options to maximize safety and efficacy while minimizing time and cost. Similar scenarios likely exist for other genotypically diverse channelopathies, expanding the therapeutic landscape for affected individuals.}, }
@article {pmid32695257, year = {2020}, author = {Yifan, Z and Benxiang, N and Zheng, X and Luwei, X and Liuhua, Z and Yuzheng, G and Ruipeng, J}, title = {Ceftriaxone Calcium Crystals Induce Acute Kidney Injury by NLRP3-Mediated Inflammation and Oxidative Stress Injury.}, journal = {Oxidative medicine and cellular longevity}, volume = {2020}, number = {}, pages = {6428498}, pmid = {32695257}, issn = {1942-0994}, mesh = {Acute Kidney Injury ; Animals ; Calcium/metabolism ; Ceftriaxone/administration &amp; dosage/*adverse effects ; Cell Line ; Creatinine/blood ; Humans ; Inflammasomes/*metabolism ; Kidney Tubules, Proximal/*metabolism/pathology ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Urolithiasis/etiology/*metabolism ; }, abstract = {OBJECTIVE: To investigate the role of inflammatory reactions and oxidative stress injury in the mechanisms of ceftriaxone calcium crystal-induced acute kidney injury (AKI) both in vivo and in vitro.<br><br>METHODS: Male Sprague Dawley rats were randomly divided into five groups of ten each according to different concentrations of ceftriaxone and calcium. Based on the levels of serum creatinine (Scr) and blood urea nitrogen (BUN), the AKI group was chosen for the subsequent experiments. Kidney histological examination and immunohistochemistry were performed. The expression of NLRP3 and IL-1&#x3b2; protein and the concentrations of oxidative stress markers such as ROS, MDA, and H2O2 in kidney tissues were estimated. In parallel, HK-2 human renal proximal tubule cells were exposed to ceftriaxone calcium crystals. The mRNA expression levels of NLRP3 and IL-1&#x3b2; and the concentrations of oxidative stress markers were evaluated. Finally, cell viability and rat survival were also assessed.<br><br>RESULTS: The results showed that significantly increased Scr and BUN levels, consistent with morphological changes and kidney stones, were found in the rats that received the highest concentration of ceftriaxone (1000&#x2009;mg/kg) combined with calcium (800&#x2009;mg/kg). The activation of the NLRP3 inflammasome axis and the marked elevation of MDA, H2O2, and ROS levels were observed both in vivo and in vitro. High expression of Nrf2, HO-1, and NQO1 was also documented. In addition, cell apoptosis and rat mortality were promoted by ceftriaxone calcium crystals.<br><br>CONCLUSIONS: Notably, we found that ceftriaxone-induced urolithiasis was associated with a high risk of AKI and NLRP3-mediated inflammasome and oxidative stress injury were of major importance in the pathogenesis.}, }
@article {pmid32386861, year = {2020}, author = {Irzyniec, T and Boryń, M and Kasztalska, J and Nowak-Kapusta, Z and Maciejewska-Paszek, I and Grochowska-Niedworok, E}, title = {The effect of an oral sodium phosphate load on parathyroid hormone and fibroblast growth factor 23 secretion in normo- and hypercalciuric stone-forming patients.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {39}, number = {12}, pages = {3804-3812}, doi = {10.1016/j.clnu.2020.04.020}, pmid = {32386861}, issn = {1532-1983}, mesh = {Administration, Oral ; Adult ; Calcium/blood/urine ; Case-Control Studies ; Creatinine/blood ; Female ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors/*blood ; Homeostasis/drug effects ; Humans ; Hypercalciuria/blood/*drug therapy/urine ; Kidney Calculi/blood/*drug therapy/urine ; Male ; Middle Aged ; Parathyroid Hormone/*blood ; Phosphates/*administration &amp; dosage/blood/urine ; Treatment Outcome ; Vitamin D/analogs &amp; derivatives/blood ; }, abstract = {BACKGROUND &amp; AIMS: Abnormalities of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) secretion may cause calcium-phosphate (Ca-P) metabolism disorders in nephrolithiasis. Post-phosphate-load alterations in serum Ca, P and PTH, phosphaturia and calciuria enable monitoring hormonal regulation of Ca-P homeostasis. Our study aimed to determine differences in: 1.selected Ca-P metabolism parameters between healthy and kidney-stone-forming individuals, 2.PTH and FGF23 secretion induced by sodium-phosphate-load(NaP-load) in patients with/without hypercalciuria, 3.secretion of Ca-P related hormones in patients with low and normal/high serum concentrations of 25-hydroxyvitamin D3 (25OHD3).<br><br>METHODS: Sodium phosphates NaH2PO4/Na2HPO4-100mmol were administered orally for five days in 19 hypercalciuric [urinary Ca(U-Ca) 6.5&#xa0;&#xb1;&#xa0;1.7&#xa0;mmol/d]-HSF, 35 normocalciuric (2.5&#xb1;1&#xa0;mmol/d)-NSF stone-forming patients and 19 controls (U-Ca 2.5&#xa0;&#xb1;&#xa0;1.4&#xa0;mmol/d)-CG. On days 1 and 5 PTH-,FGF23-,Ca-,P were determined before and after NaP-load. The areas under PTH, FGF23 curves (AUC) were calculated. U-Ca, urinary phosphate (U-P) and sodium (U-Na) were also determined.<br><br>RESULTS: Following NaP-load, patients and controls exhibited expected alterations in Ca-P homeostasis. Despite changes in phosphate and PTH, no differences in FGF23 concentrations were observed. Patients differed from controls in having higher AUCPTH, calciuria and natriuresis, taking longer for PTH and P to normalize and lack of correlation between AUCPTH and phosphaturia. Post-NaP-load hypocalciuric effect of PTH secretion in NSF was less pronounced than in CG. In the HSFs, the hypocalciuric effect was more pronounced than in NSFs, but insufficient to correct hypercalciuria. In all stone-formers with low 25OHD3 concentrations, the AUCFGF23 was significantly increased on first (1215&#xa0;&#xb1;&#xa0;605vs766&#xa0;&#xb1;&#xa0;315 p&#xa0;=&#xa0;0.0457) and fifth days (1211&#xa0;&#xb1;&#xa0;641vs777&#xa0;&#xb1;&#xa0;299 p&#xa0;=&#xa0;0.041) of NaP-load, compared to normal/high 25OHD3-patients. Hypercalciuric patients with low 25OHD3 concentrations had greater AUCPTH5 than those with normal/high 25OHD3 (1005&#xa0;&#xb1;&#xa0;401vs835&#xa0;&#xb1;&#xa0;220 p&#xa0;=&#xa0;0.0341).<br><br>CONCLUSIONS: Compared to controls, kidney-stone-forming patients exhibited enhanced PTH secretion after NaP-load. The HSFs showed a more pronounced hypocalciuric effect than NSFs, but insufficient to correct hypercalciuria. In hypercalciuric stone-formers with low 25OHD3, FGF23 engagement in hyperphosphatemia reduction increased.}, }
@article {pmid32330575, year = {2020}, author = {Islam, AK and Holt, S and Reisch, J and Nwariaku, F and Antonelli, J and Maalouf, NM}, title = {What Predicts Recurrent Kidney Stone after Parathyroidectomy in Patients with Primary Hyperparathyroidism?.}, journal = {Journal of the American College of Surgeons}, volume = {231}, number = {1}, pages = {74-82}, doi = {10.1016/j.jamcollsurg.2020.04.015}, pmid = {32330575}, issn = {1879-1190}, mesh = {Calcium/*metabolism ; Female ; Humans ; Hyperparathyroidism, Primary/complications/diagnosis/*surgery ; Kidney Calculi/*complications/diagnosis/metabolism ; Male ; Middle Aged ; Parathyroidectomy/*methods ; Postoperative Period ; Prognosis ; Recurrence ; Retrospective Studies ; }, abstract = {BACKGROUND: Some, but not all, patients with primary hyperparathyroidism (PHPT) and kidney stone disease (KSD) are cured of their nephrolithiasis after parathyroidectomy. The goal of this study was to identify risk factors for recurrent KSD despite successful parathyroidectomy in known stone formers with PHPT.<br><br>STUDY DESIGN: We conducted a single-center retrospective review of patients presenting to urology clinic with KSD between January 2008 and July 2018, who were diagnosed with concurrent PHPT, and underwent definitive parathyroidectomy. Laboratory testing for serum calcium, PTH (parathyroid hormone), phosphorus and 25-OH-vitamin D, and 24-hour urine studies for volume, pH, calcium, citrate, oxalate, uric acid, sodium, and creatinine was performed pre- and post-parathyroidectomy. Stone recurrence was determined on routine diagnostic imaging or by symptomatic KSD.<br><br>RESULTS: Mean age at parathyroidectomy was 57 &#xb1; 14 years. Pre-parathyroidectomy, mean serum calcium, 24-hour urine calcium, and PTH were 10.6 &#xb1; 0.5 mg/dL, 378 &#xb1; 209 mg/day, and 114 &#xb1; 97 pg/mL, respectively. Twenty-six of 69 patients (38%) had multigland parathyroid disease. After parathyroidectomy, serum calcium and PTH levels normalized in 69 of 69 and 62 of 69 patients, respectively. However, 37 of 69 patients (54%) had persistent hypercalciuria postoperatively, and 16 of 69 (23%) had recurrent KSD, on average, 2.0 &#xb1; 1.6 years after parathyroidectomy. Patients with recurrent KSD post-parathyroidectomy were significantly younger compared with patients without recurrent KSD (51 &#xb1; 15 vs 60 &#xb1; 13 years, p&#xa0;= 0.02). In a logistic regression model, younger age remains a strong predictive factor for recurrent KSD.<br><br>CONCLUSIONS: Nearly one-quarter of PHPT patients with KSD who undergo successful parathyroidectomy present with recurrent KSD despite normalization of serum calcium, and more than half exhibit persistent calciuria. These patients were younger and may require closer monitoring for stone recurrence after successful parathyroidectomy. Further studies are needed to better identify the etiology of KSD post-parathyroidectomy.}, }
@article {pmid32271147, year = {2020}, author = {Kim, OH and Booth, CJ and Choi, HS and Lee, J and Kang, J and Hur, J and Jung, WJ and Jung, YS and Choi, HJ and Kim, H and Auh, JH and Kim, JW and Cha, JY and Lee, YJ and Lee, CS and Choi, C and Jung, YJ and Yang, JY and Im, SS and Lee, DH and Cho, SW and Kim, YB and Park, KS and Park, YJ and Oh, BC}, title = {High-phytate/low-calcium diet is a risk factor for crystal nephropathies, renal phosphate wasting, and bone loss.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32271147}, issn = {2050-084X}, mesh = {Animal Feed/analysis ; Animals ; Bone and Bones/*metabolism ; Calcium/*metabolism ; Calcium, Dietary/*adverse effects ; Diet/adverse effects ; Female ; Male ; Minerals/*metabolism ; Phosphates ; Phosphorus/metabolism ; Phytic Acid/pharmacology ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic/metabolism ; Risk Factors ; }, abstract = {Phosphate overload contributes to mineral bone disorders that are associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and of negligible nutritional value in humans. However, the mechanism and adverse effects of high-phytate intake on Ca[2+] and phosphate absorption and homeostasis are unknown. Here, we show that excessive intake of phytate along with a low-Ca[2+] diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca[2+] supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca[2+]-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca[2+] bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca[2+] diet and is a risk factor for phosphate overloading and for the development of crystal nephropathies and bone disease.}, }
@article {pmid32163150, year = {2020}, author = {Bayomy, O and Zaheer, S and Williams, JS and Curhan, G and Vaidya, A}, title = {Disentangling the Relationships Between the Renin-Angiotensin-Aldosterone System, Calcium Physiology, and Risk for Kidney Stones.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {105}, number = {6}, pages = {1937-1946}, pmid = {32163150}, issn = {1945-7197}, support = {K24 DK091417/DK/NIDDK NIH HHS/United States ; R01 DK107407/DK/NIDDK NIH HHS/United States ; R01 DK115392/DK/NIDDK NIH HHS/United States ; UL1 TR002541/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aldosterone/*metabolism ; Biomarkers/*analysis ; Calcium/*metabolism ; Calcium, Dietary/administration &amp; dosage ; Case-Control Studies ; Cross-Sectional Studies ; Diet, Sodium-Restricted/methods ; Female ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Kidney Calculi/diet therapy/*epidemiology/metabolism/pathology ; Longitudinal Studies ; Male ; Middle Aged ; Prognosis ; *Renin-Angiotensin System ; Risk Factors ; Sodium/urine ; Young Adult ; }, abstract = {CONTEXT: Complex relationships between aldosterone and calcium homeostasis have been proposed.<br><br>OBJECTIVE: To disentangle the influence of aldosterone and intravascular volume on calcium physiology.<br><br>DESIGN: Patient-oriented and epidemiology studies.<br><br>SETTING: Clinical research center and nationwide cohorts.<br><br>PARTICIPANTS/INTERVENTIONS: Patient-oriented study (n&#x2005;=&#x2005;18): Participants were evaluated after completing a sodium-restricted (RES) diet to contract intravascular volume and after a liberalized-sodium (LIB) diet to expand intravascular volume. Cross-sectional studies (n&#x2005;=&#x2005;3755): the association between 24h urinary sodium and calcium excretion and risk for kidney stones was assessed.<br><br>RESULTS: Patient-oriented study: compared to a RES-diet, a LIB-diet suppressed renin activity (LIB: 0.3 [0.1, 0.4] vs. RES: 3.1 [1.7, 5.3] ng/mL/h; P&#x2005;<&#x2005;0.001) and plasma aldosterone (LIB: 2.0 [2.0, 2.7] vs. RES: 20.0 [16.1, 31.0] vs. ng/dL; P&#x2005;<&#x2005;0.001), but increased calciuria (LIB: 238.4&#x2005;&#xb1;&#x2005;112.3 vs. RES: 112.9&#x2005;&#xb1;&#x2005;60.8 mg/24hr; P&#x2005;<&#x2005;0.0001) and decreased serum calcium (LIB: 8.9&#x2005;&#xb1;&#x2005;0.3 vs. RES: 9.8&#x2005;&#xb1;&#x2005;0.4 mg/dL; P&#x2005;<&#x2005;0.0001). Epidemiology study: mean urinary calcium excretion was higher with greater urinary sodium excretion. Compared to a urinary sodium excretion of&#x2005;<&#x2005;120 mEq/day, a urinary sodium excretion of &#x2265;220 mEq/day was associated with a higher risk for having kidney stones in women (risk ratio&#x2005;=&#x2005;1.79 [95% confidence interval 1.05, 3.04]) and men (risk ratio&#x2005;=&#x2005;2.06 [95% confidence interval 1.27, 3.32]).<br><br>CONCLUSIONS: High dietary sodium intake suppresses aldosterone, decreases serum calcium, and increases calciuria and the risk for developing kidney stones. Our findings help disentangle the influences of volume from aldosterone on calcium homeostasis and provide support for the recommendation to restrict dietary sodium for kidney stone prevention.}, }
@article {pmid32127396, year = {2020}, author = {DeLeon, C and Wang, HH and Gunn, J and Wilhelm, M and Cole, A and Arnett, S and Wang, DQ and Arnatt, CK}, title = {A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice.}, journal = {Journal of lipid research}, volume = {61}, number = {5}, pages = {767-777}, pmid = {32127396}, issn = {1539-7262}, support = {R01 DK114516/DK/NIDDK NIH HHS/United States ; P30 DK041296/DK/NIDDK NIH HHS/United States ; R01 DK126369/DK/NIDDK NIH HHS/United States ; R56 DK101793/DK/NIDDK NIH HHS/United States ; R21 AA025737/AA/NIAAA NIH HHS/United States ; R01 DK106249/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism ; Cholesterol/*metabolism ; Cyclic AMP/metabolism ; Estrogens/*pharmacology ; Female ; Gallstones/*chemically induced/metabolism/*prevention &amp; control ; HL-60 Cells ; Humans ; Mice ; Receptors, Estrogen/*antagonists &amp; inhibitors/metabolism ; Receptors, G-Protein-Coupled/*antagonists &amp; inhibitors ; Signal Transduction/drug effects ; }, abstract = {Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα ([-/-]) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.}, }
@article {pmid32111156, year = {2020}, author = {Xie, J and Huang, JS and Huang, XJ and Peng, JM and Yu, Z and Yuan, YQ and Xiao, KF and Guo, JN}, title = {Profiling the urinary microbiome in men with calcium-based kidney stones.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {41}, pmid = {32111156}, issn = {1471-2180}, support = {JCYJ20170307095620828//The Science and Technology Foundation of Shenzhen/International ; }, mesh = {Adult ; Bacteria/*classification/genetics/isolation &amp; purification ; Calcium/metabolism ; Case-Control Studies ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Humans ; Kidney Calculi/metabolism/microbiology/*urine ; Kidney Pelvis/*microbiology ; Male ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; Sex Characteristics ; Urine/chemistry/*microbiology ; }, abstract = {BACKGROUND: The dogma that urine is sterile in healthy individuals has been overturned by recent studies applying molecular-based methods. Mounting evidences indicate that dysbiosis of the urinary microbiota is associated with several urological diseases. In this study, we aimed to investigate the urinary microbiome of male patients with calcium-based kidney stones and compare it with those of healthy individuals.<br><br>RESULTS: The diversity of the urinary microbiota in kidney stone patients was significantly lower than that of healthy controls based on the Shannon and Simpson index (P&#x2009;<&#x2009;0.001 for both indices). The urinary microbiota structure also significantly differed between kidney stone patients and healthy controls (ANOSIM, R&#x2009;=&#x2009;0.11, P&#x2009;<&#x2009;0.001). Differential representation of inflammation associated bacteria (e.g., Acinetobacter) and several enriched functional pathways were identified in the urine of kidney stones patients. Meanwhile, we found the species diversity, overall composition of microbiota and predicted functional pathways were similar between bladder urine and renal pelvis urine in kidney stone patients.<br><br>CONCLUSIONS: A marked dysbiosis of urinary microbiota in male patients with calcium-based kidney stones was observed, which may be helpful to interpret the association between bacteria and calcium-based kidney stones.}, }
@article {pmid32032687, year = {2020}, author = {Schulster, ML and Goldfarb, DS}, title = {Vitamin D and Kidney Stones.}, journal = {Urology}, volume = {139}, number = {}, pages = {1-7}, doi = {10.1016/j.urology.2020.01.030}, pmid = {32032687}, issn = {1527-9995}, mesh = {Animals ; Bone Density/drug effects ; Calcitriol/biosynthesis/metabolism ; Calcium/administration &amp; dosage/*adverse effects/metabolism ; Cohort Studies ; Dietary Supplements/*adverse effects ; Diphosphonates/therapeutic use ; Female ; Humans ; Intestinal Absorption ; Kidney Calculi/chemistry/*etiology/prevention &amp; control ; Male ; Mutation ; Parathyroid Hormone/blood ; Rats ; Receptors, Calcitriol/genetics ; Thiazides/therapeutic use ; Vitamin D/administration &amp; dosage/*adverse effects/metabolism ; Vitamin D Deficiency/therapy ; Vitamin D3 24-Hydroxylase/genetics/metabolism ; Vitamins/administration &amp; dosage/*adverse effects/metabolism ; }, abstract = {This review explores the relationship between vitamin D supplementation and lithogenesis. A causal relationship has been assumed despite myriad studies demonstrating that therapeutic doses of vitamin D do not increase lithogenic risk. Select stone formers may be at increased risk for recurrence with vitamin D supplementation, possibly from CYP24A1 gene mutations. Additionally, the evidence for who is vitamin D deficient, and the benefits of supplementation in those not at risk for rickets, is sparse. Concerns may be avoidable as vitamin D screening appears unnecessary in most patients, and superior pharmacology is available which increases bone density, while decreasing stone formation.}, }
@article {pmid31979185, year = {2020}, author = {Yue, L and Wang, L and Du, Y and Zhang, W and Hamada, K and Matsumoto, Y and Jin, X and Zhou, Y and Mikoshiba, K and Gill, DL and Han, S and Wang, Y}, title = {Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells.}, journal = {Cells}, volume = {9}, number = {2}, pages = {}, pmid = {31979185}, issn = {2073-4409}, support = {R35 GM131916/GM/NIGMS NIH HHS/United States ; }, mesh = {Calcium/*metabolism ; Calcium Signaling ; Cell Movement ; Cell Proliferation ; Endoplasmic Reticulum/*metabolism ; HEK293 Cells ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Nedd4 Ubiquitin Protein Ligases/metabolism ; ORAI1 Protein/metabolism ; Protein Isoforms/metabolism ; }, abstract = {Being the largest the Ca[2+] store in mammalian cells, endoplasmic reticulum (ER)-mediated Ca[2+] signalling often involves both Ca[2+] release via inositol 1, 4, 5-trisphosphate receptors (IP3R) and store operated Ca[2+] entries (SOCE) through Ca[2+] release activated Ca[2+] (CRAC) channels on plasma membrane (PM). IP3Rs are functionally coupled with CRAC channels and other Ca[2+] handling proteins. However, it still remains less well defined as to whether IP3Rs could regulate ER-mediated Ca[2+] signals independent of their Ca[2+] releasing ability. To address this, we generated IP3Rs triple and double knockout human embryonic kidney (HEK) cell lines (IP3Rs-TKO, IP3Rs-DKO), and systemically examined ER Ca[2+] dynamics and CRAC channel activity in these cells. The results showed that the rate of ER Ca[2+] leakage and refilling, as well as SOCE were all significantly reduced in IP3Rs-TKO cells. And these TKO effects could be rescued by over-expression of IP3R3. Further, results showed that the diminished SOCE was caused by NEDD4L-mediated ubiquitination of Orai1 protein. Together, our findings indicate that IP3R3 is one crucial player in coordinating ER-mediated Ca[2+] signalling.}, }
@article {pmid31829950, year = {2019}, author = {Spivacow, FR and Pailler, M and Martínez, P}, title = {[Idiopathic hypercalciuria: can the diuretics be avoided?].}, journal = {Medicina}, volume = {79}, number = {6}, pages = {477-482}, pmid = {31829950}, issn = {1669-9106}, mesh = {Adult ; Aged ; Body Mass Index ; Calcium/blood/urine ; Diuretics/*therapeutic use ; Female ; Follow-Up Studies ; Humans ; Hypercalciuria/*diet therapy/etiology ; Male ; Middle Aged ; Phosphorus/blood/urine ; Reference Values ; Sex Factors ; Time Factors ; Treatment Outcome ; }, abstract = {Idiopathic hypercalciuria is defined as calcium excretion greater than 220 and 300 mg/day in women and men respectively, or greater than 4 mg/kg body weight. In women with osteoporosis it is observed in 19% of cases, while in kidney stones cases varies between 50 and 70%. We selected 206 hypercalciuric patients from our database, with and without renal lithiasis, to whom a restricted diet had been indicated. We divided them, according to the response, into a dependent diet and an independent diet. We considered 122 patients with diagnosis of hypercalciuria diet dependent (105 women and 17 men), which were followed with dietary control (800 mg of calcium, around 1 g of animal proteins and < 100 mEq sodium a day). The appearance of stones, or the recurrence of stones, was not considered, nor was bone involvement. After an average of 17 months, everyone had their calciuria controlled and there were even 16 (13%) who, after 42 months of follow-up, continued to be normocalciuric only on a diet. We conclude that the division of the hypercalciurias is fundamental, according to their response to a restricted diet, in order to avoid or postpone the use of diuretics and its adverse effects, with an adequate management of the diet.}, }
@article {pmid31821850, year = {2020}, author = {Buchalski, B and Wood, KD and Challa, A and Fargue, S and Holmes, RP and Lowther, WT and Knight, J}, title = {The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1866}, number = {3}, pages = {165633}, pmid = {31821850}, issn = {1879-260X}, support = {P30 DK074038/DK/NIDDK NIH HHS/United States ; P30 CA013148/CA/NCI NIH HHS/United States ; R01 DK054468/DK/NIDDK NIH HHS/United States ; P60 DK079626/DK/NIDDK NIH HHS/United States ; K08 DK115833/DK/NIDDK NIH HHS/United States ; R01 DK083527/DK/NIDDK NIH HHS/United States ; P30 AR048311/AR/NIAMS NIH HHS/United States ; P30 CA012197/CA/NCI NIH HHS/United States ; P30 DK056336/DK/NIDDK NIH HHS/United States ; K01 DK114332/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Calcium/metabolism ; Disease Models, Animal ; Female ; Glycolates/*metabolism/*urine ; Humans ; Hydroxyproline/*metabolism ; Hyperoxaluria, Primary/*metabolism ; Kidney/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxalates/*metabolism/*urine ; Oxidoreductases/*metabolism ; Proline Oxidase/metabolism ; }, abstract = {The major clinical manifestation of the Primary Hyperoxalurias (PH) is increased production of oxalate, as a consequence of genetic mutations that lead to aberrant glyoxylate and hydroxyproline metabolism. Hyperoxaluria can lead to the formation of calcium-oxalate kidney stones, nephrocalcinosis and renal failure. Current therapeutic approaches rely on organ transplants and more recently modifying the pathway of oxalate synthesis using siRNA therapy. We have recently reported that the metabolism of trans-4-hydroxy-L-proline (Hyp), an amino acid derived predominantly from collagen metabolism, is a significant source of oxalate production in individuals with PH2 and PH3. Thus, the first enzyme in the Hyp degradation pathway, hydroxyproline dehydrogenase (HYPDH), represents a promising therapeutic target for reducing endogenous oxalate production in these individuals. This is supported by the observation that individuals with inherited mutations in HYPDH (PRODH2 gene) have no pathological consequences. The creation of mouse models that do not express HYPDH will facilitate research evaluating HYPDH as a target. We describe the phenotype of the Prodh2 knock out mouse model and show that the lack of HYPDH in PH mouse models results in lower levels of urinary oxalate excretion, consistent with our previous metabolic tracer and siRNA-based knockdown studies. The double knockout mouse, Grhpr KO (PH2 model) and Prodh2 KO, prevented calcium-oxalate crystal deposition in the kidney, when placed on a 1% Hyp diet. These observations support the use of the Grhpr KO mice to screen HYPDH inhibitors in vivo. Altogether these data support HYPDH as an attractive therapeutic target for PH2 and PH3 patients.}, }
@article {pmid31789849, year = {2020}, author = {Beara-Lasic, L and Goldfarb, DS}, title = {Nephrolithiasis in women: how different from men?.}, journal = {Current opinion in nephrology and hypertension}, volume = {29}, number = {2}, pages = {201-206}, doi = {10.1097/MNH.0000000000000577}, pmid = {31789849}, issn = {1473-6543}, mesh = {Adolescent ; Calcium/metabolism ; Female ; Humans ; Male ; Nephrolithiasis/*epidemiology/etiology ; Pregnancy ; Prevalence ; Sex Characteristics ; }, abstract = {PURPOSE OF REVIEW: Men have more kidney stones compared with women; however, the difference is progressively decreasing. The reasons for higher prevalence of stones in men, as well as increasing prevalence in women, is a subject of ongoing speculation. In this review, we summarize the evidence of differences between men and women and expand on the speculative causes.<br><br>RECENT FINDINGS: Stone incidence is rising in women and adolescent girls. Stone disease is more heritable among men than women, and women demonstrate greater influence of the unique environment. Women under the age of 50 years who have been pregnant, have more than double the odds of kidney stones compared with those who have never been pregnant. Women are more burdened with obesity, bariatric surgery and dieting, all associated with increased stones. Women have higher urinary pH because of greater absorption of dietary organic anions leading to increased urinary citrate, compared with men, and they differ in tubular calcium handling.<br><br>SUMMARY: It is obvious that the cause of stones in men and women is complex and requires further study. Potential clues offered are in the change of the female environment, influencing increasing incidence in stones, particularly of younger women and female adolescents.}, }
@article {pmid31759903, year = {2020}, author = {De Ruysscher, C and Pien, L and Tailly, T and Van Laecke, E and Vande Walle, J and Prytuła, A}, title = {Risk factors for recurrent urolithiasis in children.}, journal = {Journal of pediatric urology}, volume = {16}, number = {1}, pages = {34.e1-34.e9}, doi = {10.1016/j.jpurol.2019.09.021}, pmid = {31759903}, issn = {1873-4898}, mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Kidney Calculi/*epidemiology ; Male ; Recurrence ; Retrospective Studies ; Risk Factors ; }, abstract = {PURPOSE: To identify risk factors associated with recurrent kidney stones in a paediatric cohort in a Belgian tertiary centre.<br><br>STUDY DESIGN AND METHODS: Medical records of children with the first episode of urolithiasis between 1998 and 2016, followed at Ghent University Hospital initially and at least one-year follow-up were retrospectively reviewed. Patient characteristics, past medical history, presenting symptoms, the results of laboratory investigations and the applied management strategy were analysed. The significant variables from the univariate analysis were integrated into a backward conditional multivariate model.<br><br>RESULTS: Ninety-seven children were included in the analysis, of which 33 (34%) presented with at least one episode of stone recurrence. In the univariate analysis, body mass index (BMI)&#xa0;>&#xa0;85th percentile and asymptomatic stones at initial presentation were associated with 1.8 and 0.1 times lower risk of recurrent stones, respectively (p&#xa0;=&#xa0;0.020, 95% confidence interval (CI):0.368-8.749 and p&#xa0;=&#xa0;0.017, 95% CI:0.014-0.921). In contrast, immobilization resulted in a 10-times higher risk (p&#xa0;=&#xa0;0.002, 95% CI:1.968-50.005) and the need for technical intervention was associated with a 3.2- times higher risk (p&#xa0;=&#xa0;0.017, 95% CI:1.297-8.084) of developing recurrent stones. On multivariate analysis only BMI >85th percentile was associated with a 15 times lower risk of stone recurrence (p&#xa0;=&#xa0;0.030, 95% CI:0.006-0.739).<br><br>DISCUSSION: A possible explanation of reduced risk in patients with a BMI&#xa0;>&#xa0;85th percentile may lie in a different metabolic profile. Immobilization as a risk factor can be explained by calcium metabolism, which is influenced by immobilization due to fractures, paralysis or motor disability because it causes resorption of the skeleton resulting in elevated blood calcium levels. This study showed that patients who presented without symptoms when the stones first occurred were less likely to have recurring kidney stones compared with patients with symptoms at initial presentation. When technical intervention was needed, we believe this is partly due to a larger stone burden, however we could not find an evidence-based explanation. The institutional protocol, which allowed to create a database with a limited number of patients, was lost to follow-up. Despite the retrospective setting some data were missing. There might also be a bias because the patients were followed-up at a tertiary centre. Possibly, our conclusions cannot be generalized toward&#xa0;the entire paediatric population.<br><br>CONCLUSION: Of all the factors investigated in our cohort, BMI&#xa0;>85&#xa0;th percentile and asymptomatic stones are associated with a lower risk of stone recurrence. Conversely, immobilized patients and those who require technical intervention at initial presentation may benefit from an intense follow-up after the first episode of urolithiasis.}, }
@article {pmid31754202, year = {2019}, author = {Chen, WC and Chou, WH and Chu, HW and Huang, CC and Liu, X and Chang, WP and Chou, YH and Chang, WC}, title = {The rs1256328 (ALPL) and rs12654812 (RGS14) Polymorphisms are Associated with Susceptibility to Calcium Nephrolithiasis in a Taiwanese population.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {17296}, pmid = {31754202}, issn = {2045-2322}, support = {MOST105-2628-B-038-001-MY4//Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)/International ; MOST105-2628-B-038-001-MY4//Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)/International ; MOST105-2628-B-038-001-MY4//Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)/International ; MOST105-2628-B-038-001-MY4//Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan)/International ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Alkaline Phosphatase/*genetics ; Calcium/*metabolism ; Case-Control Studies ; Female ; *Genetic Predisposition to Disease ; Humans ; Hydrogen-Ion Concentration ; Kidney Calculi/chemistry/epidemiology/*genetics/urine ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prevalence ; RGS Proteins/*genetics ; Receptors, Calcium-Sensing/genetics/metabolism ; Signal Transduction/genetics ; Taiwan/epidemiology ; Young Adult ; }, abstract = {Nephrolithiasis is a common disease affecting almost all populations, with an increasing prevalence over the past decades. Previous studies revealed several functional polymorphisms associated with the pathogenesis of nephrolithiasis. However, data on Asian populations are limited. In this study, three candidate polymorphisms were selected from previous studies to investigate the correlations with nephrolithiasis in a Taiwanese population. In total, 454 nephrolithiasis patients were recruited from Kaohsiung Medical University Hospital, with SNP frequency for 1513 subjects of general population from the Taiwan Biobank (TWB) as a genotypic reference. Results revealed that subjects with minor TT genotype at rs1256328 (alkaline phosphatase, liver/bone/kidney (ALPL)) have higher susceptibility to nephrolithiasis (odds ratio (OR) = 2.03, p = 0.0013). In addition, subjects carrying the minor AA genotype at rs12654812 (regulator of G protein signaling 14 (RGS14)) have higher susceptibility to nephrolithiasis (OR = 1.91, p = 0.0017). Among nephrolithiasis patients, subjects with GG at rs7627468 (calcium-sensing receptor (CASR)) have lower pH level in urine (p = 0.0088). Importantly, rs7627468 is associated with the expressions of IQCB1 and EAF2. rs12654812 could influence the expression of RGS14 itself, MXD3, and FGFR4. In summary, this study successfully validated the genetic roles of rs1256328 and rs12654812 in human nephrolithiasis.}, }
@article {pmid31729369, year = {2019}, author = {Howles, SA and Wiberg, A and Goldsworthy, M and Bayliss, AL and Gluck, AK and Ng, M and Grout, E and Tanikawa, C and Kamatani, Y and Terao, C and Takahashi, A and Kubo, M and Matsuda, K and Thakker, RV and Turney, BW and Furniss, D}, title = {Genetic variants of calcium and vitamin D metabolism in kidney stone disease.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {5175}, pmid = {31729369}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/N001524/1/MRC_/Medical Research Council/United Kingdom ; 204826/z/16/z//Wellcome Trust (Wellcome)/International ; 106995/z/15/z//Wellcome Trust (Wellcome)/International ; }, mesh = {Adult ; Aged ; Asian People/genetics ; Calcium/*metabolism ; Diacylglycerol Kinase/genetics/metabolism ; Female ; Genetic Variation ; Genome-Wide Association Study ; Genotype ; Humans ; Japan ; Kidney Calculi/*genetics/metabolism ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prospective Studies ; Proteins/genetics/metabolism ; Receptors, Calcium-Sensing/genetics/metabolism ; United Kingdom ; Vitamin D/*metabolism ; White People/genetics ; }, abstract = {Kidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a heritability of ~45-60%. We present genome-wide association studies in British and Japanese populations and a trans-ethnic meta-analysis that include 12,123 cases and 417,378 controls, and identify 20 nephrolithiasis-associated loci, seven of which are previously unreported. A CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of only nephrolithiasis patients, the CYP24A1-associated locus correlates with serum calcium concentration and a number of nephrolithiasis episodes while the DGKD-associated locus correlates with urinary calcium excretion. In vitro, DGKD knockdown impairs CaSR-signal transduction, an effect rectified with the calcimimetic cinacalcet. Our findings indicate that studies of genotype-guided precision-medicine approaches, including withholding vitamin D supplementation and targeting vitamin D activation or CaSR-signaling pathways in patients with recurrent kidney stones, are warranted.}, }
@article {pmid31710081, year = {2019}, author = {Dong, D and Hao, Q and Zhang, P and Wang, T and Han, F and Liang, X and Fei, Z}, title = {Endoplasmic reticulum Ca2+ release causes Rieske iron-sulfur protein-mediated mitochondrial ROS generation in pulmonary artery smooth muscle cells.}, journal = {Bioscience reports}, volume = {39}, number = {12}, pages = {}, pmid = {31710081}, issn = {1573-4935}, mesh = {Animals ; Calcium/*metabolism ; Electron Transport Complex III/genetics/*metabolism ; Endoplasmic Reticulum/genetics/*metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Mitochondria/genetics/*metabolism/pathology ; Mitochondrial Proteins/genetics/*metabolism ; Muscle, Smooth, Vascular/*metabolism/pathology ; Myocytes, Smooth Muscle/*metabolism/pathology ; Pulmonary Artery/*metabolism/pathology ; Reactive Oxygen Species/*metabolism ; }, abstract = {Mitochondrial reactive oxygen species (ROS) cause Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptors (RyRs) in pulmonary artery smooth muscle cells (PASMCs), playing an essential role in hypoxic pulmonary vasoconstriction (HPV). Here we tested a novel hypothesis that hypoxia-induced RyR-mediated Ca2+ release may, in turn, promote mitochondrial ROS generation contributing to hypoxic cellular responses in PASMCs. Our data reveal that application of caffeine to elevate intracellular Ca2+ concentration ([Ca2+]i) by activating RyRs results in a significant increase in ROS production in cytosol and mitochondria of PASMCs. Norepinephrine to increase [Ca2+]i due to the opening of inositol 1,4,5-triphosphate receptors (IP3Rs) produces similar effects. Exogenous Ca2+ significantly increases mitochondrial-derived ROS generation as well. Ru360 also inhibits the hypoxic ROS production. The RyR antagonist tetracaine or RyR2 gene knockout (KO) suppresses hypoxia-induced responses as well. Inhibition of mitochondrial Ca2+ uptake with Ru360 eliminates N- and Ca2+-induced responses. RISP KD abolishes the hypoxia-induced ROS production in mitochondria of PASMCs. Rieske iron-sulfur protein (RISP) gene knockdown (KD) blocks caffeine- or NE-induced ROS production. Taken together, these findings have further demonstrated that ER Ca2+ release causes mitochondrial Ca2+ uptake and RISP-mediated ROS production; this novel local ER/mitochondrion communication-elicited, Ca2+-mediated, RISP-dependent ROS production may play a significant role in hypoxic cellular responses in PASMCs.}, }
@article {pmid31690714, year = {2019}, author = {Yang, A and Guo, H and Fu, M and Liu, M}, title = {Inhibitive Effects of Huashi Pill on Formation of Renal Stones by Modulating Urine Biochemical Indexes and Osteopontin in Renal Stone Rat Models.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {25}, number = {}, pages = {8335-8344}, pmid = {31690714}, issn = {1643-3750}, mesh = {Animals ; Blood Urea Nitrogen ; Calcium/metabolism ; China ; Disease Models, Animal ; Drugs, Chinese Herbal/*pharmacology ; Kidney/drug effects ; Kidney Calculi/*drug therapy ; Male ; Medicine, Chinese Traditional/methods ; Osteopontin/*drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Uric Acid/metabolism ; }, abstract = {BACKGROUND Renal stones are the accumulated or deposited crystals that form and appear in supersaturated urine. This study aimed to the investigate the therapeutic effects of Huashi Pill on clearance of renal stones. MATERIAL AND METHODS Sprague Dawley rats were divided into normal control, positive control, low-dosage Huashi Pill, medium-dosage Huashi Pill, and high-dosage Huashi Pill groups. A renal rat model was established by using ethylene glycol, ammonium chloride, and calcium gluconate. The urinary pH, urine protein, and uric acid levels, as well as the calcium, magnesium, and phosphorus levels were examined. The blood urea nitrogen (BUN) and creatinine (Cr) levels were also evaluated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) levels were evaluated. Crystal formation and calcium deposits were examined using hematoxylin and eosin (H and E) staining and von Kossa staining, respectively. Osteopontin (OPN) expression was evaluated with quantitative real-time polymerase chain reaction assay and immunohistochemical assay. RESULTS A renal stone rat model was successfully established. Huashi Pill significantly improved water and food intake and enhanced pH value of urine (P<0.05). Huashi Pill significantly improved the liver functions by decreasing ALT and TBIL levels (P<0.05). Huashi Pill regulated the amounts of microelements. Huashi Pill significantly decreased the urine protein, uric acid, and Cr levels (P<0.05). Huashi Pill inhibited formation of stone crystals and reduced the insoluble calcium deposition. Huashi Pill significantly downregulated expression of OPN in the kidney tissues of renal rat models (P<0.05). CONCLUSIONS Huashi Pill inhibited stone formation by regulating urine biochemical indexes and reducing OPN expression in kidney tissue in a renal stone rat model.}, }
@article {pmid31626518, year = {2019}, author = {Qin, J and Cai, Z and Xing, J and Duan, B and Bai, P}, title = {Association between calcitonin receptor gene polymorphisms and calcium stone urolithiasis: A meta-analysis.}, journal = {International braz j urol : official journal of the Brazilian Society of Urology}, volume = {45}, number = {5}, pages = {901-909}, pmid = {31626518}, issn = {1677-6119}, mesh = {Calcium/metabolism ; Female ; Genetic Association Studies ; Humans ; Male ; *Polymorphism, Single Nucleotide ; Receptors, Calcitonin/*genetics ; Risk Assessment ; Risk Factors ; Urolithiasis/*genetics ; }, abstract = {PURPOSE: It has been reported that calcitonin receptor (CALCR) gene polymorphisms might be associated with calcium stone urolithiasis. Owing to mixed and inconclusive results, we conducted a meta-analysis to summarize and clarify this association.<br><br>MATERIALS AND METHODS: A systematic search of studies on the association between CALCR gene polymorphisms and calcium stone urolithiasis susceptibility was conducted in databases.<br><br>RESULTS: Odds ratios and 95% confi dence intervals were used to pool the effect size. Five articles were included in our meta-analysis.<br><br>CONCLUSIONS: CALCR rs1801197 might be associated with increased risk of calcium stone urolithiasis. There is insufficient data to fully confirm the association between CALCR rs1042138 and calcium stone urolithiasis susceptibility. Well-designed studies with larger sample size and more subgroups are required to validate the risk identified in the current meta-analysis.}, }
@article {pmid31595783, year = {2019}, author = {Roche, EC and Redmond, EJ and Yap, LC and Manecksha, RP}, title = {Seasonal Variation in the Frequency of Presentation with Acute Ureteral Colic and Its Association with Meteorologic Factors.}, journal = {Journal of endourology}, volume = {33}, number = {12}, pages = {1046-1050}, doi = {10.1089/end.2019.0400}, pmid = {31595783}, issn = {1557-900X}, mesh = {Adult ; Aged ; Climate ; Emergency Service, Hospital ; Female ; Humans ; Incidence ; Ireland/epidemiology ; Male ; Middle Aged ; Renal Colic/complications/diagnostic imaging/*epidemiology ; Seasons ; Tomography, X-Ray Computed ; Ureteral Calculi/complications/diagnostic imaging/*epidemiology ; }, abstract = {Introduction: A seasonal variation in the frequency of acute stone presentations has been observed in studies from the United States, Africa, and Asia. The increased incidence of acute stone presentations during periods of warm weather has been attributed to both the dehydrating effect of elevated temperatures and the vitamin D related increase in calciuria during periods of increased sunshine. The aim of this study is to establish whether the association between various meteorologic parameters and the frequency of acute stone presentations also exists in a European climate. Methods: All computed tomography kidneys, ureters and bladder scans performed by Emergency Departments within the Dublin Midland Hospital Group between June 2017 and September 2018 were identified from the national radiologic database. The date of scan in addition to stone parameters (site, size, and side) was recorded. These data were then correlated with weather recordings obtained from the Irish meteorologic office. Results: A total of 2441 patients were investigated for suspected renal colic during the study period of which 781 were confirmed to have ureteral stones. An increased frequency of acute stone presentations was observed during the summer months of both years (June, July, and August). Unexpectedly, the heat wave of summer 2018 was not associated with an increased frequency of nephrolithiasis compared with summer 2017. Conclusion: There is an increased frequency of acute nephrolithiasis during the summer months in Ireland. Health care services should be tailored to expect an increase in service needs during these periods of increased activity.}, }
@article {pmid31472005, year = {2019}, author = {Anglani, F and Gianesello, L and Beara-Lasic, L and Lieske, J}, title = {Dent disease: A window into calcium and phosphate transport.}, journal = {Journal of cellular and molecular medicine}, volume = {23}, number = {11}, pages = {7132-7142}, pmid = {31472005}, issn = {1582-4934}, support = {U54 DK083908/DK/NIDDK NIH HHS/United States ; U54DK83908/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Dent Disease/metabolism/*pathology ; Humans ; Ion Channels/*metabolism ; Ion Transport ; Phosphates/*metabolism ; }, abstract = {This review examines calcium and phosphate transport in the kidney through the lens of the rare X-linked genetic disorder Dent disease. Dent disease type 1 (DD1) is caused by mutations in the CLCN5 gene encoding ClC-5, a Cl[-] /H[+] antiporter localized to early endosomes of the proximal tubule (PT). Phenotypic features commonly include low molecular weight proteinuria (LMWP), hypercalciuria, focal global sclerosis and chronic kidney disease; calcium nephrolithiasis, nephrocalcinosis and hypophosphatemic rickets are less commonly observed. Although it is not surprising that abnormal endosomal function and recycling in the PT could result in LMWP, it is less clear how ClC-5 dysfunction disturbs calcium and phosphate metabolism. It is known that the majority of calcium and phosphate transport occurs in PT cells, and PT endocytosis is essential for calcium and phosphorus reabsorption in this nephron segment. Evidence from ClC-5 KO models suggests that ClC-5 mediates parathormone endocytosis from tubular fluid. In addition, ClC-5 dysfunction alters expression of the sodium/proton exchanger NHE3 on the PT apical surface thus altering transcellular sodium movement and hence paracellular calcium reabsorption. A potential role for NHE3 dysfunction in the DD1 phenotype has never been investigated, either in DD models or in patients with DD1, even though patients with DD1 exhibit renal sodium and potassium wasting, especially when exposed to even a low dose of thiazide diuretic. Thus, insights from the rare disease DD1 may inform possible underlying mechanisms for the phenotype of hypercalciuria and idiopathic calcium stones.}, }
@article {pmid31471161, year = {2019}, author = {van der Wijst, J and van Goor, MK and Schreuder, MF and Hoenderop, JG}, title = {TRPV5 in renal tubular calcium handling and its potential relevance for nephrolithiasis.}, journal = {Kidney international}, volume = {96}, number = {6}, pages = {1283-1291}, doi = {10.1016/j.kint.2019.05.029}, pmid = {31471161}, issn = {1523-1755}, mesh = {Calcium/*metabolism ; Humans ; Kidney Tubules/*metabolism ; Nephrolithiasis/*genetics/metabolism ; Polymorphism, Single Nucleotide ; Protein Conformation ; TRPV Cation Channels/chemistry/*genetics/metabolism ; }, abstract = {Nephrolithiasis or renal stone disease is an increasingly common problem, and its relatively high recurrence rate demands better treatment options. The majority of patients with nephrolithiasis have stones that contain calcium (Ca[2+]), which develop upon "supersaturation" of the urine with insoluble Ca[2+] salts; hence processes that influence the delivery and renal handling of Ca[2+] may influence stone formation. Idiopathic hypercalciuria is indeed frequently observed in patients with kidney stones that contain Ca[2+]. Genetic screens of nephrolithiasis determinants have identified an increasing number of gene candidates, most of which are involved in renal Ca[2+] handling. This review provides an outline of the current knowledge regarding genetics of nephrolithiasis and will mainly focus on the epithelial Ca[2+] channel transient receptor potential vanilloid 5 (TRPV5), an important player in Ca[2+] homeostasis. Being a member of the TRP family of ion channels, TRPV5 is currently part of a revolution in structural biology. Recent technological breakthroughs in the cryo-electron microscopy field, combined with improvements in biochemical sample preparation, have resulted in high-resolution 3-dimensional structural models of integral membrane proteins, including TRPV5. These models currently are being used to explore the proteins' structure-function relationship, elucidate the molecular mechanisms of channel regulation, and study the putative effects of disease variants. Combined with other multidisciplinary approaches, this approach may open an avenue toward better understanding of the pathophysiological mechanisms involved in hypercalciuria and stone formation, and ultimately it may facilitate prevention of stone recurrence through the development of effective drugs.}, }
@article {pmid31416104, year = {2019}, author = {Schöfl, C}, title = {[Update - Calcium Metabolism].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {144}, number = {16}, pages = {1125-1132}, doi = {10.1055/a-0833-9674}, pmid = {31416104}, issn = {1439-4413}, mesh = {*Calcium/metabolism/physiology ; *Calcium Metabolism Disorders ; *Calcium, Dietary/analysis/metabolism ; Humans ; Hypoparathyroidism ; Vitamin D ; }, abstract = {A finely balanced control system keeps the extracellular calcium concentration within narrow limits. Disorders of calcium metabolism are often based on altered parathormone levels. Symptoms are not always clear, sometimes they are even missing: the more it is important to know possible associated diseases. The author presents basics, current diagnostics and concrete therapy options. Central hormone for the regulation of the calcium balance is the parathyroid hormone. With decreasing calcium, PTH leads to an increase in extracellular free calcium concentration in three ways. The classic symptoms of pHPT (polyuria, polydipsia, "stone, leg, and stomach pain") are rare now, as the condition is diagnosed much earlier. Treatment of choice in all symptomatic patients with pHPT is surgery. FHH and pHPT are both characterized by hypercalcaemia and increased parathyroid hormone. The differential diagnosis of urinary calcium excretion, which is usually lower in FHH but normal or elevated in pHPT, is crucial. In primary hypoparathyroidism, parathyroid failure interferes with calcium homeostasis at a central location. Consequences are hypocalcaemia, hyperphosphatemia and lack of active vitamin D. Due to increased urinary calcium excretion, patients with ADH are at high risk for kidney stones, nephrocalcinosis and the development of renal insufficiency. Recently, rhPTH 1-84 has been available for the treatment of hypoparathyroidism. However, long-term data is still lacking to provide a safe indication, considering potential effects and side effects.}, }
@article {pmid31310771, year = {2019}, author = {Bejan, CA and Lee, DJ and Xu, Y and Hsi, RS}, title = {Performance of a Natural Language Processing Method to Extract Stone Composition From the Electronic Health Record.}, journal = {Urology}, volume = {132}, number = {}, pages = {56-62}, pmid = {31310771}, issn = {1527-9995}, support = {UL1 TR002243/TR/NCATS NIH HHS/United States ; }, mesh = {Case-Control Studies ; *Electronic Health Records ; Female ; Humans ; Kidney Calculi/*chemistry ; Male ; *Natural Language Processing ; }, abstract = {OBJECTIVES: To demonstrate the utility of a natural language processing (NLP) algorithm for mining kidney stone composition in a large-scale electronic health records (EHR) repository.<br><br>METHODS: We developed StoneX, a pattern-matching method for extracting kidney stone composition information from clinical notes. We trained the extraction algorithm on manually annotated text mentions of calcium oxalate monohydrate, calcium oxalate dihydrate, hydroxyapatite, brushite, uric acid, and struvite stones. We employed StoneX to identify patients with kidney stone composition data and mine >125 million notes from our institutional EHR. Analyses performed on the extracted patients included stone type conversions over time, survival analysis from a second stone surgery, and disease associations by stone composition to validate the phenotyping method against known associations.<br><br>RESULTS: The NLP algorithm identified 45,235 text mentions corresponding to 11,585 patients. Overall, the system achieved positive predictive value >90% for calcium oxalate monohydrate, calcium oxalate dihydrate, hydroxyapatite, brushite, and struvite; except for uric acid (positive predictive value&#x202f;=&#x202f;87.5%). Survival analysis from a second stone surgery showed statistically significant differences among stone types (P&#x202f;=&#x202f;.03). Several phenotype associations were found: uric acid-type 2 diabetes (odds ratio, OR&#x202f;=&#x202f;2.69, 95% confidence intervals, CI&#x202f;=&#x202f;1.91-3.79), struvite-neurogenic bladder (OR&#x202f;=&#x202f;12.27, 95% CI&#x202f;=&#x202f;4.33-34.79), struvite-urinary tract infection (OR&#x202f;=&#x202f;7.36, 95% CI&#x202f;=&#x202f;3.01-17.99), hydroxyapatite-pulmonary collapse (OR&#x202f;=&#x202f;3.67, 95% CI&#x202f;=&#x202f;2.10-6.42), hydroxyapatite-neurogenic bladder (OR&#x202f;=&#x202f;5.23, 95% CI&#x202f;=&#x202f;2.05-13.36), brushite-calcium metabolism disorder (OR&#x202f;=&#x202f;4.59, 95% CI&#x202f;=&#x202f;2.14-9.81), and brushite-hypercalcemia (OR&#x202f;=&#x202f;4.09, 95% CI&#x202f;=&#x202f;1.90-8.80).<br><br>CONCLUSION: NLP extraction of kidney stone composition from large-scale EHRs is feasible with high precision, enabling high-throughput epidemiological studies of kidney stone disease. These tools will enable high fidelity kidney stone research from the EHR.}, }
@article {pmid31276858, year = {2019}, author = {Anract, J and Baures, M and Barry Delongchamps, N and Capiod, T}, title = {Microcalcifications, calcium-sensing receptor, and cancer.}, journal = {Cell calcium}, volume = {82}, number = {}, pages = {102051}, doi = {10.1016/j.ceca.2019.06.005}, pmid = {31276858}, issn = {1532-1991}, mesh = {Animals ; Calcinosis/*metabolism/pathology ; Calcium/*metabolism ; Calculi/*metabolism/pathology ; Humans ; Inflammation/*metabolism/pathology ; Male ; Neoplasms/*metabolism/pathology ; Prostate/*metabolism/pathology ; Prostatic Hyperplasia/*metabolism/pathology ; Receptors, Calcium-Sensing/metabolism ; Signal Transduction ; }, abstract = {Calcium stones and calculi are observed in numerous human tissues. They are the result of deposition of calcium salts and are due to high local calcium concentrations. Prostatic calculi are usually classified as endogenous or extrinsic stones. Endogenous stones are commonly caused by obstruction of the prostatic ducts around an enlarged prostate resulting from benign prostatic hyperplasia or from chronic inflammation. The latter occurs mainly around the urethra and is generally caused by reflux of urine into the prostate. Calcium concentrations higher than in the plasma at sites of infection may induce the chemotactic response that eventually leads to recruitment of inflammatory cells. The calcium sensing receptor (CaSR) may be crucial for this recruitment as its expression and activity are increased by cytokines such as IL-6 and high extracellular calcium concentrations, respectively. The links between calcium calculi, inflammation, calcium supplementation, and CaSR functions in prostate cancer patients will be discussed in this review.}, }
@article {pmid31250859, year = {2019}, author = {Sun, XY and Zhang, H and Liu, J and Ouyang, JM}, title = {Repair activity and crystal adhesion inhibition of polysaccharides with different molecular weights from red algae Porphyra yezoensis against oxalate-induced oxidative damage in renal epithelial cells.}, journal = {Food &amp; function}, volume = {10}, number = {7}, pages = {3851-3867}, doi = {10.1039/c8fo02556h}, pmid = {31250859}, issn = {2042-650X}, mesh = {Acute Kidney Injury/chemically induced/*drug therapy/prevention &amp; control ; Calcium/metabolism ; Cell Cycle/drug effects ; Cell Line ; Cell Survival/drug effects ; Epithelial Cells/*drug effects ; Humans ; Kidney Calculi/prevention &amp; control ; Membrane Potential, Mitochondrial/drug effects ; Molecular Weight ; Oxalates/*adverse effects ; Oxidation-Reduction ; Oxidative Stress/*drug effects ; Polysaccharides/*chemistry/*pharmacology ; Porphyra/*chemistry ; Reactive Oxygen Species/metabolism ; }, abstract = {Renal epithelial cell injury is a key step in inducing kidney stone formation. However, research on the role of cell repair in the prevention and treatment of kidney stones is limited. In this study, the repair effect of degraded Porphyra yezoensis polysaccharide (PYP) on oxidative stress-mediated intracellular damage triggered by oxalate in human kidney proximal tubular epithelial (HK-2) cells was investigated, and the influence of molecular weight (Mw) on the repair ability of PYP was elucidated. Polysaccharides with different Mws were prepared by degrading PYP with hydrogen peroxide. Four degraded fractions, namely, PYP1, PYP2, PYP3, and PYP4, were successfully obtained with Mws of 576.2, 49.54, 12.65, and 4.020 kDa, respectively. A damaged cell model was established using 2.6 mmol L-1 oxalate to injure HK-2 cells. Various Mws of PYPs were used to repair the damaged cells. The repair mechanism of PYPs against oxalate-induced oxidative stress was examined by evaluating cell proliferation and physiological function recovery. Our study revealed that PYPs increased the viability of oxalate-injured HK-2 cells and restored their morphological characteristics and cytoskeleton. PYPs reduced the levels of oxalate-mediated lactase dehydrogenase release, reactive oxygen species generation, and intracellular Ca2+, the loss of mitochondrial membrane potential, the number of cells arrested in S phase, the expression of 8-hydroxy-desoxyguanosine and poly ADP ribose polymerase, lysosomal damage, and the number of apoptotic cells. The PYP fraction with low Mw presented an increased repair activity against cellular damage induced by oxalate. The resistance of the repaired renal cells to crystal adhesion and aggregation was stronger than that of the damaged cells. PYPs might inhibit the formation of kidney stones by repairing damaged cells and inhibiting crystal adhesion and aggregation. We concluded that PYP with low Mw could be used as a potential therapeutic agent against renal stone formation and recurrence.}, }
@article {pmid31217461, year = {2019}, author = {Rose, E and Lee, D and Xiao, E and Zhao, W and Wee, M and Cohen, J and Bergwitz, C}, title = {Endocrine regulation of MFS2 by branchless controls phosphate excretion and stone formation in Drosophila renal tubules.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {8798}, pmid = {31217461}, issn = {2045-2322}, support = {K08 DK078361/DK/NIDDK NIH HHS/United States ; P30 DK079310/DK/NIDDK NIH HHS/United States ; R01 GM084947/GM/NIGMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism ; Diet ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*metabolism ; Endocrine System/*metabolism ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors/administration &amp; dosage/*metabolism ; Humans ; Hyperphosphatemia/pathology ; Kidney Calculi/*pathology ; Kidney Tubules/*pathology ; Malpighian Tubules/pathology/ultrastructure ; Microinjections ; Microspheres ; Phosphates/blood/*metabolism ; RNA Interference ; Temperature ; }, abstract = {How inorganic phosphate (Pi) homeostasis is regulated in Drosophila is currently unknown. We here identify MFS2 as a key Pi transporter in fly renal (Malpighian) tubules. Consistent with its role in Pi excretion, we found that dietary Pi induces MFS2 expression. This results in the formation of Malpighian calcium-Pi stones, while RNAi-mediated knockdown of MFS2 increases blood (hemolymph) Pi and decreases formation of Malpighian tubule stones in flies cultured on high Pi medium. Conversely, microinjection of adults with the phosphaturic human hormone fibroblast growth factor 23 (FGF23) induces tubule expression of MFS2 and decreases blood Pi. This action of FGF23 is blocked by genetic ablation of MFS2. Furthermore, genetic overexpression of the fly FGF branchless (bnl) in the tubules induces expression of MFS2 and increases Malpighian tubule stones suggesting that bnl is the endogenous phosphaturic hormone in adult flies. Finally, genetic ablation of MFS2 increased fly life span, suggesting that Malpighian tubule stones are a key element whereby high Pi diet reduces fly longevity previously reported by us. In conclusion, MFS2 mediates excretion of Pi in Drosophila, which is as in higher species under the hormonal control of FGF-signaling.}, }
@article {pmid31082531, year = {2019}, author = {Imani Rad, H and Peeri, H and Amani, M and Mohammadnia, A and Ogunniyi, AD and Khazandi, M and Venter, H and Arzanlou, M}, title = {Allicin prevents the formation of Proteus-induced urinary crystals and the blockage of catheter in a bladder model in vitro.}, journal = {Microbial pathogenesis}, volume = {132}, number = {}, pages = {293-301}, doi = {10.1016/j.micpath.2019.05.016}, pmid = {31082531}, issn = {1096-1208}, mesh = {Calcium/metabolism ; Crystallization ; Disulfides ; Dose-Response Relationship, Drug ; Humans ; Hydrogen-Ion Concentration ; Magnesium/metabolism ; Microbial Sensitivity Tests ; Proteus/*drug effects/growth &amp; development ; Proteus Infections/*prevention &amp; control ; Proteus mirabilis/drug effects/growth &amp; development ; Sulfinic Acids/*pharmacology ; Urease ; Urinary Bladder/*microbiology ; Urinary Tract Infections/microbiology/prevention &amp; control ; Urine ; }, abstract = {Stone formation and catheter blockage are major complications of Proteus UTIs. In this study, we investigated the ability of allicin to inhibit P. mirabilis-induced struvite crystallization and catheter blockage using a synthetic bladder model. Struvite crystallization inhibition study was carried out using P. mirabilis lysate as urease enzyme source in synthetic urine (SU). Struvite productions were monitored by phase contrast light microscopy and measurements of pH, Mg[2+] and Ca[2+] precipitation and turbidity. A catheter blockage study was performed in a synthetic bladder model mimicking natural UTI in the presence of allicin at sub-MIC concentrations (MIC = 64 μg/ml). The results of crystallization study showed that allicin inhibited pH rise and consequently turbidity and precipitation of ions in a dose-dependent manner. The results of catheter blockage study showed that allicin at sub-MIC concentrations (2, 4, 8 μg/ml) significantly increased the time for catheter blockage to occur to 61, 74 and 92 h respectively compared to allicin-free control (48 h). In a similar way, the results showed that allicin delayed the increase of SU pH level in bladder model in a dose-dependent manner compared to allicin-free control. The results also showed that following the increase of allicin concentration, Mg[2+] and Ca[2+] deposition in catheters were much lower compared to allicin-free control, further confirmed by direct observation of the catheters' eyehole and cross sections. We conclude that allicin prevents the formation of Proteus-induced urinary crystals and the blockage of catheters by delaying pH increase and lowering Mg[2+] and Ca[2+] deposition in a dose-dependent manner.}, }
@article {pmid30910829, year = {2019}, author = {Ibeh, CL and Yiu, AJ and Kanaras, YL and Paal, E and Birnbaumer, L and Jose, PA and Bandyopadhyay, BC}, title = {Evidence for a regulated Ca[2+] entry in proximal tubular cells and its implication in calcium stone formation.}, journal = {Journal of cell science}, volume = {132}, number = {9}, pages = {}, pmid = {30910829}, issn = {1477-9137}, support = {R01 DK102043/DK/NIDDK NIH HHS/United States ; R21 EB021483/EB/NIBIB NIH HHS/United States ; Z01 ES101684/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Epithelial Cells/metabolism ; Kidney Calculi/*etiology ; Kidney Tubules, Proximal/cytology/*metabolism ; LLC-PK1 Cells ; Loop of Henle/cytology/metabolism ; Mice ; Receptors, Calcium-Sensing/*metabolism ; Signal Transduction ; Swine ; TRPC Cation Channels/*metabolism ; }, abstract = {Calcium phosphate (CaP) crystals, which begin to form in the early segments of the loop of Henle (LOH), are known to act as precursors for calcium stone formation. The proximal tubule (PT), which is just upstream of the LOH and is a major site for Ca[2+] reabsorption, could be a regulator of such CaP crystal formation. However, PT Ca[2+] reabsorption is mostly described as being paracellular. Here, we show the existence of a regulated transcellular Ca[2+] entry pathway in luminal membrane PT cells induced by Ca[2+]-sensing receptor (CSR, also known as CASR)-mediated activation of transient receptor potential canonical 3 (TRPC3) channels. In support of this idea, we found that both CSR and TRPC3 are physically and functionally coupled at the luminal membrane of PT cells. More importantly, TRPC3-deficient mice presented with a deficiency in PT Ca[2+] entry/transport, elevated urinary [Ca[2+]], microcalcifications in LOH and urine microcrystals formations. Taken together, these data suggest that a signaling complex comprising CSR and TRPC3 exists in the PT and can mediate transcellular Ca[2+] transport, which could be critical in maintaining the PT luminal [Ca[2+]] to mitigate formation of the CaP crystals in LOH and subsequent formation of calcium stones.}, }
@article {pmid30838875, year = {2019}, author = {Curry, JN and Yu, ASL}, title = {Paracellular calcium transport in the proximal tubule and the formation of kidney stones.}, journal = {American journal of physiology. Renal physiology}, volume = {316}, number = {5}, pages = {F966-F969}, pmid = {30838875}, issn = {1522-1466}, support = {F30 DK109605/DK/NIDDK NIH HHS/United States ; P20 GM130423/GM/NIGMS NIH HHS/United States ; R01 DK115727/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Claudins/metabolism ; Humans ; Hypercalciuria/*complications/metabolism/physiopathology ; Ion Transport ; Kidney Calculi/*etiology/metabolism/physiopathology ; Kidney Tubules, Proximal/*metabolism/physiopathology ; Membrane Transport Proteins/*metabolism ; Nephrocalcinosis/*etiology/metabolism/physiopathology ; *Renal Reabsorption ; }, abstract = {The proximal tubule (PT) is responsible for the majority of calcium reabsorption by the kidney. Most PT calcium transport appears to be passive, although the molecular facilitators have not been well established. Emerging evidence supports a major role for PT calcium transport in idiopathic hypercalciuria and the development of kidney stones. This review will cover recent developments in our understanding of PT calcium transport and the role of the PT in kidney stone formation.}, }
@article {pmid30798331, year = {2019}, author = {Cairoli, E and Eller-Vainicher, C and Morlacchi, LC and Tarsia, P and Rossetti, V and Pappalettera, M and Arosio, M and Chiodini, I and Blasi, F}, title = {Bone involvement in young adults with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure.}, journal = {Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA}, volume = {30}, number = {6}, pages = {1255-1263}, pmid = {30798331}, issn = {1433-2965}, mesh = {Adult ; Bone Density/physiology ; Cross-Sectional Studies ; Cystic Fibrosis/blood/*complications/physiopathology ; Female ; Humans ; *Lung Transplantation ; Male ; Middle Aged ; Nephrolithiasis/etiology ; Osteoporosis/blood/*etiology/physiopathology ; Osteoporotic Fractures/blood/etiology/physiopathology ; Respiratory Insufficiency/blood/*etiology/physiopathology/surgery ; Vitamin D/analogs &amp; derivatives/blood ; Vitamin D Deficiency/blood/etiology/physiopathology ; Young Adult ; }, abstract = {UNLABELLED: Patients with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure have high prevalence of reduced bone mineral density and fragility fracture. Suboptimal 25-hydroxyvitamin D levels could significantly contribute to the development of cystic fibrosis-related bone disease.<br><br>INTRODUCTION: The assessment of the prevalence of cystic fibrosis-related bone disease (CFBD) and its associated risk factors in young adults with cystic fibrosis (CF) awaiting lung transplantation for end-stage respiratory failure.<br><br>METHODS: Clinical characteristics, bone mineral density (BMD), the parameters of calcium metabolism, including vitamin D (25OHVitD) levels, and the presence of fragility fractures were evaluated in 42 CF patients (24 females, age 34.0&#x2009;&#xb1;&#x2009;8.4&#xa0;years) consecutively referred as lung transplant candidates.<br><br>RESULTS: Mean 25OHVitD levels (54.9&#x2009;&#xb1;&#x2009;26.2&#xa0;nmol/L) were below the reference range and hypovitaminosis D (25OHVitD&#x2009;<&#x2009;75&#xa0;nmol/L) was found in 34 patients (81%) and daily calcium intakes (median 550&#xa0;mg/day) were lower than recommended. A BMD below the expected range for age (Z-score of -&#x2009;2.0 or lower) and at least one prevalent fragility fracture were found in 22 patients (52.4%) and 18 patients (45.2%), respectively. The coexistence of low BMD and the presence of fracture was observed in 13 patients (31.0%). In these patients, the prevalence of nephrolithiasis was higher than in the remaining ones (p&#x2009;=&#x2009;0.046). The presence of kidney stones was associated with a worse bone status and with severe vitamin D deficiency. In the whole sample, femoral BMD Z-scores were directly correlated with albumin-adjusted calcium (p&#x2009;<&#x2009;0.05) and 25OHVitD levels (p&#x2009;<&#x2009;0.01).<br><br>CONCLUSIONS: Despite the improvement of CF care, CFBD is still highly prevalent in young adults awaiting lung transplantation for end-stage CF. Suboptimal 25OHVitD levels could significantly contribute to the development of CFBD. The presence of nephrolithiasis could be an additional warning about the need for a careful evaluation of bone health in CF patients.}, }
@article {pmid30761807, year = {2018}, author = {Filippova, TV and Litvinova, MM and Rudenko, VI and Gadzhieva, ZK and Rapoport, LM and Kazilov, YB and Asanov, AY and Subbotina, TI and Khafizov, KF}, title = {[Genetic factors for monogenic forms of calcium urolithiasis].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {4}, pages = {154-160}, pmid = {30761807}, issn = {1728-2985}, mesh = {Calcium ; Humans ; *Urinary Calculi ; *Urolithiasis ; }, abstract = {The article presents pooled results of domestic and international studies investigating genetic aspects of urolithiasis associated with impaired calcium metabolism. The review highlights the importance of early and accurate diagnosis of hereditary diseases associated with kidney stone formation. Of more than 80 currently known monogenic forms of urolithiasis, the authors provide the list of the most significant forms. Using such molecular genetic methods as NGS (next generation sequencing) allows accurate detection of the genetic cause of the disease, develop an individual approach the patients management and timely prevention of the disease among the relatives of the proband.}, }
@article {pmid30696888, year = {2019}, author = {Gombedza, F and Evans, S and Shin, S and Awuah Boadi, E and Zhang, Q and Nie, Z and Bandyopadhyay, BC}, title = {Melamine promotes calcium crystal formation in three-dimensional microfluidic device.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {875}, pmid = {30696888}, issn = {2045-2322}, support = {R01 DK102043/DK/NIDDK NIH HHS/United States ; R21 EB021483/EB/NIBIB NIH HHS/United States ; }, mesh = {Calcium/metabolism ; Calcium Oxalate/chemistry/metabolism ; Calcium Phosphates/chemistry/metabolism ; Calcium, Dietary ; Cell Line ; Crystallization ; Humans ; Kidney/metabolism ; Kidney Calculi/*chemistry/metabolism ; Kidney Tubules, Proximal/chemistry/*metabolism ; Lab-On-A-Chip Devices ; Minerals ; Triazines/*chemistry ; }, abstract = {Melamine, which induces proximal tubular (PT) cell damage has a greater nephrotoxic effect when combined with cyanuric and uric acids; however, it is unknown whether such effect can stimulate calcium phosphate (CaP)/calcium oxalate (CaOx) stone formation. Here, we show that melamine acts as an inducer of CaP, CaOx and CaP + CaOx (mixed) crystal formations in a time and concentration-dependent manner by stabilizing those crystals and further co-aggregating with melamine. To explore the physiological relevance of such melamine-augmented calcium crystal formation, we used 2-dimensional (2D) and 3D microfluidic (MF) device, embedded with PT cells, which also resembled the effect of melamine-stimulated CaP, CaOx and mixed crystal formation. Significantly, addition of preformed CaP and/or CaOx crystal in the presence of melamine, further potentiated those crystal formations in 3D MFs, which helped the growth and aggregation of mixed crystals. Our data show that the mechanism of such predisposition of stone formation could be largely due to co-crystallization between melamine and CaP/CaOx and pronounced effect on induction of stone-forming pathway activation in 3D MF. Taken together, melamine-induced CaP and/or CaOx crystal formation ex-vivo will help us in understanding the larger role of melamine as an environmental toxicant in producing the pathology in similar cellular microenvironments.}, }
@article {pmid30680550, year = {2019}, author = {Pozdzik, A and Maalouf, N and Letavernier, E and Brocheriou, I and Body, JJ and Vervaet, B and Van Haute, C and Noels, J and Gadisseur, R and Castiglione, V and Cotton, F and Gambaro, G and Daudon, M and Sakhaee, K}, title = {Meeting report of the "Symposium on kidney stones and mineral metabolism: calcium kidney stones in 2017".}, journal = {Journal of nephrology}, volume = {32}, number = {5}, pages = {681-698}, pmid = {30680550}, issn = {1724-6059}, mesh = {Calcium/*metabolism ; Crystallization ; Decision Trees ; Humans ; Kidney Calculi/epidemiology/etiology/*metabolism/therapy ; Minerals/metabolism ; Nephrocalcinosis/genetics ; Nephrolithiasis/genetics ; }, abstract = {A symposium on kidney stones and mineral metabolism held on December 2017 in Brussels, Belgium was the first international multidisciplinary conference of the International Collaborative Network on Kidney Stones and Mineral Metabolism. This meeting addressed epidemiology, underlying pathophysiological mechanisms, genetics, pathological, as well as clinical and research topics. The participants included clinicians and recognized experts in the field from Europe and the United States interacted closely during the symposium which promoted a chance to explore new frontiers in the field of kidney stone disease. This manuscript summarizes some of the major highlights of the meeting.}, }
@article {pmid30673801, year = {2019}, author = {Oliveira, B and Unwin, R and Walsh, SB}, title = {Inherited proximal tubular disorders and nephrolithiasis.}, journal = {Urolithiasis}, volume = {47}, number = {1}, pages = {35-42}, pmid = {30673801}, issn = {2194-7236}, mesh = {Amino Acid Transport Systems/*genetics/metabolism ; Calcium/metabolism ; Humans ; Kidney Calculi/*genetics/physiopathology ; Kidney Tubules, Proximal/pathology/*physiopathology ; Phosphate Transport Proteins/*genetics/metabolism ; Phosphates/metabolism ; Renal Elimination/*genetics ; }, abstract = {The proximal tubule is responsible for reclaiming water, phosphates and amino acids from the tubular filtrate. There are genetic defects in both phosphate and amino acid transporters leading to nephrolithiasis. This review also explores genetic defects in regulators of phosphate and calcium transport in this nephron segment that lead to stone formation.}, }
@article {pmid30531474, year = {2019}, author = {Rimer, JD and Sakhaee, K and Maalouf, NM}, title = {Citrate therapy for calcium phosphate stones.}, journal = {Current opinion in nephrology and hypertension}, volume = {28}, number = {2}, pages = {130-139}, doi = {10.1097/MNH.0000000000000474}, pmid = {30531474}, issn = {1473-6543}, mesh = {Calcium Chelating Agents/*therapeutic use ; Calcium Phosphates/analysis/*urine ; Citric Acid/chemistry/*therapeutic use/urine ; Crystallization ; Humans ; Kidney Calculi/chemistry/*prevention &amp; control/urine ; Secondary Prevention ; }, abstract = {PURPOSE OF REVIEW: Calcium phosphate (CaP) stones represent an increasingly encountered form of recurrent nephrolithiasis, but current prophylactic medical regimens are suboptimal. Although hypocitraturia is a well-described risk factor for CaP stones, strategies that enhance citrate excretion have not consistently been effective at reducing CaP saturation and stone recurrence. This review summarizes the role of citrate therapy in CaP nephrolithiasis.<br><br>RECENT FINDINGS: Citrate in urine inhibits CaP stone formation through multiple mechanisms, including the formation of soluble citrate-calcium complexes, and inhibition of CaP nucleation, crystal growth and crystal aggregation. Recent in-vitro studies demonstrate that citrate delays CaP crystal growth through distinct inhibitory mechanisms that depend on supersaturation and citrate concentration. The impact of pharmacological provision of citrate on CaP saturation depends on the accompanying cation: Potassium citrate imparts a significant alkali load that enhances citraturia and reduces calciuria, but could worsen urine pH elevation. Conversely, citric acid administration results in minimal citraturia and alteration in CaP saturation.<br><br>SUMMARY: Citrate, starting at very low urinary concentrations, can significantly retard CaP crystal growth in vitro through diverse mechanisms. Clinically, the net impact on CaP stone formation of providing an alkali load during pharmacological delivery of citrate into the urinary environment remains to be determined.}, }
@article {pmid30505182, year = {2018}, author = {Idrees, N and Tabassum, B and Abd Allah, EF and Hashem, A and Sarah, R and Hashim, M}, title = {Groundwater contamination with cadmium concentrations in some West U.P. Regions, India.}, journal = {Saudi journal of biological sciences}, volume = {25}, number = {7}, pages = {1365-1368}, pmid = {30505182}, issn = {1319-562X}, abstract = {Water is considered a vital resource because it is necessary for all aspects of human and ecosystem survival. However, due to natural processes and anthropogenic activities, various pollutants have been added to the ground water system. Among these, heavy metals are some of the most serious pollutants. Cd, a toxic heavy metal used in Ni-Cd batteries, the colouration of plastic and various discarded electronic products released into the water system causes serious health issues. The chronic exposure to Cd produces a wide variety of acute and chronic effects in humans. Cd accumulates in the human body, especially in the kidneys, resulting in kidney damage (renal tubular damage), which is a critical health effect. Other effects of Cd exposure are disturbances in calcium metabolism, hypercalciuria and the formation of kidney stones. High exposure to Cd can lead to lung cancer and prostate cancer; hence, poor quality water that may result in Cd toxicity has become a global concern. Thus, the aim of this study is to determine the concentration of Cd in underground water sources in western U.P. regions. Water samples were acidified to 1% with nitric acid and then stored in double-capped polyethylene bottles for further analysis by an atomic absorption spectrophotometer. After comparing the data to the WHO (2011) permissible limit, the study revealed that the concentration of Cd was higher than the regulatory threshold; therefore, the underground water system is seriously affected by Cd toxicity.}, }
@article {pmid30515733, year = {2019}, author = {Tavasoli, S and Taheri, M and Taheri, F and Basiri, A and Bagheri Amiri, F}, title = {Evaluating the associations between urinary excretion of magnesium and that of other components in calcium stone-forming patients.}, journal = {International urology and nephrology}, volume = {51}, number = {2}, pages = {279-284}, pmid = {30515733}, issn = {1573-2584}, mesh = {Adult ; *Calcium/metabolism/urine ; Correlation of Data ; Creatinine/analysis ; Cross-Sectional Studies ; Female ; Humans ; Hydrogen-Ion Concentration ; Iran/epidemiology ; *Kidney/metabolism/physiopathology ; *Kidney Calculi/chemistry/epidemiology/metabolism/urine ; *Magnesium/metabolism/urine ; Male ; Middle Aged ; Oxalates/metabolism/urine ; *Renal Elimination ; Retrospective Studies ; Urinalysis/methods ; }, abstract = {PURPOSE: Magnesium plays numerous vital roles in human's body. It is known as a protective factor in stone formation by binding to oxalate in the intestinal and urinary system, and decreasing its absorption and crystallization, respectively. Due to controversies about the association between the 24-h urine magnesium and other urine metabolites in different studies, this study was designed to find a clear answer to this question.<br><br>METHODS: In this retrospective cross-sectional study, data from 24-h urinalysis of the calcium stone-forming (CSF) patients were assessed. The correlation between 24-h urine (24-U) magnesium to creatinine ratio (Mg/Cr) with other 24-U metabolites to creatinine ratio was assessed, using Spearman correlation test. The association between 24-U magnesium and 24-U oxalate was also studied in a multivariate logistic regression model.<br><br>RESULTS: Among 965 patients, the level of Mg/Cr showed a direct association with all other 24-U metabolite to Cr ratio (p-value&#x2009;<&#x2009;0.001 for all analyses). The result of multivariate regression analysis showed that the higher quartile of 24-U oxalate (>&#x2009;47&#xa0;mg/24&#xa0;h) increased the odds of 24-U magnesium more than 75&#xa0;mg/24&#xa0;h (data median) (OR 1.89, 95% CI 1.14-3.13) comparing with the lower quartile of 24-U oxalate (&#x2264;&#x2009;26&#xa0;mg/24&#xa0;h).<br><br>CONCLUSIONS: In a routine dietary habit, since rich sources of magnesium contain a high amount of oxalate at the same time, it is not surprising that magnesium level in 24-h urinalysis showed a direct association with 24-h urine oxalate.}, }
@article {pmid30460527, year = {2019}, author = {Faller, N and Dhayat, NA and Fuster, DG}, title = {Nephrolithiasis secondary to inherited defects in the thick ascending loop of henle and connecting tubules.}, journal = {Urolithiasis}, volume = {47}, number = {1}, pages = {43-56}, pmid = {30460527}, issn = {2194-7236}, mesh = {Calcium/metabolism ; Disease Progression ; Genome-Wide Association Study ; Humans ; Ion Channels/*genetics/metabolism ; Loop of Henle/*metabolism/pathology ; Mutation ; Nephrocalcinosis/etiology/pathology ; Nephrolithiasis/*etiology/pathology ; Renal Elimination/genetics ; Renal Insufficiency, Chronic/*genetics/pathology ; Renal Reabsorption/genetics ; Renal Tubular Transport, Inborn Errors/complications/*genetics/pathology ; }, abstract = {Twin and genealogy studies suggest a strong genetic component of nephrolithiasis. Likewise, urinary traits associated with renal stone formation were found to be highly heritable, even after adjustment for demographic, anthropometric and dietary covariates. Recent high-throughput sequencing projects of phenotypically well-defined cohorts of stone formers and large genome-wide association studies led to the discovery of many new genes associated with kidney stones. The spectrum ranges from infrequent but highly penetrant variants (mutations) causing mendelian forms of nephrolithiasis (monogenic traits) to common but phenotypically mild variants associated with nephrolithiasis (polygenic traits). About two-thirds of the genes currently known to be associated with nephrolithiasis code for membrane proteins or enzymes involved in renal tubular transport. The thick ascending limb of Henle and connecting tubules are of paramount importance for renal water and electrolyte handling, urinary concentration and maintenance of acid-base homeostasis. In most instances, pathogenic variants in genes involved in thick ascending limb of Henle and connecting tubule function result in phenotypically severe disease, frequently accompanied by nephrocalcinosis with progressive CKD and to a variable degree by nephrolithiasis. The aim of this article is to review the current knowledge on kidney stone disease associated with inherited defects in the thick ascending loop of Henle and the connecting tubules. We also highlight recent advances in the field of kidney stone genetics that have implications beyond rare disease, offering new insights into the most common type of kidney stone disease, i.e., idiopathic calcium stone disease.}, }
@article {pmid30446806, year = {2019}, author = {Vezzoli, G and Macrina, L and Magni, G and Arcidiacono, T}, title = {Calcium-sensing receptor: evidence and hypothesis for its role in nephrolithiasis.}, journal = {Urolithiasis}, volume = {47}, number = {1}, pages = {23-33}, pmid = {30446806}, issn = {2194-7236}, mesh = {5' Untranslated Regions/genetics ; Calcium/*metabolism ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Introns/genetics ; Kidney Tubules/*metabolism ; Nephrolithiasis/*genetics/metabolism ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic/genetics ; Receptors, Calcium-Sensing/*genetics/metabolism ; Renal Elimination/genetics ; Renal Reabsorption/genetics ; }, abstract = {Calcium-sensing receptor (CaSR) is a plasma-membrane G protein-coupled receptor activated by extracellular calcium and expressed in kidney tubular cells. It inhibits calcium reabsorption in the ascending limb and distal convoluted tubule when stimulated by the increase of serum calcium levels; therefore, these tubular segments are enabled by CaSR to play a substantial role in the regulation of serum calcium levels. In addition, CaSR increases water and proton excretion in the collecting duct and promotes phosphate reabsorption and citrate excretion in the proximal tubule. These CaSR activities form a network in which they are integrated to protect the kidney against the negative effects of high calcium concentrations and calcium precipitates in urine. Therefore, the CaSR gene has been considered as a candidate to explain calcium nephrolithiasis. Epidemiological studies observed that calcium nephrolithiasis was associated with polymorphisms of the CaSR gene regulatory region, rs6776158, located within the promoter-1, rs1501899 located in the intron 1, and rs7652589 in the 5'-untranslated region. These polymorphisms were found to reduce the transcriptional activity of promoter-1. Activating rs1042636 polymorphism located in exon 7 was associated with calcium nephrolithiasis and hypercalciuria. Genetic polymorphisms decreasing CaSR expression could predispose individuals to stones because they may impair CaSR protective effects against precipitation of calcium phosphate and oxalate. Activating polymorphisms rs1042636 could predispose to calcium stones by increasing calcium excretion. These findings suggest that CaSR may play a complex role in lithogenesis through different pathways having different relevance under different clinical conditions.}, }
@article {pmid30407920, year = {2019}, author = {David, K and Moyson, C and Vanderschueren, D and Decallonne, B}, title = {Long-term complications in patients with chronic hypoparathyroidism: a cross-sectional study.}, journal = {European journal of endocrinology}, volume = {180}, number = {1}, pages = {71-78}, doi = {10.1530/EJE-18-0580}, pmid = {30407920}, issn = {1479-683X}, mesh = {Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; Hypercalciuria/*etiology ; Hypoparathyroidism/*complications/drug therapy ; Kidney Calculi/*etiology ; Male ; Middle Aged ; Quality of Life ; Retrospective Studies ; Seizures/*etiology ; Vitamin D/therapeutic use ; }, abstract = {Objective Chronic hypoparathyroidism and its treatment may lead to symptoms and complications affecting quality of life. We determined complications in chronic hypoparathyroid patients. Design Retrospective cross-sectional study of patients with chronic hypoparathyroidism treated with active vitamin D supplements in a tertiary care centre during the year 2015. Primary outcome parameters were history of kidney stones and seizures and presence of renal and cerebral calcifications on imaging. Secondary outcome parameters were current symptoms of paraesthesia/cramps, hospitalization due to hyper/hypocalcaemia and hypercalciuria. Subjects One hundred and seventy patients were included - 143 (84%) with post-surgical hypoparathyroidism (PSHP), 16 (9%) with non-surgical hypoparathyroidism (NSHP) and 11 (7%) with pseudo-hypoparathyroidism (PHP). Results History of kidney stones and seizures was present in 15 and 9% of patients, respectively. Renal and cerebral imaging was performed in 51 and 26% of the patients, with 22 and 25% of these patients having renal and cerebral calcifications respectively. Both history of seizures and cerebral calcifications were significantly more in NSHP and PHP than in PSHP patients. No association was observed between seizures and cerebral calcifications. Cramps/paraesthesia were present in 16%, and hospitalization related to hypocalcaemia was reported in 5% of the patients. Calciuria was screened in 47% at the time of consultation, and in 76% of the patients during the past 5 years. In 36% of these patients, calciuria was increased. Conclusions Patients with chronic hypoparathyroidism frequently develop ectopic calcifications. Non-surgical patients suffer more from seizures and cerebral calcifications than patients that developed hypoparathyroidism post surgery. There is a need for increased screening of long-term complications, according to the guidelines.}, }
@article {pmid30325822, year = {2018}, author = {Raynor, WY and Al-Zaghal, A and Werner, TJ and Høilund-Carlsen, PF and Alavi, A}, title = {18F-NaF PET/CT in Prostatic Calculi.}, journal = {Clinical nuclear medicine}, volume = {43}, number = {12}, pages = {e484-e485}, doi = {10.1097/RLU.0000000000002317}, pmid = {30325822}, issn = {1536-0229}, mesh = {Calcinosis/*diagnostic imaging ; Humans ; Male ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Prostatic Diseases/*diagnostic imaging ; Radiopharmaceuticals ; Sodium Fluoride ; }, abstract = {Primary prostatic calculi commonly present asymptomatically in men over the age of 50 years. Individual calculi form when the secretory tube is blocked by inflammation, prostatic secretions, or corpora amylacea. Although small prostatic calculi have been described as a component of normal aging, increased prevalence of calculi has been associated with benign prostatic hyperplasia and prostatitis. We are presenting prostatic calcification in a 69-year-old man as incidentally detected on F-NaF PET/CT. Although previous publications have reported F-NaF uptake portraying calcification in soft tissue, these findings demonstrate a new domain in which to assess calcium metabolism using F-NaF PET/CT.}, }
@article {pmid30213590, year = {2018}, author = {Tanaka, H and Imasato, M and Yamazaki, Y and Matsumoto, K and Kunimoto, K and Delpierre, J and Meyer, K and Zerial, M and Kitamura, N and Watanabe, M and Tamura, A and Tsukita, S}, title = {Claudin-3 regulates bile canalicular paracellular barrier and cholesterol gallstone core formation in mice.}, journal = {Journal of hepatology}, volume = {69}, number = {6}, pages = {1308-1316}, doi = {10.1016/j.jhep.2018.08.025}, pmid = {30213590}, issn = {1600-0641}, mesh = {Aging/physiology ; Animals ; Aquaporins/metabolism ; Bile Canaliculi/*metabolism ; Calcium/metabolism ; Calcium Phosphates/metabolism ; Cell Membrane Permeability/*physiology ; Cholesterol/*metabolism ; Claudin-3/genetics/*metabolism ; Claudins/genetics/metabolism ; Female ; Gallstones/*metabolism ; Gene Knockout Techniques ; Liver/metabolism ; Male ; Mice ; Mice, Knockout ; Phosphorus/metabolism ; Tight Junctions/metabolism ; }, abstract = {BACKGROUND &amp; AIMS: Most cholesterol gallstones have a core consisting of inorganic and/or organic calcium salts, although the mechanisms of core formation are poorly understood. We examined whether the paracellular permeability of ions at hepatic tight junctions is involved in the core formation of cholesterol gallstones, with particular interest in the role of phosphate ion, a common food additive and preservative.<br><br>METHODS: We focused on claudin-3 (Cldn3), a paracellular barrier-forming tight junction protein whose expression in mouse liver decreases with age. Since Cldn3-knockout mice exhibited gallstone diseases, we used them to assess the causal relationship between paracellular phosphate ion permeability and the core formation of cholesterol gallstones.<br><br>RESULTS: In the liver of Cldn3-knockout mice, the paracellular phosphate ion permeability through hepatic tight junctions was significantly increased, resulting in calcium phosphate core formation. Cholesterol overdose caused cholesterol gallstone disease in these mice.<br><br>CONCLUSION: We revealed that in the hepatobiliary system, Cldn3 functions as a paracellular barrier for phosphate ions, to help maintain biliary ion homeostasis. We provide in vivo evidence that elevated phosphate ion concentrations play a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease under cholesterol overdose.<br><br>LAY SUMMARY: Herein, we reveal a new mechanism for cholesterol gallstone formation, in which increased paracellular phosphate ion permeability across hepatobiliary epithelia causes calcium phosphate core formation and cholesterol gallstones. Thus, altered phosphate ion metabolism under cholesterol overdose plays a major role in the lifestyle- and age-related risks of developing cholesterol gallstone disease.}, }
@article {pmid30175942, year = {2019}, author = {Wang, L and Holmes, RP and Peng, JB}, title = {Modeling the structural and dynamical changes of the epithelial calcium channel TRPV5 caused by the A563T variation based on the structure of TRPV6.}, journal = {Journal of biomolecular structure &amp; dynamics}, volume = {37}, number = {13}, pages = {3506-3512}, pmid = {30175942}, issn = {1538-0254}, support = {R01 DK104924/DK/NIDDK NIH HHS/United States ; }, mesh = {Binding Sites ; Calcium/*metabolism ; Calcium Channels/*chemistry/genetics/*metabolism ; Humans ; Models, Molecular ; *Molecular Dynamics Simulation ; *Polymorphism, Single Nucleotide ; Protein Binding ; Protein Conformation ; TRPV Cation Channels/*chemistry/genetics/*metabolism ; }, abstract = {TRPV5, transient receptor potential cation channel vanilloid subfamily member 5, is an epithelial Ca[2+] channel that plays a key role in the active Ca[2+] reabsorption process in the kidney. A single nucleotide polymorphism (SNP) rs4252499 in the TRPV5 gene results in an A563T variation in the sixth transmembrane (TM) domain of TRPV5. Our previous study indicated that this variation increases the Ca[2+] transport function of TRPV5. To understand the molecular mechanism, a model of TRPV5 was established based on the newly deposited structure of TRPV6 that has 83.1% amino acid identity with TRPV5 in the modeled region. Computational simulations were performed to study the structural and dynamical differences between the TRPV5 variants with A563 and T563. Consistent with the TRPV1-based simulation, the results indicate that the A563T variation increases the contacts between residues 563 and V540, which is one residue away from the key residue D542 in the Ca[2+]-selective filter. The variation enhanced the stability of the secondary structure of the pore region, decreased the fluctuation of residues around residue 563, and reduced correlated and anti-correlated motion between monomers. Furthermore, the variation increases the pore radius at the selective filter. These findings were confirmed using simulations based on the recently determined structure of rabbit TRPV5. The simulation results provide an explanation for the observation of enhanced Ca[2+] influx in TRPV5 caused by the A563T variation. The A563T variation is an interesting example of how a residue distant from the Ca[2+]-selective filter influences the Ca[2+] transport function of the TRPV5 channel. Communicated by Ramaswamy H. Sarma.}, }
@article {pmid30082495, year = {2018}, author = {Ali, SN and Dayarathna, TK and Ali, AN and Osumah, T and Ahmed, M and Cooper, TT and Power, NE and Zhang, D and Kim, D and Kim, R and St Amant, A and Hou, J and Tailly, T and Yang, J and Luyt, L and Spagnuolo, PA and Burton, JP and Razvi, H and Leong, HS}, title = {Drosophila melanogaster as a function-based high-throughput screening model for antinephrolithiasis agents in kidney stone patients.}, journal = {Disease models &amp; mechanisms}, volume = {11}, number = {11}, pages = {}, pmid = {30082495}, issn = {1754-8411}, mesh = {Animals ; Arbutin/analysis/pharmacology/therapeutic use ; Birefringence ; Calcium/metabolism ; Calcium Oxalate ; Diphosphonates ; Drosophila melanogaster/*metabolism ; Drug Evaluation, Preclinical ; Feces ; HEK293 Cells ; High-Throughput Screening Assays/*methods ; Humans ; Ions ; Kidney Calculi/*drug therapy ; *Models, Biological ; Nanoparticles ; }, abstract = {Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper.}, }
@article {pmid29961155, year = {2018}, author = {Dos Santos, PMC and Amaral, D and Tararthuch, AL and Fernandez, R}, title = {Calcium-sensing receptor (CaSR) modulates vacuolar H[+]-ATPase activity in a cell model of proximal tubule.}, journal = {Clinical and experimental nephrology}, volume = {22}, number = {6}, pages = {1258-1265}, pmid = {29961155}, issn = {1437-7799}, mesh = {Animals ; Calcium/metabolism ; Cells, Cultured ; Hydrogen-Ion Concentration ; Kidney Tubules, Proximal/*metabolism ; Neomycin/pharmacology ; Opossums ; Receptors, Calcium-Sensing/*physiology ; Type C Phospholipases/metabolism ; Vacuolar Proton-Translocating ATPases/*metabolism ; }, abstract = {BACKGROUND: The calcium-sensing receptor (CaSR) is localized in the apical membrane of proximal tubules in close proximity to the transporters responsible for proton secretion. Therefore, the aim of the present study was to analyze the effects of CaSR stimulation on the biochemical activity of the vacuolar H[+]-ATPase in a cellular model of proximal tubule cells, OKP cells.<br><br>METHODS: Biochemical activity of H[+]-ATPase was performed using cell homogenates, and the inorganic phosphate released was determined by a colorimetric method. Changes in cytosolic ionized calcium [Ca[2+]]i were also determined using Fluo-4.<br><br>RESULTS: A significant increase of vacuolar H[+]-ATPase activity was observed when the CaSR was stimulated with agonists such as Gd[3+] (300&#xa0;&#xb5;M) and neomycin (200&#xa0;&#xb5;M). This activity was also stimulated in a dose-dependent fashion by changes in extracellular Ca[2+] (Ca[2+]o) between 10[-4] and 2&#xa0;mM. Gd[3+] and neomycin produced a sustained rise of [Ca[2+]]i, an effect that disappears when extracellular calcium was removed in the presence of 0.1&#xa0;&#xb5;M thapsigargin. Inhibition of phospholipase C (PLC) activity with U73122 (5&#x2009;&#xd7;&#x2009;10[-8]&#xa0;M) reduced the increase in [Ca[2+]]i induced by neomycin.<br><br>CONCLUSION: CaSR stimulation induces an increase in the vacuolar H[+]-ATPase activity of OKP cells, an effect that involves an increase in [Ca[2+]]i and require phospholipase C activity. The consequent decrease in intratubular pH could lead to increase ionization of luminal calcium, potentially enhancing its reabsorption in distal tubule segments and reducing the formation of calcium phosphate stones.}, }
@article {pmid29935264, year = {2018}, author = {Wang, Q and Hu, H and Dirie, NI and Lu, Y and Zhang, J and Cui, L and Qin, B and Wang, Y and Zhu, J and Xun, Y and Zhu, Y and Wu, Y and Wang, S}, title = {High Concentration of Calcium Promotes Mineralization in NRK-52E Cells Via Inhibiting the Expression of Matrix Gla Protein.}, journal = {Urology}, volume = {119}, number = {}, pages = {161.e1-161.e7}, doi = {10.1016/j.urology.2018.06.006}, pmid = {29935264}, issn = {1527-9995}, mesh = {Animals ; Calcinosis/etiology ; Calcium/*metabolism ; Calcium-Binding Proteins/*antagonists &amp; inhibitors/*biosynthesis ; Cells, Cultured ; Extracellular Matrix Proteins/*antagonists &amp; inhibitors/*biosynthesis ; Kidney Diseases/*etiology ; Rats ; }, abstract = {OBJECTIVE: To address whether matrix Gla protein (MGP) can inhibit mineralization in normal rat kidney tubular cells (NRK-52E) under high concentration of calcium.<br><br>MATERIALS AND METHODS: NRK-52E cells were treated with high concentration of calcium. The viability and apoptosis of cells were detected by cell counting kit-8 and flow cytology, respectively. Real-time-polymerase chain, Western blotting, and immunofluorescence analysis were conducted to detect the expression of MGP. Cells were transfected with plasmid-MGP or siRNA-MGP for up- or down-regulation of the expression of MGP, respectively. Rat recombinant MGP was also used as supplementation of exogenous MGP. Alizarin red staining was conducted to detect the adherent and deposition of calcium salt.<br><br>RESULTS: High concentration of calcium suppressed MGP expression in NRK-52E cells. There was significant mineralization when NRK-52E cells were treated with high concentration of calcium. Supplementation with exogenous rat recombinant MGP and overexpression of endogenous MGP both decreased the adherent and deposition of calcium salt to NRK-52E cells, while silence of MGP showed reverse results.<br><br>CONCLUSION: MGP plays an inhibitory role in the stone formation. However, high concentration of calcium significantly inhibits the expression of MGP and then promotes mineralization in NRK-52E cells.}, }
@article {pmid29926935, year = {2018}, author = {Johnson, E and Vu, L and Matarese, LE}, title = {Bacteria, Bones, and Stones: Managing Complications of Short Bowel Syndrome.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {33}, number = {4}, pages = {454-466}, doi = {10.1002/ncp.10113}, pmid = {29926935}, issn = {1941-2452}, mesh = {Bacteria/*growth &amp; development ; Bone Density ; Bone and Bones/*metabolism ; Calcium/*metabolism ; Colon/metabolism ; Humans ; Intestinal Mucosa/metabolism/microbiology ; *Intestine, Small/metabolism/microbiology ; Kidney/metabolism/pathology ; Kidney Calculi/*etiology/metabolism ; Osteoporosis/etiology ; Oxalates/metabolism ; Short Bowel Syndrome/*complications ; }, abstract = {Short bowel syndrome (SBS) occurs in patients who have had extensive resection. The primary physiologic consequence is malabsorption, resulting in fluid and electrolyte abnormalities and malnutrition. Nutrient digestion, absorption, and assimilation may also be diminished by disturbances in the production of bile acids and digestive enzymes. Small bowel dilation, dysmotility, loss of ileocecal valve, and anatomical changes combined with acid suppression and antimotility drugs increase the risk of small intestinal bacterial overgrowth, further contributing to malabsorption. Metabolic changes that occur in SBS due to loss of colonic regulation of gastric and small bowel function can also lead to depletion of calcium, magnesium, and vitamin D, resulting in demineralization of bone and the eventual development of bone disease. Persistent inflammation, steroid use, parenteral nutrition, chronic metabolic acidosis, and renal insufficiency may exacerbate the problem and contribute to the development of osteoporosis. Multiple factors increase the risk of nephrolithiasis in SBS. In the setting of fat malabsorption, increased free fatty acids are available to bind to calcium, resulting in an increased concentration of unbound oxalate, which is readily absorbed across the colonic mucosa where it travels to the kidney. In addition, there is an increase in colonic permeability to oxalate stemming from the effects of unabsorbed bile salts. The risk of nephrolithiasis is compounded by volume depletion, metabolic acidosis, and hypomagnesemia, resulting in a decrease in renal perfusion, urine output, pH, and citrate excretion. This review examines the causes and treatments of small intestinal bacterial overgrowth, bone demineralization, and nephrolithiasis in SBS.}, }
@article {pmid29901287, year = {2018}, author = {Demidko, LS and Rudenko, VI and Grigoryan, VA and Demidko, YL and Enikeev, ME and Inoyatov, ZS and Amosova, MV}, title = {[Characteristic features of urinary calcium excretion and osteoporosis risk factors in patients with urolithiasis].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {2}, pages = {5-8}, pmid = {29901287}, issn = {1728-2985}, mesh = {Adult ; Calcium/*urine ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis/*urine ; Risk Factors ; Urolithiasis/*urine ; }, abstract = {RELEVANCE: The prevalence of urolithiasis and osteoporosis (OP) indicates that these diseases may be found concurrently in the same patient. The detection of risk factors for OP and disorders of calcium metabolism in patients with urolithiasis is of interest in the context of primary stone formation and metaphylaxis.<br><br>AIM: To identify risk factors for osteoporosis and disorders of calcium metabolism in patients with urolithiasis.<br><br>MATERIALS AND METHODS: Osteoporosis risk factors were studied in 45 urolithiasis patients undergoing surgical treatment. Patients were asked to fill out the osteoporosis risk factor questionnaire, and urinary calcium excretion was measured in 24-h collections.<br><br>RESULTS: Risk factors for osteoporosis were detected in 20 (44.4%) urolithiasis patients. Patients with osteoporosis risk factors identified by the questionnaire were statistically significantly older (p=0.032). Osteoporosis risk factors were found in 20% of patients with newly diagnosed urolithiasis and 24.4% of patients with recurrent urolithiasis. The study patients showed increased urinary calcium excretion and decreased diuresis. The negative correlation between urinary calcium excretion and 24-h diuresis was greater in patients who had than in those who did not have osteoporosis.<br><br>CONCLUSION: An increase in urinary calcium excretion and a decrease in diuresis can be a predisposing factor for the recurrence of urolithiasis. In patients with risk factors for osteoporosis, it can provide a rationale for administering drugs aimed at preventing stone formation (thiazide diuretics).}, }
@article {pmid29807024, year = {2018}, author = {Fowler, ED and Drinkhill, MJ and Norman, R and Pervolaraki, E and Stones, R and Steer, E and Benoist, D and Steele, DS and Calaghan, SC and White, E}, title = {Beta1-adrenoceptor antagonist, metoprolol attenuates cardiac myocyte Ca[2+] handling dysfunction in rats with pulmonary artery hypertension.}, journal = {Journal of molecular and cellular cardiology}, volume = {120}, number = {}, pages = {74-83}, pmid = {29807024}, issn = {1095-8584}, support = {FS/13/8/29974/BHF_/British Heart Foundation/United Kingdom ; PG/13/3/29924/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Adrenergic beta-1 Receptor Antagonists/administration &amp; dosage/*therapeutic use ; Analysis of Variance ; Animals ; Calcium/*metabolism ; Disease Models, Animal ; Echocardiography ; Electrocardiography ; Heart Failure/metabolism ; Hypertension, Pulmonary/diagnostic imaging/*drug therapy ; Hypertrophy, Right Ventricular/drug therapy ; Male ; Metoprolol/administration &amp; dosage/*therapeutic use ; Myocytes, Cardiac/*metabolism ; Pulmonary Artery/*physiopathology ; Rats ; Rats, Wistar ; Stroke Volume/drug effects ; Ventricular Dysfunction, Right/diagnostic imaging/*drug therapy ; }, abstract = {Right heart failure is the major cause of death in Pulmonary Artery Hypertension (PAH) patients but is not a current, specific therapeutic target. Pre-clinical studies have shown that adrenoceptor blockade can improve cardiac function but the mechanisms of action within right ventricular (RV) myocytes are unknown. We tested whether the β1-adrenoceptor blocker metoprolol could improve RV myocyte function in an animal model of PAH, by attenuating adverse excitation-contraction coupling remodeling. PAH with RV failure was induced in rats by monocrotaline injection. When PAH was established, animals were given 10 mg/kg/day metoprolol (MCT + BB) or vehicle (MCT). The median time to the onset of heart failure signs was delayed from 23 days (MCT), to 31 days (MCT + BB). At 23 ± 1 days post-injection, MCT + BB showed improved in vivo cardiac function, measured by echocardiography. RV hypertrophy was reduced despite persistent elevated afterload. RV myocyte contractility during field stimulation was improved at higher pacing frequencies in MCT + BB. Preserved t-tubule structure, more uniform evoked Ca[2+] release, increased SERCA2a expression and faster ventricular repolarization (measured in vivo by telemetry) may account for the improved contractile function. Sarcoplasmic reticulum Ca[2+] overload was prevented in MCT + BB myocytes resulting in fewer spontaneous Ca[2+] waves, with a lower pro-arrhythmic potential. Our novel finding of attenuation of defects in excitation contraction coupling by β1-adrenoceptor blockade with delays in the onset of HF, identifies the RV as a promising therapeutic target in PAH. Moreover, our data suggest existing therapies for left ventricular failure may also be beneficial in PAH induced RV failure.}, }
@article {pmid29796583, year = {2018}, author = {Tessaro, CZW and Ramos, CI and Heilberg, IP}, title = {Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in calcium stone formers.}, journal = {Jornal brasileiro de nefrologia : 'orgao oficial de Sociedades Brasileira e Latino-Americana de Nefrologia}, volume = {40}, number = {1}, pages = {35-43}, pmid = {29796583}, issn = {2175-8239}, mesh = {Calcium/analysis/*metabolism ; *Diet ; Female ; Humans ; Kidney Calculi/chemistry/complications/*metabolism/urine ; Male ; Middle Aged ; *Nutritional Status ; Obesity/complications/metabolism/urine ; Overweight/complications/*metabolism/urine ; Retrospective Studies ; Uric Acid/*urine ; }, abstract = {INTRODUCTION: Obesity and Metabolic Syndrome (MS) are associated with low urinary pH and represent risk factors for nephrolithiasis, especially composed by uric acid. Acidogenic diets may also contribute to a reduction of urinary pH. Propensity for calcium oxalate precipitation has been shown to be higher with increasing features of the MS.<br><br>OBJECTIVE: A retrospective evaluation of anthropometric and body composition parameters, MS criteria and the dietary patterns of overweight and obese calcium stone formers and their impact upon urinary pH and other lithogenic parameters was performed.<br><br>METHODS: Data regarding anthropometry, body composition, serum and urinary parameters and 3-days dietary records were obtained from medical records of 102(34M/68F) calcium stone formers.<br><br>RESULTS: A negative correlation was found between urinary pH, waist circumference and serum uric acid levels (males). The endogenous production of organic acids (OA) was positively correlated with triglycerides levels and number of features of MS (males), and with glucose, uric acid and triglycerides serum levels, and number of features of MS (females). No significant correlations were detected between Net Acid Excretion (NAE) or Potential Renal Acid Load of the diet with any of the assessed parameters. A multivariate analysis showed a negative association between OA and urinary pH.<br><br>CONCLUSION: The endogenous production of OA and not an acidogenic diet were found to be independently predictive factors for lower urinary pH levels in calcium stone formers. Hypercalciuric and/or hyperuricosuric patients presented higher OA levels and lower levels of urinary pH.}, }
@article {pmid29792045, year = {2019}, author = {Viljoen, A and Chaudhry, R and Bycroft, J}, title = {Renal stones.}, journal = {Annals of clinical biochemistry}, volume = {56}, number = {1}, pages = {15-27}, doi = {10.1177/0004563218781672}, pmid = {29792045}, issn = {1758-1001}, mesh = {Calcium/metabolism ; Humans ; *Kidney Calculi/epidemiology/physiopathology/therapy ; Risk Factors ; Uric Acid/metabolism ; }, abstract = {Renal stone disease is a worldwide problem which carries significant morbidity. It frequently requires specialist urology intervention. Patients with recurrent disease and those at high risk require specialist investigations and review. Certain cases benefit from medical and surgical intervention. In this review, we discuss the pathophysiology, risk assessment, specialist investigations and various interventions, their rationale and evidence base. This review aims to provide an update of the previous publication in 2001 in this journal on this topic.}, }
@article {pmid29782491, year = {2018}, author = {Berens, P and Freeman, J and Deneux, T and Chenkov, N and McColgan, T and Speiser, A and Macke, JH and Turaga, SC and Mineault, P and Rupprecht, P and Gerhard, S and Friedrich, RW and Friedrich, J and Paninski, L and Pachitariu, M and Harris, KD and Bolte, B and Machado, TA and Ringach, D and Stone, J and Rogerson, LE and Sofroniew, NJ and Reimer, J and Froudarakis, E and Euler, T and Román Rosón, M and Theis, L and Tolias, AS and Bethge, M}, title = {Community-based benchmarking improves spike rate inference from two-photon calcium imaging data.}, journal = {PLoS computational biology}, volume = {14}, number = {5}, pages = {e1006157}, pmid = {29782491}, issn = {1553-7358}, support = {108726/WT_/Wellcome Trust/United Kingdom ; R21 EY027592/EY/NEI NIH HHS/United States ; U19 NS104649/NS/NINDS NIH HHS/United States ; R01 EB022913/EB/NIBIB NIH HHS/United States ; R01 EB022915/EB/NIBIB NIH HHS/United States ; R01 EY012816/EY/NEI NIH HHS/United States ; U19 NS107613/NS/NINDS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 EY018322/EY/NEI NIH HHS/United States ; DP1 EY023176/EY/NEI NIH HHS/United States ; }, mesh = {Action Potentials/*physiology ; Algorithms ; Animals ; Calcium/chemistry/*metabolism/physiology ; Computational Biology/*methods ; Databases, Factual ; Mice ; *Models, Neurological ; Molecular Imaging ; Optical Imaging ; Retina/cytology ; Retinal Neurons/cytology/metabolism ; }, abstract = {In recent years, two-photon calcium imaging has become a standard tool to probe the function of neural circuits and to study computations in neuronal populations. However, the acquired signal is only an indirect measurement of neural activity due to the comparatively slow dynamics of fluorescent calcium indicators. Different algorithms for estimating spike rates from noisy calcium measurements have been proposed in the past, but it is an open question how far performance can be improved. Here, we report the results of the spikefinder challenge, launched to catalyze the development of new spike rate inference algorithms through crowd-sourcing. We present ten of the submitted algorithms which show improved performance compared to previously evaluated methods. Interestingly, the top-performing algorithms are based on a wide range of principles from deep neural networks to generative models, yet provide highly correlated estimates of the neural activity. The competition shows that benchmark challenges can drive algorithmic developments in neuroscience.}, }
@article {pmid29782346, year = {2018}, author = {Plain, A and Alexander, RT}, title = {Claudins and nephrolithiasis.}, journal = {Current opinion in nephrology and hypertension}, volume = {27}, number = {4}, pages = {268-276}, doi = {10.1097/MNH.0000000000000426}, pmid = {29782346}, issn = {1473-6543}, support = {MOP 136891//CIHR/Canada ; }, mesh = {Animals ; Calcium/*metabolism ; Cell Membrane Permeability ; Claudins/*metabolism ; Humans ; Hypercalciuria/metabolism ; Ion Transport ; Kidney Tubules/*metabolism ; Nephrocalcinosis/metabolism ; Nephrolithiasis/*metabolism/physiopathology ; Tight Junctions/metabolism ; }, abstract = {PURPOSE OF REVIEW: The greatest risk factor for kidney stone formation is increased urinary calcium excretion. Most filtered calcium is reabsorbed from the proximal tubule and the thick ascending limb (TAL) of Henle's loop via a paracellular pathway. Claudins are tight junction proteins that confer the permeability properties of an epithelium. We review the contribution of renal claudins to nephron calcium permeability and how perturbations in these pathways cause alterations in tubular calcium transport, hypercalciuria, nephrocalcinosis, or nephrolithiasis.<br><br>RECENT FINDINGS: Claudin-16 and Claudin-19 form a complex with claudin-3 enabling divalent cation permeability in the TAL. Claudin-14 interacts with claudin-16 to attenuate calcium permeability through this pore. Intronic mutations in claudin-14 increase expression causing hypercalciuria and kidney stones. A different type of TAL tight junction pore is composed of claudin-10b, which does not preferentially permeate calcium. Deletion of claudin-10b results in increased expression of the claudin-16/claudin-19 complex expressed in the medullary TAL and nephrocalcinosis.<br><br>SUMMARY: Alterations to claudins expressed in the TAL tight junction greatly affects calcium homeostasis as highlighted by point mutations in claudin-16 or claudin-19 causing FHHNC or gain of function mutations in claudin-14 causing kidney stones.}, }
@article {pmid29638127, year = {2018}, author = {Zhang, H and Mine, Y}, title = {Is Calcium-Sensing Receptor a New Molecular Target toward Improving Gastrointestinal Health?.}, journal = {Journal of agricultural and food chemistry}, volume = {66}, number = {16}, pages = {3995-3997}, doi = {10.1021/acs.jafc.8b01150}, pmid = {29638127}, issn = {1520-5118}, mesh = {Animals ; Calcium/metabolism ; Gastrointestinal Tract/drug effects/*metabolism ; Homeostasis ; Humans ; Peptides/pharmacology ; Receptors, Calcium-Sensing/agonists/antagonists &amp; inhibitors/genetics/*metabolism ; }, }
@article {pmid29587817, year = {2018}, author = {Sakaue, Y and Takenaka, S and Ohsumi, T and Domon, H and Terao, Y and Noiri, Y}, title = {The effect of chlorhexidine on dental calculus formation: an in vitro study.}, journal = {BMC oral health}, volume = {18}, number = {1}, pages = {52}, pmid = {29587817}, issn = {1472-6831}, mesh = {Biofilms/drug effects ; Calcium/metabolism ; Chlorhexidine/*analogs &amp; derivatives/therapeutic use ; Dental Calculus/metabolism/*prevention &amp; control/ultrastructure ; Electron Probe Microanalysis ; Humans ; In Vitro Techniques ; Microscopy, Electron, Scanning ; Phosphates/metabolism ; Saliva/drug effects ; Spectrophotometry, Atomic ; }, abstract = {BACKGROUND: Chlorhexidine gluconate (CHG) has been proven to be effective in preventing and controlling biofilm formation. At the same time, an increase in calculus formation is known as one of considerable side effects. The purpose of this study was to investigate whether mineral deposition preceding a calculus formation would occur at an early stage after the use of CHG using an in vitro saliva-related biofilm model.<br><br>METHODS: Biofilms were developed on the MBEC&#x2122; device in brain heart infusion (BHI) broth containing 0.5% sucrose at 37&#xa0;&#xb0;C for 3 days under anaerobic conditions. Biofilms were periodically exposed to 1&#xa0;min applications of 0.12% CHG every 12&#xa0;h and incubated for up to 2 days in BHI containing a calcifying solution. Calcium and phosphate in the biofilm were measured using atomic absorption spectrophotometry and a phosphate assay kit, respectively. Morphological structure was observed using a scanning electron microscope (SEM), and chemical composition was analyzed with an electron probe microanalyzer (EPMA).<br><br>RESULTS: The concentrations of Ca and Pi following a single exposure to CHG increased significantly compared with the control. Repeatedly exposing biofilms to CHG dose-dependently increased Ca deposition, and the amount of Ca was five times as much as that of the control. Pi levels in CHG-treated biofilms were significantly higher than those from the control group (p&#xa0;<&#xa0;0.05); however, the influence of the number of exposures was limited. Analyses using an SEM and EPMA showed many clusters containing calcium and phosphate complexes in CHG-treated biofilms. Upon composition analysis of the clusters, calcium was detected at a greater concentration than phosphate.<br><br>CONCLUSIONS: Findings suggested that CHG may promote mineral uptake into the biofilm soon after its use. It is necessary to disrupt the biofilm prior to the start of a CHG mouthwash in order to reduce the side effects associated with this procedure. The management of patients is also important.}, }
@article {pmid29562593, year = {2018}, author = {Letavernier, E and Daudon, M}, title = {Vitamin D, Hypercalciuria and Kidney Stones.}, journal = {Nutrients}, volume = {10}, number = {3}, pages = {}, pmid = {29562593}, issn = {2072-6643}, mesh = {Animals ; Biomarkers/blood ; Dietary Supplements/*adverse effects ; Humans ; Hypercalciuria/*chemically induced/diagnosis/epidemiology/urine ; Kidney Calculi/*chemically induced/diagnosis/epidemiology/metabolism ; Prognosis ; Risk Factors ; Vitamin D/*adverse effects/*analogs &amp; derivatives/blood ; Vitamin D Deficiency/blood/diagnosis/*drug therapy/epidemiology ; }, abstract = {The estimated lifetime risk of nephrolithiasis is growing nowadays, and the formation of kidney stones is frequently promoted by hypercalciuria. Vitamin D, and especially its active metabolite calcitriol, increase digestive calcium absorption-as urinary calcium excretion is directly correlated with digestive calcium absorption, vitamin D metabolites could theoretically increase calciuria and promote urinary stone formation. Nevertheless, there was, until recently, low evidence that 25-hydroxyvitamin D serum levels would be correlated with kidney stone formation, even if high calcitriol concentrations are frequently observed in hypercalciuric stone formers. Low 25-hydroxyvitamin D serum levels have been associated with a broad spectrum of diseases, leading to a huge increase in vitamin D prescription in the general population. In parallel, an increased frequency of kidney stone episodes has been observed in prospective studies evaluating vitamin D alone or in association with calcium supplements, and epidemiological studies have identified an association between high 25-hydroxyvitamin D serum levels and kidney stone formation in some groups of patients. Moreover, urinary calcium excretion has been shown to increase in response to vitamin D supplements, at least in some groups of kidney stone formers. It seems likely that predisposed individuals may develop hypercalciuria and kidney stones in response to vitamin D supplements.}, }
@article {pmid29559506, year = {2018}, author = {Devarajan, A}, title = {Cross-talk between renal lithogenesis and atherosclerosis: an unveiled link between kidney stone formation and cardiovascular diseases.}, journal = {Clinical science (London, England : 1979)}, volume = {132}, number = {6}, pages = {615-626}, doi = {10.1042/CS20171574}, pmid = {29559506}, issn = {1470-8736}, mesh = {Animals ; Arteries/*metabolism/pathology ; Atherosclerosis/epidemiology/*metabolism/pathology ; Calcium/metabolism ; Crystallization ; Humans ; Kidney/*metabolism/pathology ; Kidney Calculi/epidemiology/*metabolism/pathology ; Lipids/blood ; Oxalates/metabolism ; Oxidation-Reduction ; Plaque, Atherosclerotic ; Prevalence ; Prognosis ; Proteins/metabolism ; Risk Factors ; Uric Acid/blood ; }, abstract = {The prevalence of kidney stones and cardiovascular diseases (CVDs) are increasing throughout the world. Both diseases are chronic and characterized by accumulation of oxidized proteins and lipids in the renal tissue and arterial wall, respectively. Emerging studies have revealed a positive association between nephrolithiasis and CVDs. Based on preclinical and clinical evidences, this review discusses: (i) stone forming risk factors, crystal nucleation, aggregation, injury-induced crystal retention, and stone formation, (ii) CVD risk factors such as dyslipidemia, perturbation of gut microbiome, obesity, free radical-induced lipoprotein oxidation, and retention in the arterial wall, subsequent foam cell formation, and atherosclerosis, (iii) mechanism by which stone forming risk factors such as oxalate, calcium, uric acid, and infection contribute toward CVDs, and (iv) how CVD risk factors, such as cholesterol, phospholipids, and uric acid, contribute to kidney stone formation are described.}, }
@article {pmid29383416, year = {2018}, author = {Walker, RW and Zhang, S and Coleman-Barnett, JA and Hamm, LL and Hering-Smith, KS}, title = {Calcium receptor signaling and citrate transport.}, journal = {Urolithiasis}, volume = {46}, number = {5}, pages = {409-418}, pmid = {29383416}, issn = {2194-7236}, support = {R01 DK095879/DK/NIDDK NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biological Transport ; Calcium/*metabolism ; Cells, Cultured ; Citric Acid/*metabolism ; Dicarboxylic Acids/metabolism ; Kidney Tubules, Distal/cytology/*metabolism ; Kidney Tubules, Proximal/cytology/*metabolism ; Opossums ; Receptors, Calcium-Sensing/*metabolism ; Renal Elimination ; }, abstract = {The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium. We previously demonstrated a novel apical calcium-sensitive dicarboxylate transport system in OK proximal tubule cells. This calcium-sensitive process has the potential to modulate the amount of citrate available to complex increased urinary calcium. Using isotope labeled succinate uptake in OK cells along with various pharmacologic tools we examined whether the CaSR alters apical dicarboxylate transport and through which signal transduction pathways this occurs. Our results indicate that in the proximal tubule CaSR adjusts apical dicarboxylate transport, and does so via a CaSR → Gq → PKC signaling pathway. Thus, the CaSR may decrease the propensity for stone formation via actions in both proximal and distal nephron segments.}, }
@article {pmid29357414, year = {2018}, author = {van der Wijst, J and Tutakhel, OAZ and Bos, C and Danser, AHJ and Hoorn, EJ and Hoenderop, JGJ and Bindels, RJM}, title = {Effects of a high-sodium/low-potassium diet on renal calcium, magnesium, and phosphate handling.}, journal = {American journal of physiology. Renal physiology}, volume = {315}, number = {1}, pages = {F110-F122}, doi = {10.1152/ajprenal.00379.2017}, pmid = {29357414}, issn = {1522-1466}, mesh = {Animal Feed ; Animals ; Calcium/blood/*metabolism/urine ; Gene Expression Regulation ; Homeostasis ; Kidney Tubules, Distal/*metabolism ; Magnesium/blood/*metabolism/urine ; Male ; Membrane Transport Proteins/genetics/metabolism ; Mice, Inbred C57BL ; Phosphates/blood/*metabolism/urine ; Potassium, Dietary/*administration &amp; dosage/metabolism ; *Renal Reabsorption ; Sodium Chloride, Dietary/*administration &amp; dosage/metabolism ; Time Factors ; }, abstract = {The distal convoluted tubule (DCT) of the kidney plays an important role in blood pressure regulation by modulating Na[+] reabsorption via the Na[+]-Cl[-] cotransporter (NCC). A diet containing high salt (NaCl) and low K[+] activates NCC, thereby causing Na[+] retention and a rise in blood pressure. Since high blood pressure, hypertension, is associated with changes in serum calcium (Ca[2+]) and magnesium (Mg[2+]) levels, we hypothesized that dietary Na[+] and K[+] intake affects Ca[2+] and Mg[2+] transport in the DCT. Therefore, the present study aimed to investigate the effect of a high-Na[+]/low-K[+] diet on renal Ca[2+] and Mg[2+] handling. Mice were divided in four groups and fed a normal-Na[+]/normal-K[+], normal-Na[+]/low-K[+], high-Na[+]/normal-K[+], or high-Na[+]/low-K[+] diet for 4 days. Serum and urine were collected for electrolyte and hormone analysis. Gene and protein expression of electrolyte transporters were assessed in kidney and intestine by qPCR and immunoblotting. Whereas Mg[2+] homeostasis was not affected, the mice had elevated urinary Ca[2+] and phosphate (Pi) excretion upon high Na[+] intake, as well as significantly lower serum Ca[2+] levels in the high-Na[+]/low-K[+] group. Alterations in the gene and protein expression of players involved in Ca[2+] and Pi transport indicate that reabsorption in the proximal tubular and TAL is affected, while inducing a compensatory response in the DCT. These effects may contribute to the negative health impact of a high-salt diet, including kidney stone formation, chronic kidney disease, and loss of bone mineral density.}, }
@article {pmid29135159, year = {2017}, author = {Kamalov, AA and Okhobotov, DA and Nizov, AN}, title = {[The role of the Randalls plaques in the pathogenesis of recurrent urolitasis].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {5}, pages = {145-148}, doi = {10.18565/urology.2017.5.145-148}, pmid = {29135159}, issn = {1728-2985}, mesh = {Calcium/*metabolism ; Humans ; Urinary Calculi/*metabolism/*ultrastructure ; Urothelium/*metabolism/*ultrastructure ; }, abstract = {The aim of the work was to present current concept of the pathogenesis of urolithiasis. Treatment and prevention of this disease a challenging issue. The article presents basic information about Randalls plaques that are described as calcium salt deposits on the surface of the transitional cell epithelium. The cause of Randalls plaques was the subject of many studies and is still not completely clear. To date, we can state that the deposit formation starts in the pelvicalyceal system and is directly linked to recurrent urolithiasis. The discovery of Randall plaques in the 1940s transformed the conception of stone formation, but there are even more questions about the pathogenesis of urolithiasis. In that respect, we consider it important to analyze the studies on Randalls plaques.}, }
@article {pmid29135157, year = {2017}, author = {Egshatyan, LV and Mokrysheva, NG}, title = {[Calciuria as a metabolic marker for various conditions and diseases].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {5}, pages = {132-138}, doi = {10.18565/urology.2017.5.132-138}, pmid = {29135157}, issn = {1728-2985}, mesh = {Bone Resorption/*urine ; Calcium/*urine ; Humans ; Hypercalcemia/*urine ; *Intestinal Absorption ; Kidney Diseases/*urine ; }, abstract = {The article analyzes the literature on the features of human calcium homeostasis. The authors describe the etiopathogenetic role of calcitropic hormones, the plasma and urine acid-base status, various ions, lifestyle and nutrition and other factors contributing to hypercalciuria due to increased intestinal absorption, bone resorption, impairment of tubular calcium reabsorption, etc. They discuss the role of calciuria as a factor in forming urinary calculi and present their own observations.}, }
@article {pmid29126251, year = {2018}, author = {Bergsland, KJ and Coe, FL and Parks, JH and Asplin, JR and Worcester, EM}, title = {Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {33}, number = {5}, pages = {759-770}, pmid = {29126251}, issn = {1460-2385}, support = {P01 DK056788/DK/NIDDK NIH HHS/United States ; }, mesh = {Biomarkers/*analysis ; Calcium/metabolism ; Cohort Studies ; Female ; Glomerular Filtration Rate ; Humans ; Hypophosphatemia/*etiology/metabolism/pathology ; Kidney Calculi/*complications ; Male ; Middle Aged ; Organic Anion Transporters/*metabolism ; Organic Cation Transport Proteins/*metabolism ; *PDZ Domains ; Phosphates/metabolism ; Phosphoproteins/*metabolism ; Sodium-Hydrogen Exchanger 3/*metabolism ; Sodium-Hydrogen Exchangers/*metabolism ; Uric Acid/metabolism ; }, abstract = {BACKGROUND: Hypophosphatemia (HYP) is common among calcium stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP.<br><br>METHODS: To test this idea, we analyzed two large but separate sets of 24-h urine samples and paired serums of 2700 SFs from the University of Chicago and 11&#x2009;073 SFs from Litholink, a national laboratory. Patients were divided into quintiles based on serum phosphate.<br><br>RESULTS: Males were more common in the lowest phosphate tiles in both datasets. Phosphate excretion did not vary across the quintiles, excluding diet as a cause of HYP. Tubule maximum (Tm) phosphate per unit glomerular filtration rate decreased and fractional excretion increased with decreasing phosphate quintiles, indicating reduced tubule phosphate reabsorption was responsible for HYP. Urine pH and serum chloride increased with decreasing serum phosphate, suggesting a coordinate change in NHE3 activity. Serum uric acid and Tm uric acid decreased significantly with decreasing serum phosphate, while uric acid excretion did not vary. Conclusion. HYP in SFs results from decreased tubule phosphate reabsorption and, being associated with related changes in other proximal tubule transporters, may arise from alterations in or signaling to PDZ-containing proteins.}, }
@article {pmid29101657, year = {2017}, author = {Whisner, CM and Weaver, CM}, title = {Prebiotics and Bone.}, journal = {Advances in experimental medicine and biology}, volume = {1033}, number = {}, pages = {201-224}, doi = {10.1007/978-3-319-66653-2_10}, pmid = {29101657}, issn = {0065-2598}, mesh = {Animals ; Bone Density/drug effects ; Bone Diseases/physiopathology/prevention &amp; control ; Bone Remodeling/drug effects/physiology ; Bone and Bones/*drug effects/physiology ; Calcium/metabolism/pharmacokinetics ; Fractures, Bone/physiopathology/prevention &amp; control ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Intestinal Absorption/drug effects ; Prebiotics/*administration &amp; dosage ; Signal Transduction/*drug effects ; }, abstract = {Recent advancements in food science have resulted in the extraction and synthesis of novel dietary fibers or prebiotics. Subsequently, great interest has emerged in developing strategies to improve metabolic conditions like osteoporosis by modulating the intestinal microbiome with fiber. Prebiotics have been shown to increase calcium absorption in the lower gut of both animals and humans as well as improve measures of bone mineral density and strength in rodent models. Fewer data are available in humans, but data from growing children and postmenopausal women suggest that prebiotics have both short- and long-term effects that beneficially affect bone turnover and mineral accretion in the skeleton. Currently, the exact mechanism by which these products elicit their effects on bone is poorly understood, but emerging data suggest that the gut microbiota may be involved in one or more direct and indirect pathways. The most well-accepted mechanism is through microbial fermentation of prebiotics which results in the production of short-chain fatty acids and a concomitant decrease in pH which increases the bioavailability of calcium in the colon. While other mechanisms may be eliciting a prebiotic effect on bone, the current data suggest that novel dietary fibers may be an affordable and effective method of maximizing mineral accretion in growing children and preventing bone loss in later years when osteoporosis is a greater risk. This chapter will discuss the dynamic role of prebiotics in bone health by discussing the current state of the art, addressing gaps in knowledge and their role in public health.}, }
@article {pmid29085969, year = {2018}, author = {Ergon, EY and Akil, &#x130;O and Taneli, F and Oran, A and Ozyurt, BC}, title = {Etiologic risk factors and vitamin D receptor gene polymorphisms in under one-year-old infants with urolithiasis.}, journal = {Urolithiasis}, volume = {46}, number = {4}, pages = {349-356}, pmid = {29085969}, issn = {2194-7236}, mesh = {Calcium/metabolism/urine ; Case-Control Studies ; Diet Surveys ; Dietary Supplements/*adverse effects ; Female ; Gene Frequency ; *Genetic Predisposition to Disease ; Humans ; Hypercalciuria/*epidemiology/*genetics/urine ; Incidence ; Infant ; Infant Formula ; Infant, Newborn ; Male ; Polymorphism, Restriction Fragment Length ; Receptors, Calcitriol/*genetics ; Risk Factors ; Turkey/epidemiology ; Urolithiasis/*epidemiology/*genetics/urine ; Vitamin D/administration &amp; dosage/*adverse effects ; }, abstract = {The incidence of urinary tract stones in infancy has been increasing in Turkey. Risk factors and vitamin D receptor (VDR) gene polymorphisms were investigated in infants aged < 1 year who had stones. Forty infants with urinary tract stones and 80 infants without stones, aged < 1 year were enrolled in this study. Detailed surveys were taken of all infants, metabolic parameters and ApaI and FokI VDR gene polymorphisms were investigated. Infants with stones tended to be more commonly fed formula and multivitamins (vitamins A, C, D) (p < 0.05). Positive family history came into prominence in the stony group (p < 0.05). There were no significant differences in ApaI and FokI VDR gene polymorphisms between the groups with stones and the control groups. However, CA genotype of ApaI polymorphism was associated with family history and C allele of ApaI was related with family history and hypercalciuria (p < 0.05). Hypercalciuria emerged as an underlying metabolic abnormality in the etiology of stones, and was observed at a rate of 38%. Infants who are given formula and multivitamins for vitamin D supplementation are at increased risk for the formation of urinary tract stones. VDR gene polymorphisms cause the formation of urinary tract stones and affect calcium (Ca) metabolism.}, }
@article {pmid28923463, year = {2018}, author = {Bilezikian, JP and Bandeira, L and Khan, A and Cusano, NE}, title = {Hyperparathyroidism.}, journal = {Lancet (London, England)}, volume = {391}, number = {10116}, pages = {168-178}, doi = {10.1016/S0140-6736(17)31430-7}, pmid = {28923463}, issn = {1474-547X}, mesh = {Humans ; Hyperparathyroidism, Primary/*diagnosis/epidemiology/*therapy ; }, abstract = {Primary hyperparathyroidism is a common endocrine disorder of calcium metabolism characterised by hypercalcaemia and elevated or inappropriately normal concentrations of parathyroid hormone. Almost always, primary hyperparathyroidism is due to a benign overgrowth of parathyroid tissue either as a single gland (80% of cases) or as a multiple gland disorder (15-20% of cases). Primary hyperparathyroidism is generally discovered when asymptomatic but the disease always has the potential to become symptomatic, resulting in bone loss and kidney stones. In countries where biochemical screening tests are not common, symptomatic primary hyperparathyroidism tends to predominate. Another variant of primary hyperparathyroidism has been described in which the serum calcium concentration is within normal range but parathyroid hormone is elevated in the absence of any obvious cause. Primary hyperparathyroidism can be cured by removal of the parathyroid gland or glands but identification of patients who are best advised to have surgery requires consideration of the guidelines that are regularly updated. Recommendations for patients who do not undergo parathyroid surgery include monitoring of serum calcium concentrations and bone density.}, }
@article {pmid28847730, year = {2017}, author = {Wang, L and Holmes, RP and Peng, JB}, title = {The L530R variation associated with recurrent kidney stones impairs the structure and function of TRPV5.}, journal = {Biochemical and biophysical research communications}, volume = {492}, number = {3}, pages = {362-367}, pmid = {28847730}, issn = {1090-2104}, support = {R01 DK072154/DK/NIDDK NIH HHS/United States ; R01 DK104924/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism ; Genetic Variation/*genetics ; Humans ; Kidney Calculi/*metabolism ; Models, Molecular ; Oocytes/metabolism ; TRPV Cation Channels/chemistry/*genetics/*metabolism ; Xenopus ; }, abstract = {TRPV5 is a Ca[2+]-selective channel that plays a key role in the reabsorption of Ca[2+] ions in the kidney. Recently, a rare L530R variation (rs757494578) of TRPV5 was found to be associated with recurrent kidney stones in a founder population. However, it was unclear to what extent this variation alters the structure and function of TRPV5. To evaluate the function and expression of the TRPV5 variant, Ca[2+] uptake in Xenopus oocytes and western blot analysis were performed. The L530R variation abolished the Ca[2+] uptake activity of TRPV5 in Xenopus oocytes. The variant protein was expressed with drastic reduction in complex glycosylation. To assess the structural effects of this L530R variation, TRPV5 was modeled based on the crystal structure of TRPV6 and molecular dynamics simulations were carried out. Simulation results showed that the L530R variation disrupts the hydrophobic interaction between L530 and L502, damaging the secondary structure of transmembrane domain 5. The variation also alters its interaction with membrane lipid molecules. Compared to the electroneutral L530, the positively charged R530 residue shifts the surface electrostatic potential towards positive. R530 is attracted to the negatively charged phosphate group rather than the hydrophobic carbon atoms of membrane lipids. This shifts the pore helix where R530 is located and the D542 residue in the Ca[2+]-selective filter towards the surface of the membrane. These alterations may lead to misfolding of TRPV5, reduction in translocation of the channel to the plasma membrane and/or impaired Ca[2+] transport function of the channel, and ultimately disrupt TRPV5-mediated Ca[2+] reabsorption.}, }
@article {pmid28776078, year = {2018}, author = {Zeng, T and Duan, X and Zhu, W and Liu, Y and Wu, W and Zeng, G}, title = {SaRNA-mediated activation of TRPV5 reduces renal calcium oxalate deposition in rat via decreasing urinary calcium excretion.}, journal = {Urolithiasis}, volume = {46}, number = {3}, pages = {271-278}, pmid = {28776078}, issn = {2194-7236}, mesh = {Animals ; Calcium/metabolism/urine ; Calcium Channels/*genetics ; Calcium Oxalate/*chemistry/urine ; Disease Models, Animal ; Ethylene Glycol/toxicity ; Humans ; Hypercalciuria/*genetics/metabolism/urine ; Kidney/metabolism ; Kidney Calculi/chemically induced/*genetics/metabolism/urine ; Male ; Promoter Regions, Genetic ; RNA, Double-Stranded/administration &amp; dosage/*genetics ; Rats ; Rats, Sprague-Dawley ; Renal Reabsorption/genetics ; TRPV Cation Channels/*genetics ; Transcriptional Activation/genetics ; }, abstract = {Hypercalciuria is a main risk factor for kidney stone formation. TRPV5 is the gatekeeper protein for mediating calcium transport and reabsorption in the kidney. In the present study, we tested the effect of TRPV5 activation with small activating RNA (saRNA), which could induce gene expression by targeting the promoter of the gene, on ethylene glycol (EG)-induced calcium oxalate (CaOx) crystals formation in rat kidney. Five pairs of RNA activation sequences targeting the promoter of rat TRPV5 were designed and synthesized. The synthesized saRNA with the strongest activating effect was selected, and transcellular calcium transportation was tested by Fura-2 analysis. Subsequently, Sprague-Dawley rats were equally divided into three groups and fed with water, 1% EG for 28 days after injecting the negative control saRNA, 1% EG for 28 days after injecting the selected TRPV5-saRNA, respectively. The CaOx crystal formation and the 24-h urine components were assessed. In vitro study, saRNA ds-320 could significantly activate the expression of TRPV5 and transcellular calcium transportation. In vivo study, after 28 days treatment of EG, rats pre-infected with saRNA ds-320 had lower urinary calcium excretion and renal CaOx crystals formation as compared to that pre-infected with negative control saRNA. Activation of TRVP5 with saRNA ds-320 could inhibit EG-induced calcium oxalate crystals formation via promoting urine calcium reabsorption and decreasing urine calcium excretion in rats.}, }
@article {pmid28720371, year = {2017}, author = {Taguchi, K and Yasui, T and Milliner, DS and Hoppe, B and Chi, T}, title = {Genetic Risk Factors for Idiopathic Urolithiasis: A Systematic Review of the Literature and Causal Network Analysis.}, journal = {European urology focus}, volume = {3}, number = {1}, pages = {72-81}, doi = {10.1016/j.euf.2017.04.010}, pmid = {28720371}, issn = {2405-4569}, support = {P20 DK100863/DK/NIDDK NIH HHS/United States ; R21 DK109433/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Genome-Wide Association Study ; Humans ; Inflammation/genetics ; Oxidative Stress/genetics ; Phosphates/*metabolism ; Polymorphism, Single Nucleotide ; Risk Factors ; Urinary Calculi/chemistry ; Urolithiasis/*genetics ; }, abstract = {CONTEXT: Urolithiasis has a high prevalence and recurrence rate. Prevention is key to patient management, but risk stratification is challenging. In particular, genetic predisposition for urinary stones is not fully understood.<br><br>OBJECTIVE: To review current evidence of potential causative genes for idiopathic urolithiasis and map their relationships to one another. This evidence is essential for future establishment of molecular targeted therapy.<br><br>EVIDENCE ACQUISITION: A systematic literature review from 2007 to 2017 was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. The search was restricted to human studies conducted as either case-control or genome-wide association studies, and published in English. We also performed a causal network analysis of candidate genes gained from the systematic review using Ingenuity Pathway Analysis (IPA).<br><br>EVIDENCE SYNTHESIS: During the systematic screening of literature, 30 papers were selected for the review. A total of 20 genes with 42 polymorphisms/variants were found to be associated with urolithiasis risk. Their functional roles were mainly categorized as stone matrix, calcium and phosphate regulation, urinary concentration and constitution, and inflammation/oxidative stress. IPA network analysis revealed that these genes connected via signaling pathways and a proinflammatory/oxidative environment.<br><br>CONCLUSIONS: This systematic review provides an updated gene list and novel causal networks for idiopathic urolithiasis risk. Although some genes such as SPP1, CASR, VDR, CLDN14, and SLC34A1 were identified by several studies and recognized by prior reviews, further investigation elucidating their roles in stone formation will be essential for future studies.<br><br>PATIENT SUMMARY: In this review, we summarized recent literature regarding genes responsible for kidney stone risk. Based on a detailed review of 30 articles and computational network analysis, we concluded that disorder of mineral regulation with local inflammation in the kidney may cause kidney stone disease.}, }
@article {pmid28643676, year = {2017}, author = {Spivacow, FR and Palumbo, C}, title = {[Asymptomatic primary hyperparathyroidism in women].}, journal = {Medicina}, volume = {77}, number = {3}, pages = {196-200}, pmid = {28643676}, issn = {0025-7680}, mesh = {Aged ; Aged, 80 and over ; *Asymptomatic Diseases ; Biomarkers/metabolism ; Bone Diseases, Metabolic/*diagnosis/metabolism ; Calcium/metabolism ; Diagnosis, Differential ; Female ; Humans ; Hypercalcemia/*diagnosis/metabolism ; Hyperparathyroidism, Primary/*diagnosis/metabolism ; Male ; Middle Aged ; Osteoporosis/*diagnosis/metabolism ; Parathyroid Hormone/metabolism ; Prospective Studies ; }, abstract = {Primary hyperparathyroidism may have different characteristics. One is the asymptomatic form. This is a mild variant of hypercalcemic hyperparathyroidism, characterized by a calcemia not greater than 1 mg/dl above the upper limit of the method, a high intact parathyroid hormone (iPTH), absence of renal stones, renal function impairement, and osteoporosis, less than 50 years of age, and less than 400 mg/day calciuria. It is not a surgical entity, but its evolution may require it. Twenty-four postmenopausal women, all older than 50 years, with a diagnosis of asymptomatic hyperparathyroidism, were studied. Clinical manifestations, densitometric changes, biochemical parameters and bone remodeling were analyzed and the results were compared with the classic and normocalcemic variants of the disease. Diagnostic criteria were established and observed that only 2 (8.3%) of patients, during a follow up of 44 ± 12 months, had need for a parathyroidectomy. In conclusion, the asymptomatic primary hyperparathyroidism is a benign disorder, of periodic clinical follow-up, which rarely may require surgery.}, }
@article {pmid28624518, year = {2017}, author = {Sadaf, H and Raza, SI and Hassan, SW}, title = {Role of gut microbiota against calcium oxalate.}, journal = {Microbial pathogenesis}, volume = {109}, number = {}, pages = {287-291}, doi = {10.1016/j.micpath.2017.06.009}, pmid = {28624518}, issn = {1096-1208}, mesh = {Calcium/metabolism ; Calcium Oxalate/*metabolism/urine ; Calcium Phosphates/metabolism ; Diet ; Dietary Supplements ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Kidney Calculi/prevention &amp; control ; Lactobacillus/metabolism ; Nephrolithiasis/prevention &amp; control ; Oxalates/metabolism ; Oxalobacter formigenes/metabolism ; Probiotics/therapeutic use ; }, abstract = {Nephrolithiasis is a condition marked by the presence or formation of stones in kidneys. Several factors contribute to kidney stones development such as environmental conditions, type of dietary intake, gender and gastrointestinal flora. Most of the kidney stones are composed of calcium phosphate and calcium oxalate, which enter in to the body through diet. Both sources of oxalates become dangerous when normal flora of gastrointestinal tract is disturbed. Oxalobacter and Lactobacillus species exist symbiotically in the human gut and prevent stone formation by altering some biochemical pathways through production of specific enzymes which help in the degradation of oxalate salts. Both Oxalobacter and Lactobacillus have potential probiotic characteristics for the prevention of kidney stone formation and this avenue should be further explored.}, }
@article {pmid28623397, year = {2018}, author = {Rodgers, AL and Jappie-Mahomed, D and van Jaarsveld, PJ}, title = {Different effects of γ-linolenic acid (GLA) supplementation on plasma and red blood cell phospholipid fatty acid composition and calcium oxalate kidney stone risk factors in healthy subjects from two race groups with different risk profiles pose questions about the GLA-arachidonic acid-oxaluria metabolic pathway: pilot study.}, journal = {Urolithiasis}, volume = {46}, number = {2}, pages = {137-147}, pmid = {28623397}, issn = {2194-7236}, mesh = {Adult ; Arachidonic Acid/biosynthesis/blood ; Biomarkers/blood/urine ; Dietary Supplements ; Erythrocytes/metabolism ; Fatty Acids/blood/metabolism ; Healthy Volunteers ; Humans ; Hyperoxaluria/blood/ethnology/*metabolism/urine ; Linoleic Acids/blood/metabolism ; Male ; Metabolic Networks and Pathways/*drug effects ; Nephrolithiasis/blood/ethnology/*metabolism/urine ; Phospholipids/*blood/metabolism ; Pilot Projects ; Risk Factors ; Young Adult ; gamma-Linolenic Acid/blood/metabolism/pharmacology/*therapeutic use ; }, abstract = {Fatty acid (FA) composition of phospholipids in plasma and red blood cells (RBC) can influence calciuria, oxaluria and renal stone formation. In this regard, the ratio of arachidonic acid (AA) and its precursor linoleic acid (LA) appears to be important. Administration of γ-linolenic acid (GLA) has been shown to increase the concentration of dihomo-gamma linoleic acid (DGLA) relative to AA indicating that it may attenuate biosynthesis of the latter. Such effects have not been investigated in race groups having difference stone occurrence rates. Black (B) and white (W) healthy males ingested capsules containing linoleic acid (LA) and GLA, for 30 days. Plasma and RBC total phospholipid (TPL) FA profiles, serum and 24 h urine biomarkers of hypercalciuria and urinary stone risk factors were determined on days 0 and 30. Data were tested for statistical significance using GraphPadInstat version 3.02. Concentration and percentage content of DGLA in plasma TPL increased in W but not in B. Arachidonic acid (AA) did not change in either group. There was no change in calcium excretion in either group but oxalate and citrate excretion increased in W. We suggest that elongation of GLA to DGLA may occur more rapidly than desaturation of DGLA to AA in W and that depressed activity of the enzyme elongase may occur in B. Calciuric and citraturic effects may be dependent on the quantity of LA or on the mass ratio of LA/GLA in the FA supplement. Questions about the mooted DGLA-AA-oxaluria pathway arise. We speculate that there exists a potential for using GLA as a conservative treatment for hypocitraturia. The observation of different responses in B and W indicates that such differences may play a role in stone formation and prevention.}, }
@article {pmid28559311, year = {2017}, author = {Gyobu, S and Ishihara, K and Suzuki, J and Segawa, K and Nagata, S}, title = {Characterization of the scrambling domain of the TMEM16 family.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {24}, pages = {6274-6279}, pmid = {28559311}, issn = {1091-6490}, mesh = {Animals ; Anoctamins/*chemistry/genetics/*metabolism ; Calcium/metabolism ; Mice ; Phospholipid Transfer Proteins/*chemistry/genetics/*metabolism ; Phospholipids/chemistry/metabolism ; Point Mutation ; Protein Domains/genetics ; }, abstract = {The TMEM16 protein family has 10 members, each of which carries 10 transmembrane segments. TMEM16A and 16B are Ca[2+]-activated Cl[-] channels. Several other members, including TMEM16F, promote phospholipid scrambling between the inner and outer leaflets of a cell membrane in response to intracellular Ca[2+] However, the mechanism by which TMEM16 proteins translocate phospholipids in plasma membranes remains elusive. Here we show that Ca[2+]-activated, TMEM16F-supported phospholipid scrambling proceeds at 4 °C. Similar to TMEM16F and 16E, seven TMEM16 family members were found to carry a domain (SCRD; scrambling domain) spanning the fourth and fifth transmembrane segments that conferred scrambling ability to TMEM16A. By introducing point mutations into TMEM16F, we found that a lysine in the fourth transmembrane segment of the SCRD as well as an arginine in the third and a glutamic acid in the sixth transmembrane segment were important for exposing phosphatidylserine from the inner to the outer leaflet. However, their role in internalizing phospholipids was limited. Our results suggest that TMEM16 provides a cleft containing hydrophilic "stepping stones" for the outward translocation of phospholipids.}, }
@article {pmid28526969, year = {2017}, author = {Theka, T and Rodgers, A}, title = {Glycaemia and phosphatemia after oral glucose and maltitol ingestion in subjects from two different race groups: preliminary evidence of inter-race differences in metabolism and possible implications for urinary stone disease.}, journal = {International urology and nephrology}, volume = {49}, number = {8}, pages = {1369-1374}, pmid = {28526969}, issn = {1573-2584}, mesh = {Administration, Oral ; Adolescent ; Adult ; *Black People ; Blood Glucose/*metabolism ; Cross-Over Studies ; Glucose/administration &amp; dosage/metabolism ; Glycolysis ; Humans ; Male ; Maltose/administration &amp; dosage/analogs &amp; derivatives/metabolism ; Nephrolithiasis/ethnology ; Phosphates/*blood ; Random Allocation ; Risk Factors ; South Africa/epidemiology ; Sugar Alcohols/administration &amp; dosage/metabolism ; Sweetening Agents/administration &amp; dosage/metabolism ; *White People ; Young Adult ; }, abstract = {PURPOSE: Glucose (Glu) and maltitol (Mal) ingestion affect calciuria and phosphaturia. Renal phosphate leak involving hypophosphatemia is thought to be a mechanism. Inter-race differences in carbohydrate metabolism are known. We investigated the effects of Glu and Mal ingestion on glycaemia and phosphatemia in subjects from two race groups to better understand potential implications for nephrolithiasis.<br><br>METHODS: Healthy black (B) (n&#xa0;=&#xa0;8) and white (W) (n&#xa0;=&#xa0;8) males followed a self-selected standardized diet for 7 days and a strictly controlled standardized diet on Day 8. After an overnight fast, subjects provided blood samples prior to and 30&#xa0;min after ingestion of a randomly assigned solution of Glu or Mal. Blood Glu and serum phosphate were measured. Protocols were swapped after a 1-week washout period.<br><br>RESULTS: Following Glu ingestion, glycaemia increased significantly in W (4.8 vs 6.2&#xa0;mmol/l) but not in B (4.7 vs 5.3&#xa0;mmol/l) while phosphatemia decreased significantly in B (1.16 vs 1.01&#xa0;mmol/l) but not in W (1.24 vs 1.15&#xa0;mmol/l). After Mal ingestion, glycaemia increased significantly in B (4.7 vs 5.2&#xa0;mmol/l) but not in W (4.6 vs 5.9&#xa0;mmol/l), while phosphatemia decreased significantly in W (1.24 vs 1.18&#xa0;mmol/l) but not in B (1.17 vs 1.06&#xa0;mmol/l).<br><br>CONCLUSIONS: Our results suggest that enzymes which regulate glycolysis may be less active in B than in W, or expression of renal transcellular Glu transporters may be relatively inhibited in B. Effects on phosphatemia are carbohydrate- and race-dependent, thereby prohibiting speculation of a general algorithm linking these variables. Inter-race differences in metabolic handling of carbohydrates might impact on respective nephrolithiasis risk factors in such groups.}, }
@article {pmid28459860, year = {2017}, author = {Cybulski, TR and Boyden, ES and Church, GM and Tyo, KEJ and Kording, KP}, title = {Nucleotide-time alignment for molecular recorders.}, journal = {PLoS computational biology}, volume = {13}, number = {5}, pages = {e1005483}, pmid = {28459860}, issn = {1553-7358}, support = {DP1 NS087724/NS/NINDS NIH HHS/United States ; R01 MH103910/MH/NIMH NIH HHS/United States ; T32 GM008152/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Calcium/analysis/metabolism ; Computational Biology/*methods ; Computer Simulation ; *DNA/analysis/chemistry/metabolism ; DNA-Directed DNA Polymerase/metabolism ; Models, Biological ; Neurons/metabolism ; Neurosciences ; *Nucleotides/analysis/metabolism ; Single-Cell Analysis ; Time Factors ; }, abstract = {Using a DNA polymerase to record intracellular calcium levels has been proposed as a novel neural recording technique, promising massive-scale, single-cell resolution monitoring of large portions of the brain. This technique relies on local storage of neural activity in strands of DNA, followed by offline analysis of that DNA. In simple implementations of this scheme, the time when each nucleotide was written cannot be determined directly by post-hoc DNA sequencing; the timing data must be estimated instead. Here, we use a Dynamic Time Warping-based algorithm to perform this estimation, exploiting correlations between neural activity and observed experimental variables to translate DNA-based signals to an estimate of neural activity over time. This algorithm improves the parallelizability of traditional Dynamic Time Warping, allowing several-fold increases in computation speed. The algorithm also provides a solution to several critical problems with the molecular recording paradigm: determining recording start times and coping with DNA polymerase pausing. The algorithm can generally locate DNA-based records to within <10% of a recording window, allowing for the estimation of unobserved incorporation times and latent neural tunings. We apply our technique to an in silico motor control neuroscience experiment, using the algorithm to estimate both timings of DNA-based data and the directional tuning of motor cortical cells during a center-out reaching task. We also use this algorithm to explore the impact of polymerase characteristics on system performance, determining the precision of a molecular recorder as a function of its kinetic and error-generating properties. We find useful ranges of properties for DNA polymerase-based recorders, providing guidance for future protein engineering attempts. This work demonstrates a useful general extension to dynamic alignment algorithms, as well as direct applications of that extension toward the development of molecular recorders, providing a necessary stepping stone for future biological work.}, }
@article {pmid28400273, year = {2017}, author = {Fleet, JC}, title = {The role of vitamin D in the endocrinology controlling calcium homeostasis.}, journal = {Molecular and cellular endocrinology}, volume = {453}, number = {}, pages = {36-45}, pmid = {28400273}, issn = {1872-8057}, support = {R01 DK054111/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bone and Bones/metabolism ; Calcification, Physiologic ; Calcium/*metabolism ; Calcium, Dietary ; Endocrine System/*metabolism ; Gene Expression Regulation ; *Homeostasis ; Humans ; Intestinal Absorption ; Intestinal Mucosa/metabolism ; Kidney/metabolism ; Mice ; Models, Molecular ; Parathyroid Glands/metabolism ; Receptors, Calcitriol/*metabolism ; Vitamin D/*metabolism ; }, abstract = {Vitamin D and its' metabolites are a crucial part of the endocrine system that controls whole body calcium homeostasis. The goal of this hormonal control is to regulate serum calcium levels so that they are maintained within a very narrow range. To achieve this goal, regulatory events occur in coordination at multiple tissues, e.g. the intestine, kidney, bone, and parathyroid gland. Production of the vitamin D endocrine hormone, 1,25 dihydroxyvitamin D (1,25(OH)2 D) is regulated by habitual dietary calcium intake and physiologic states like growth, aging, and the menopause. The molecular actions of 1,25(OH)2 D on calcium regulating target tissues are mediated predominantly by transcription controlled by the vitamin D receptor. A primary role for 1,25(OH)2 D during growth is to increase intestinal calcium absorption so that sufficient calcium is available for bone mineralization. However, vitamin D also has specific actions on kidney and bone.}, }
@article {pmid28381520, year = {2017}, author = {Yiu, AJ and Ibeh, CL and Roy, SK and Bandyopadhyay, BC}, title = {Melamine induces Ca[2+]-sensing receptor activation and elicits apoptosis in proximal tubular cells.}, journal = {American journal of physiology. Cell physiology}, volume = {313}, number = {1}, pages = {C27-C41}, pmid = {28381520}, issn = {1522-1563}, support = {R01 DK102043/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Calcium/*metabolism ; Cell Line ; DNA Fragmentation ; Environmental Pollutants/*toxicity ; Epithelial Cells/cytology/*drug effects/metabolism ; Fibronectins/genetics/metabolism ; Gene Expression Regulation ; Kidney Tubules, Proximal/cytology/*drug effects/metabolism ; L-Lactate Dehydrogenase/metabolism ; Mitogen-Activated Protein Kinase 1/genetics/metabolism ; Mitogen-Activated Protein Kinase 3/genetics/metabolism ; Reactive Oxygen Species/agonists/metabolism ; Receptors, Calcium-Sensing/*agonists/genetics/metabolism ; Signal Transduction ; Spectrometry, Fluorescence ; Swine ; Time-Lapse Imaging ; Transforming Growth Factor beta1/genetics/metabolism ; Triazines/*toxicity ; }, abstract = {Melamine causes renal tubular cell injury through inflammation, fibrosis, and apoptosis. Although melamine affects the rise in intracellular Ca[2+] concentration ([Ca[2+]]i), reactive oxygen species (ROS) production, and proapoptotic pathway activation, the mechanism of upstream Ca[2+] signaling is unknown. Because melamine has some structural similarities with l-amino acids, which endogenously activate Ca[2+]-sensing receptors (CSR), we examined the effect of melamine on CSR-induced Ca[2+] signaling and apoptotic cell death. We show here that melamine activates CSR, causing a sustained Ca[2+] entry in the renal epithelial cell line, LLC-PK1. Moreover, such CSR stimulation resulted in a rise in [Ca[2+]]i, leading to enhanced ROS production. Furthermore, melamine-induced elevated [Ca[2+]]i and ROS production caused a dose-dependent increase in apoptotic (by DAPI staining, DNA laddering, and annexin V assay) and necrotic (propidium iodide staining) cell death. Upon examining the downstream mechanism, we found that transforming growth factor β1 (TGF-β1), which increases extracellular matrix genes and proapoptotic signaling, was also upregulated at lower doses of melamine, which could be due to an early event inducing apoptosis. Additionally, cells exposed to melamine displayed a rise in pERK activation and lactate dehydrogenase release resulting in cytotoxicity. These results offer a novel insight into the molecular mechanisms by which melamine exerts its effect on CSR, causing a sustained elevation of [Ca[2+]]i, leading to ROS generation, fibronectin production, proapoptotic pathway activation, and renal cell damage. Together, these results thus suggest that melamine-induced apoptosis and/or necrosis may subsequently result in acute kidney injury and promote kidney stone formation.}, }
@article {pmid28292388, year = {2017}, author = {Ather, MH and Sulaiman, MN and Siddiqui, I and Siddiqui, T}, title = {Tailored Metabolic Workup for Urolithiasis - The Debate Continues.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {27}, number = {2}, pages = {101-104}, pmid = {28292388}, issn = {1681-7168}, mesh = {Calcium/*metabolism ; *Disease Management ; Humans ; Oxalates/*metabolism ; *Practice Guidelines as Topic ; Recurrence ; Risk Factors ; Secondary Prevention/*standards ; *Urolithiasis/metabolism/prevention &amp; control/therapy ; }, abstract = {Urolithiasis is one of the commonest afflictions of the urinary tract. Stones are of various chemical compositions, some share some common etiology; but most are specific to the structure and composition of stone. In view of highly recurrent nature of this condition, it is logical to have strategies for prevention. However, due to multiple factors most patients receive no or fragmented information on prevention. The current controversy is to the extent of metabolic workup in adult first time stone former. This requires longitudinal studies to show benefit in prevention strategies. Patients at high risk can have recurrence in weeks to years, depending upon the composition and attending risk factor. They should be targeted with concentric and tailored prevention protocols. The major urological guidelines (EAU and AUA) recommend basic stone workup for all patients. However, indication for detailed workup are less well documented, so one potential solution is to tailor metaphylaxis strategies for individual patient.}, }
@article {pmid28229505, year = {2017}, author = {Ure, ME and Heydari, E and Pan, W and Ramesh, A and Rehman, S and Morgan, C and Pinsk, M and Erickson, R and Herrmann, JM and Dimke, H and Cordat, E and Lemaire, M and Walter, M and Alexander, RT}, title = {A variant in a cis-regulatory element enhances claudin-14 expression and is associated with pediatric-onset hypercalciuria and kidney stones.}, journal = {Human mutation}, volume = {38}, number = {6}, pages = {649-657}, doi = {10.1002/humu.23202}, pmid = {28229505}, issn = {1098-1004}, mesh = {Adolescent ; Binding Sites/genetics ; Calcium/blood ; Child ; Child, Preschool ; Claudins/*genetics ; Female ; Gene Expression Regulation/genetics ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Hypercalciuria/complications/*genetics/pathology ; Infant ; Kidney Calculi/complications/*genetics/pathology ; Male ; Polymorphism, Single Nucleotide/genetics ; Protein Binding/genetics ; Repressor Proteins/*genetics ; }, abstract = {The greatest risk factor for kidney stones is hypercalciuria, the etiology of which is largely unknown. A recent genome-wide association study (GWAS) linked hypercalciuria and kidney stones to a claudin-14 (CLDN14) risk haplotype. However, the underlying molecular mechanism was not delineated. Recently, renal CLDN14 expression was found to increase in response to increased plasma calcium, thereby inducing calciuria. We hypothesized therefore that some children with hypercalciuria and kidney stones harbor a CLDN14 variant that inappropriately increases gene expression. To test this hypothesis, we sequenced the CLDN14 risk haplotype in a cohort of children with idiopathic hypercalciuria and kidney stones. An intronic SNP was more frequent in affected children. Dual luciferase and cell-based assays demonstrated increased reporter or CLDN14 expression when this polymorphism was introduced. In silico studies predicted the SNP introduced a novel insulinoma-associated 1 (INSM1) transcription factor binding site. Consistent with this, repeating the dual luciferase assay in the presence of INSM1 further increased reporter expression. Our data suggest that children with the INSM1 binding site within the CLDN14 risk haplotype have a higher likelihood of hypercalciuria and kidney stones. Enhanced CLDN14 expression may play a role in the pathophysiology of their hypercalciuria.}, }
@article {pmid28188435, year = {2017}, author = {Kovacevic, L and Lu, H and Caruso, JA and Govil-Dalela, T and Thomas, R and Lakshmanan, Y}, title = {Marked increase in urinary excretion of apolipoproteins in children with nephrolithiasis associated with hypercalciuria.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {32}, number = {6}, pages = {1029-1033}, pmid = {28188435}, issn = {1432-198X}, support = {P30 ES020957/ES/NIEHS NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; S10 OD010700/OD/NIH HHS/United States ; }, mesh = {Adolescent ; Apolipoproteins/metabolism/*urine ; Calcium/metabolism/urine ; Child ; Chromatography, Liquid ; Citrates/urine ; Enzyme-Linked Immunosorbent Assay ; Fatty Acid-Binding Proteins/metabolism ; Female ; Humans ; Hypercalciuria/metabolism/*urine ; Kidney Calculi/metabolism/*urine ; Male ; Mass Spectrometry ; Pilot Projects ; Prospective Studies ; Proteomics/methods ; *Renal Elimination ; }, abstract = {BACKGROUND: Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters.<br><br>METHODS: Prospective, controlled, pilot study of pooled urine from CAL, CIT, and NM versus age- and gender-matched HCs, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Results were confirmed by ELISA performed on individual samples.<br><br>RESULTS: Of the 1,813 proteins identified, 230 met the above criteria. Of those, 5 proteins (apolipoprotein A-II [APOA2]; apolipoprotein A-IV [APOA4]; apolipoprotein C-III [APOA3]; fatty acid-binding protein, liver [FABPL]; fatty acid-binding protein, adipocyte [FABP4]) involved in lipid metabolism and transport were found in the CAL group, with significant differences compared with HCs. ELISA analysis indicated statistically significant differences in the urinary excretion of APOC3, APOA4, and FABPL in the CAL group compared with HCs. Twenty-four-hour urinary calcium excretion correlated significantly with concentrations of ApoC3 (r&#x2009;=&#x2009;0.77, p&#x2009;<&#x2009;0.001), and FABPL (r&#x2009;=&#x2009;0.80, p&#x2009;=&#x2009;0.005).<br><br>CONCLUSIONS: We provide proteomic data showing increased urinary excretion of lipid metabolism/transport-related proteins in children with kidney stones and hypercalciuria. These findings suggest that abnormalities in lipid metabolism might play a role in kidney stone formation.}, }
@article {pmid27981376, year = {2017}, author = {Johri, N and Jaeger, P and Ferraro, PM and Shavit, L and Nair, D and Robertson, WG and Gambaro, G and Unwin, RJ}, title = {Vitamin D deficiency is prevalent among idiopathic stone formers, but does correction pose any risk?.}, journal = {Urolithiasis}, volume = {45}, number = {6}, pages = {535-543}, pmid = {27981376}, issn = {2194-7236}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Calcium/*metabolism/urine ; Cholecalciferol/*adverse effects ; Cohort Studies ; Creatinine/urine ; Dietary Supplements/*adverse effects ; Female ; Humans ; Hypercalciuria/chemically induced/*urine ; Kidney Calculi/blood/epidemiology/*urine ; Male ; Middle Aged ; Phosphates/urine ; Prevalence ; Renal Elimination/drug effects ; Risk Factors ; Vitamin D/analogs &amp; derivatives/blood ; Vitamin D Deficiency/blood/drug therapy/*epidemiology/urine ; Young Adult ; }, abstract = {While vitamin D (vitD) deficiency is thought to contribute to poor health in a variety of ways and should be corrected, there is still concern about giving vitD supplements to patients with a history of nephrolithiasis. The aim is to study the prevalence of vitD deficiency and the effect on stone risk of cholecalciferol (vitD3) supplementation in a cohort of idiopathic stone formers (ISF). We screened for vitD deficiency and urinary measures of stone risk, comparing vitD deficient (serum 25-OH vitD ≤30 nmol/L; ≤12 ng/mL) with vitD insufficient (31-75 nmol/L; 13-30 ng/mL) or vitD replete (>75 nmol/L; >30 ng/mL); we investigated the effect of giving vitD3 (20,000 IU orally, weekly for 4 months) to 37 of the vitD deficients. Thirty-one percent (142/456) were vitD deficient, 57% (259/456) vitD insufficient, and the rest (12%) vitD replete (55/456). Comparison among the groups showed that baseline 24-h urinary measures related to stone risk expressed as concentration ratios over urine creatinine (Cr), such as U. Calcium/Cr, U. Oxalate/Cr, U. Citrate/Cr, and U. Uric acid/Cr were not significantly different. VitD3 supplementation did significantly increase serum 25-OH vitD levels and U. Phosphate/Cr ratios, as well as reduce serum parathyroid hormone (PTH) concentrations. Following vitD3 supplementation, there was an overall rise in 24-h urine calcium excretion, but it failed to reach statistical significance (p = 0.06). U. Calcium/Cr increased in 22 out of 37 patients (average increase +0.07 mmol/mmol), decreased in 14 (average decrease -0.13 mmol/mmol), and remained unchanged in 1; 6 out of 26 initially normocalciuric ISF developed hypercalciuria; and 6 out of 9 patients who became vitD replete were hypercalciuric after supplementation. It is appropriate to monitor urinary Ca excretion in vitD-supplemented stone formers, because it may reveal underlying hypercalciuria in some treated patients.}, }
@article {pmid27959841, year = {2016}, author = {Spivacow, FR and Del Valle, EE and Lores, E and Rey, PG}, title = {Kidney stones: Composition, frequency and relation to metabolic diagnosis.}, journal = {Medicina}, volume = {76}, number = {6}, pages = {343-348}, pmid = {27959841}, issn = {0025-7680}, mesh = {Adult ; Age Factors ; Argentina/epidemiology ; Calcium/metabolism ; Crystallography, X-Ray/methods ; Humans ; Kidney/metabolism ; Kidney Calculi/chemistry/*epidemiology/*etiology/*metabolism ; Male ; Metabolic Diseases/*complications/*epidemiology ; Middle Aged ; Reference Values ; Risk Assessment ; Risk Factors ; Sex Factors ; Uric Acid/metabolism ; Young Adult ; }, abstract = {Nephrolithiasis is one of the most frequent urologic diseases. The aim of this paper is to study the composition and frequency of 8854 patient kidney stones and in a subset of them their metabolic risk factors to be related to their type of calculi. Physicochemical and crystallographic methods were used to assess kidney stone composition. In a subset of 715 patients, we performed an ambulatory metabolic protocol with diagnostic purposes. From the total sample 79% of stones were made of calcium salts (oxalate and phosphate), followed by uric acid stones in 16.5%, calcium salts and uric acid in 2%, other salts in 1.9% and cystine in 0.6%. Male to female ratio was almost three times higher in calcium salts and other types of stones, reaching a marked male predominance in uric acid stones, M/F 18.8 /1.0. The major risk factors for calcium stones are idiopathic hypercalciuria, followed by unduly acidic urine pH and hyperuricosuria. In uric acid stones unduly acidic urine pH and less commonly hyperuricosuria are the most frequent biochemical diagnosis. Our results show that analysis of kidney stones composition and the corresponding metabolic diagnosis may provide a scientific basis for the best management and prevention of kidney stone formation, as well as it may help us to study the mechanisms of urine stone formation.}, }
@article {pmid27942796, year = {2017}, author = {Guerra, A and Ticinesi, A and Allegri, F and Nouvenne, A and Pinelli, S and Lauretani, F and Maggio, M and Cervellin, G and Borghi, L and Meschi, T}, title = {Calcium urolithiasis course in young stone formers is influenced by the strength of family history: results from a retrospective study.}, journal = {Urolithiasis}, volume = {45}, number = {6}, pages = {525-533}, pmid = {27942796}, issn = {2194-7236}, mesh = {Adolescent ; Adult ; Age Factors ; Calcium/*metabolism/urine ; Cross-Sectional Studies ; Female ; Humans ; Kidney Calculi/*epidemiology/etiology/urine ; Male ; Medical History Taking/*statistics &amp; numerical data ; Recurrence ; *Renal Elimination ; Retrospective Studies ; Risk Factors ; Sex Factors ; Young Adult ; }, abstract = {The role of the strength of family history of stones (FHS), i.e., degree of relatives with the disease, on the course of calcium urolithiasis (CU) is not fully understood, particularly in young patients where genetic background has the greatest influence on disease expression. Thus, with a retrospective cross-sectional design, we examined baseline clinical parameters and urinary chemistries of 369 subjects (196 M) with CU and 96 controls (41 M) aged between 15 and 25 at the time of the first visit at our stone clinic. Subjects with metabolic syndrome traits, known causes of CU or CU onset before the age of 15 were excluded. Clinical and metabolic parameters were compared among stone formers (SF) and controls, stratified by gender, the presence and type of FHS determined through the kinship coefficient of relatives with stones. No significant differences in clinical course were found between SF with and without FHS, except for the presence of bilateral stones (OR 2.01, 95% CI 1.20-3.39, p < 0.01). A significant age-, sex- and disease duration-adjusted trend for a higher number of colics (p for trend = 0.001), number of stones (p for trend = 0.002), stone rate (p for trend = 0.003) and the presence of retained stones (OR 1.60, 95% CI 1.14-2.21, p = 0.006) was detected with increasing FHS strength. Urinary chemistries were unaffected by FHS in both SF and controls, except for a higher calcium excretion in females with FHS (p < 0.05). The type of FHS, thus, significantly influences the clinical course of CU in young SF, mainly irrespective of urinary factors.}, }
@article {pmid27941176, year = {2016}, author = {Bahadoran, H and Naghii, MR and Mofid, M and Asadi, MH and Ahmadi, K and Sarveazad, A}, title = {Protective effects of boron and vitamin E on ethylene glycol-induced renal crystal calcium deposition in rat.}, journal = {Endocrine regulations}, volume = {50}, number = {4}, pages = {194-206}, doi = {10.1515/enr-2016-0021}, pmid = {27941176}, issn = {1210-0668}, mesh = {Animals ; Antioxidants/*pharmacology ; Boron/*pharmacology ; Calcium/*metabolism ; Ethylene Glycol/*toxicity ; Kidney/*drug effects/metabolism/pathology ; Kidney Calculi/*chemically induced ; Kidney Tubules/drug effects/metabolism/pathology ; Male ; Oxidative Stress/drug effects ; Rats ; Rats, Wistar ; Trace Elements/*pharmacology ; Vitamin E/*pharmacology ; }, abstract = {OBJECTIVES: Kidney stone disease is a common form of renal disease. Antioxidants, such as vitamin E (Vit E) and boron, are substances that reduce the damage caused by oxidation.<br><br>METHODS: Adult male rats were divided into 5 groups (n=6). In group 1, rats received standard food and water for 28 days (control group); in group 2, standard rodent food and water with 0.75% ethylene glycol/d (dissolved in drinking water) (EG Group); in group 3, similar to group 2, with 3 mg of boron/d (dissolved in water) (EG+B Group); in group 4, similar to group 2, with 200 IU of vitamin E injected intraperitoneally on the first day and the 14th day, (EG+Vit E Group); in group 5, mix of groups 3 and 4, respectively (EG+B+Vit E Group).<br><br>RESULTS: Kidney sections showed that crystals in the EG group increased significantly in comparison with the control group. Crystal calcium deposition score in groups of EG+B (160), EG+Vit E, and EG+B+Vit E showed a significant decrease compared to EG group. Measurement of the renal tubules area and renal tubular epithelial histological score showed the highest significant dilation in the EG group. Tubular dilation in the EG+B+Vit E group decreased compared to the EG+B and EG+Vit E groups.<br><br>CONCLUSIONS: Efficient effect of boron and Vit E supplements, separately and in combination, has a complimentary effect in protection against the formation of kidney stones, probably by decreasing oxidative stress.}, }
@article {pmid27924845, year = {2016}, author = {Peerapen, P and Thongboonkerd, V}, title = {Caffeine prevents kidney stone formation by translocation of apical surface annexin A1 crystal-binding protein into cytoplasm: In vitro evidence.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {38536}, pmid = {27924845}, issn = {2045-2322}, mesh = {Animals ; Annexin A1/*metabolism ; Caffeine/pharmacology/*therapeutic use ; Calcium/metabolism ; Calcium Oxalate/chemistry/*metabolism ; Cell Membrane/drug effects/*metabolism ; Crystallization ; Cytoplasm/*metabolism ; Dogs ; Intracellular Space/metabolism ; Kidney Calculi/*drug therapy/metabolism/*prevention &amp; control ; Madin Darby Canine Kidney Cells ; Protein Transport/drug effects ; }, abstract = {Recent large 3 cohorts have shown that caffeinated beverage consumption was associated with lower risk of kidney stone disease. However, its protective mechanisms remained unknown and had not been previously investigated. We thus evaluated protective effects of caffeine (1 μM-10 mM) on calcium oxalate monohydrate (COM) kidney stone formation, using crystallization, crystal growth, cell-crystal adhesion, Western blotting, and immunofluorescence assays. The results showed that caffeine reduced crystal number but, on the other hand, increased crystal size, resulting in unchanged crystal mass, consistent with crystal growth that was not affected by caffeine. However, caffeine significantly decreased crystal-binding capacity of MDCK renal tubular cells in a dose-dependent manner. Western blotting and immunofluorescence study of COM crystal-binding proteins revealed significantly decreased level of annexin A1 on apical surface and its translocation into cytoplasm of the caffeine-treated cells, but no significant changes in other COM crystal-binding proteins (annexin A2, α-enolase, HSP70, and HSP90) were observed. Moreover, caffeine decreased intracellular [Ca[2+]] but increased [Ca[2+]] secretory index. Taken together, our findings showed an in vitro evidence of the protective mechanism of caffeine against kidney stone formation via translocation of annexin A1 from apical surface into cytoplasm to reduce the crystal-binding capacity of renal tubular epithelial cells.}, }
@article {pmid27915449, year = {2017}, author = {Corre, T and Olinger, E and Harris, SE and Traglia, M and Ulivi, S and Lenarduzzi, S and Belge, H and Youhanna, S and Tokonami, N and Bonny, O and Houillier, P and Polasek, O and Deary, IJ and Starr, JM and Toniolo, D and Gasparini, P and Vollenweider, P and Hayward, C and Bochud, M and Devuyst, O}, title = {Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.}, journal = {Pflugers Archiv : European journal of physiology}, volume = {469}, number = {1}, pages = {91-103}, pmid = {27915449}, issn = {1432-2013}, support = {BB/F019394/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MC_PC_U127561128/MRC_/Medical Research Council/United Kingdom ; MR/K026992/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Animals ; Calcium/metabolism/*urine ; Claudins/*genetics ; Humans ; Kidney Tubules/metabolism ; Magnesium/metabolism/*urine ; Polymorphism, Single Nucleotide/*genetics ; Urine/*chemistry ; }, abstract = {The nature and importance of genetic factors regulating the differential handling of Ca[2+] and Mg[2+] by the renal tubule in the general population are poorly defined. We conducted a genome-wide meta-analysis of urinary magnesium-to-calcium ratio to identify associated common genetic variants. We included 9320 adults of European descent from four genetic isolates and three urban cohorts. Urinary magnesium and calcium concentrations were measured centrally in spot urine, and each study conducted linear regression analysis of urinary magnesium-to-calcium ratio on ~2.5 million single-nucleotide polymorphisms (SNPs) using an additive model. We investigated, in mouse, the renal expression profile of the top candidate gene and its variation upon changes in dietary magnesium. The genome-wide analysis evidenced a top locus (rs172639, p = 1.7 × 10[-12]), encompassing CLDN14, the gene coding for claudin-14, that was genome-wide significant when using urinary magnesium-to-calcium ratio, but not either one taken separately. In mouse, claudin-14 is expressed in the distal nephron segments specifically handling magnesium, and its expression is regulated by chronic changes in dietary magnesium content. A genome-wide approach identified common variants in the CLDN14 gene exerting a robust influence on the differential excretion of Mg[2+] over Ca[2+] in urine. These data highlight the power of urinary electrolyte ratios to unravel genetic determinants of renal tubular function. Coupled with mouse experiments, these results support a major role for claudin-14, a gene associated with kidney stones, in the differential paracellular handling of divalent cations by the renal tubule.}, }
@article {pmid27889417, year = {2017}, author = {Tasian, GE and Ross, ME and Song, L and Grundmeier, RW and Massey, J and Denburg, MR and Copelovitch, L and Warner, S and Chi, T and Killilea, DW and Stoller, ML and Furth, SL}, title = {Dietary Zinc and Incident Calcium Kidney Stones in Adolescence.}, journal = {The Journal of urology}, volume = {197}, number = {5}, pages = {1342-1348}, pmid = {27889417}, issn = {1527-3792}, support = {K23 DK093556/DK/NIDDK NIH HHS/United States ; K23 DK106428/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Calcium/metabolism ; Case-Control Studies ; Child ; Diet/adverse effects ; Female ; Humans ; Kidney Calculi/*epidemiology/etiology ; Male ; Risk Factors ; Urinalysis ; Zinc/*administration &amp; dosage/adverse effects/urine ; }, abstract = {PURPOSE: We determined the association between dietary zinc intake and incident calcium kidney stones in adolescents. We also examined the relationship between dietary zinc intake and urinary zinc excretion between cases and controls.<br><br>MATERIALS AND METHODS: We conducted a nested case-control study within a large pediatric health care system. Three 24-hour dietary recalls and spot urine chemistry analyses were obtained for 30 participants 12 to 18 years old with a first idiopathic calcium based kidney stone and 30 healthy controls matched for age, sex, race and month of enrollment. Conditional logistic regression models were used to estimate the association between daily zinc intake and incident calcium kidney stones, adjusting for dietary phytate, protein, calcium, sodium and oxalate. Multivariable linear regression was used to estimate the association between dietary and urine zinc, adjusting for urine creatinine and dietary phytate and calcium.<br><br>RESULTS: Cases had lower daily zinc intake (8.1 mg) than controls (10 mg, p&#xa0;=&#xa0;0.029). Daily zinc intake of boys and girls with calcium stones was 2 mg and 1.2&#xa0;mg less, respectively, than the daily intake recommended by the Institute of Medicine. Odds of incident stones were reduced by 13% for every 1 mg increase in daily zinc intake (OR 0.87, 95% CI 0.75-0.99). There was an estimated 4.5 &#x3bc;g/dl increase in urine zinc for every 1 mg increase in dietary zinc (p = 0.009), with weak evidence of a smaller increase in urine zinc in cases than in controls (interaction p = 0.08).<br><br>CONCLUSIONS: Decreased dietary zinc intake was independently associated with incident calcium nephrolithiasis in this population of adolescents.}, }
@article {pmid27604776, year = {2016}, author = {Malihi, Z and Wu, Z and Stewart, AW and Lawes, CM and Scragg, R}, title = {Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis.}, journal = {The American journal of clinical nutrition}, volume = {104}, number = {4}, pages = {1039-1051}, doi = {10.3945/ajcn.116.134981}, pmid = {27604776}, issn = {1938-3207}, mesh = {Adult ; Aged ; Aged, 80 and over ; Calcium/*metabolism ; Dietary Supplements/*adverse effects ; Female ; Humans ; Hypercalcemia/*etiology ; Hypercalciuria/*etiology ; Kidney Calculi/*etiology ; Male ; Middle Aged ; Vitamin D/administration &amp; dosage/*adverse effects/analogs &amp; derivatives/blood ; Vitamins/administration &amp; dosage/*adverse effects/blood ; Young Adult ; }, abstract = {BACKGROUND: Vitamin D supplementation is increasingly being used in higher doses in randomized controlled trials (RCTs). However, adverse events from very large annual doses of vitamin D have been shown in 2 RCTs, whereas in a third RCT, low-dose vitamin D, with calcium supplements, was shown to increase kidney stone risk.<br><br>OBJECTIVE: We analyzed the side effects related to calcium metabolism in RCTs, specifically hypercalcemia, hypercalciuria, and kidney stones, in participants who were given vitamin D supplements for &#x2265;24 wk compared with in subjects in the placebo arm.<br><br>DESIGN: The following 3 main online databases were searched: Ovid Medline (PubMed), EMBASE, and the Cochrane Library. Software was used for the meta-analysis.<br><br>RESULTS: A total of 48 studies with 19,833 participants were identified, which reported &#x2265;1 of the following side effects: hypercalcemia, hypercalciuria, or kidney stones. Of these studies, kidney stones were reported in only 9 trials with a tendency for fewer subjects reporting stones in the vitamin D arm than in the placebo arm (RR: 0.66, 95% CI: 0.41, 1.09; P = 0.10). In 37 studies, hypercalcemia was shown with increased risk shown for the vitamin D group (RR: 1.54; 95% CI: 1.09, 2.18; P = 0.01). Similar increased risk of hypercalciuria was shown in 14 studies for the vitamin D group (RR: 1.64; 95% CI: 1.06, 2.53; P = 0.03). In subgroup analyses, it was shown that the effect of vitamin D supplementation on risk of hypercalcemia, hypercalciuria, or kidney stones was not modified by baseline 25-hydroxyvitamin D, vitamin D dose and duration, or calcium co-supplementation.<br><br>CONCLUSIONS: Long-term vitamin D supplementation resulted in increased risks of hypercalcemia and hypercalciuria, which were not dose related. However, vitamin D supplementation did not increase risk of kidney stones. Additional large RCTs of long-term vitamin D supplementation are required to confirm these findings.}, }
@article {pmid27545632, year = {2016}, author = {Vitale, C and Bermond, F and Rodofili, A and Soragna, G and Marcuccio, C and Tricerri, A and Marangella, M}, title = {[The effects of Cinacalcet in renal stone formers with primary hyperparathyroidism].}, journal = {Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia}, volume = {33}, number = {4}, pages = {}, pmid = {27545632}, issn = {1724-5990}, mesh = {Calcimimetic Agents/*therapeutic use ; Cinacalcet/*therapeutic use ; Female ; Humans ; Hyperparathyroidism, Primary/*complications ; Kidney Calculi/*etiology/*prevention &amp; control ; Male ; Middle Aged ; Retrospective Studies ; }, abstract = {Primary hyperparathyroidism (PHPT) may favor nephrolithiasis mainly through an increase in calcium and phosphate urinary excretion. Cinacalcet exhibits good efficacy to control hypercalcemia in PHPT, but it is not so far known whether it might be a useful tool to prevent stone recurrences. Of 67 patients with PHPT and recurrent nephrolithiasis, 55 underwent parathyroidectomy (PTX) and 12, not eligible to PTX, were prescribed Cinacalcet. All the patients were evaluated for mineral metabolism, including estimation of state of saturation for calcium oxalate (CaOx) and brushite (bsh), both at baseline and after either PTX or Cinacalcet. PTX compared to baseline reduced PTH (4617 vs 15786 pg/mL, p<0.01), calcemia (9.40.5 vs 11.30.9 mg/dL, p<0.01), calciuria (3.62.3 vs 9.24.5 mmol/24h, p<0.01), phosphaturia (18.47.1 vs 21.99.9 mmol/24h, p<0.05), CaOx (4.73.9 vs 9.86.8, p<0.01) and bsh (1.10.9 vs 3.22.2, p<0.01). Cinacalcet decreased both PTH (13379 vs 17187 pg/mL, p<0.05) and calcemia (9.70.6 vs 11.20.8 mg/dL, p<0.001), whereas no change was seen in calciuria (7.42.2 vs 7.42.4 mmol/24h, p=ns), phosphaturia (21.97.3 vs 23.06.5 mmol/24h, p=ns), CaOx (6.92.7 vs 5.42.5, p=ns) and bsh (1.71.1 vs 1.31.3, p=ns). We conclude that in patients with PHPT, PTX is able to decrease the risk for crystallization of calcium salts, whereas calcimimetic Cinacalcet did not. Therefore, in patients with PHPT complicated with nephrolithiasis only PTX can improve urine biochemistries thereby reducing the risk for recurrent calcium stone disease.}, }
@article {pmid27541288, year = {2017}, author = {Gönüllü, E and Bilge, N&#x15e;Y and Cansu, DU and Bekmez, M and Musmul, A and Akçar, N and Kaşifoğlu, T and Korkmaz, C}, title = {Risk factors for urolithiasis in patients with ankylosing spondylitis: a prospective case-control study.}, journal = {Urolithiasis}, volume = {45}, number = {4}, pages = {353-357}, pmid = {27541288}, issn = {2194-7236}, mesh = {Adult ; Calcium/*blood/metabolism/urine ; Case-Control Studies ; Female ; Humans ; Immunoglobulin A/*blood ; Kidney/metabolism ; Kidney Calculi/blood/*epidemiology/urine ; Magnesium/blood ; Male ; Middle Aged ; Parathyroid Hormone/blood ; Phosphates/blood ; Prospective Studies ; Renal Elimination ; Risk Factors ; Spondylitis, Ankylosing/blood/*epidemiology/urine ; }, abstract = {It has been reported that renal stone formation increased in patients with ankylosing spondylitis (AS). However, its reason remains unclear. The aim of this study was to evaluate serially the possible risk factors for renal stone formation in AS patients. Two groups consisted of AS patients with renal stone (n = 30), AS patients without renal stone (n = 30), and 20 healthy controls (HC) were included to the study. Parathyroid hormone, calcium, magnesium, phosphorus and immunoglobulin A levels and 24 h urine were evaluated at baseline, and three times monthly. Serum calcium levels were higher in AS patients with urolithiasis than those without at baseline and third-month evaluation (baseline: 9.53 ± 0.3 vs 9.32 ± 0.3 mg/dl; p < 0.03; at third-month evaluation: 9.74 ± 0.2 vs 9.56 ± 0.3 mg/dl; p < 0.01). No significant differences were found between groups in terms of PTH and magnesium levels. In all evaluation times, although urinary calcium excretion was higher in AS patients with urolithiasis than in those without, it did not reach a statistical significance. IgA levels were significantly higher in renal stone sufferers than HC patients in all evaluation times.AS patients with urolithiasis also had high IgA levels compared with AS patients without renal stone at the second-month evaluation time (276 ± 102 vs 219 ± 104 mg/dl, p < 0.002). Increased levels of serum calcium and IgA levels as well as family history for urolithiasis may be an indicator of the development of urolithiasis in AS patients.}, }
@article {pmid27507467, year = {2017}, author = {Israr, B and Frazier, RA and Gordon, MH}, title = {Enzymatic hydrolysis of phytate and effects on soluble oxalate concentration in foods.}, journal = {Food chemistry}, volume = {214}, number = {}, pages = {208-212}, doi = {10.1016/j.foodchem.2016.07.044}, pmid = {27507467}, issn = {1873-7072}, mesh = {6-Phytase/*pharmacology ; Calcium/metabolism ; Fabaceae/*chemistry/drug effects ; Hordeum/*chemistry/drug effects ; Hydrolysis ; Oxalates/*analysis ; Phytic Acid/*metabolism ; Triticum/*chemistry/drug effects ; }, abstract = {Soluble oxalate in foods is major concern for kidney stone formers due to its tendency to increase urinary oxalate concentration. Phytate forms complexes with cations, which increases soluble oxalate by making cations unavailable to precipitate oxalate. Thus, in order to reduce soluble oxalate, bran samples (wheat, oat and barley) and bean samples (red kidney bean and white bean) were treated with phytase. Release of phosphate after phytate degradation and its association with calcium was determined. Phosphate concentration increased after application of phytase in all samples, but effect on soluble oxalate concentration varied. Wheat and oat bran showed significant reduction (P<0.05) in soluble oxalate compared to bean samples. Wheat bran, oat bran and white bean had a lower calcium:phosphate ratio than barley bran and red kidney beans. Correlation of the calcium:phosphate molar ratio with release of phosphate depends on concentration of calcium ions and this influences soluble oxalate concentration.}, }
@article {pmid27284011, year = {2016}, author = {Vezzoli, G and Macrina, L and Rubinacci, A and Spotti, D and Arcidiacono, T}, title = {Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones.}, journal = {Clinical journal of the American Society of Nephrology : CJASN}, volume = {11}, number = {8}, pages = {1450-1455}, pmid = {27284011}, issn = {1555-905X}, mesh = {Adult ; *Bone Density ; Calcium/*metabolism ; Duodenum/physiopathology ; Female ; Humans ; Hypercalciuria/*complications/*metabolism ; *Intestinal Absorption ; Jejunum/physiopathology ; Kidney Calculi/*complications ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Strontium/blood/urine ; }, abstract = {BACKGROUND AND OBJECTIVES: Idiopathic hypercalciuria is a frequent defect in calcium kidney stone formers that is associated with high intestinal calcium absorption and osteopenia. Characteristics distinguishing hypercalciuric stone formers from hypercalciuric patients without kidney stone history (HNSFs) are unknown and were explored in our study.<br><br>We compared 172 hypercalciuric stone formers with 36 HNSFs retrospectively selected from patients referred to outpatient clinics of the San Raffaele Hospital in Milan from 1998 to 2003. Calcium metabolism and lumbar bone mineral density were analyzed in these patients. A strontium oral load test was performed: strontium was measured in 240-minute urine and serum 30, 60, and 240 minutes after strontium ingestion; serum strontium concentration-time curve and renal strontium clearance were evaluated to estimate absorption and excretion of divalent cations.<br><br>RESULTS: Serum strontium concentration-time curve (P<0.001) and strontium clearance (4.9&#xb1;1.3 versus 3.5&#xb1;2.7 ml/min; P<0.001) were higher in hypercalciuric stone formers than HNSFs, respectively. The serum strontium-time curve was also higher in hypercalciuric stone formers with low bone mineral density (n=42) than in hypercalciuric stone formers with normal bone mineral density (n=130; P=0.03) and HNSFs with low (n=22; P=0.01) or normal bone mineral density (n=14; P=0.02). Strontium clearance was greater in hypercalciuric stone formers with normal bone mineral density (5.3&#xb1;3.4 ml/min) than in hypercalciuric stone formers and HNSFs with low bone mineral density (3.6&#xb1;2.5 and 3.1&#xb1;2.5 ml/min, respectively; P=0.03). Multivariate regression analyses displayed that strontium absorption at 30 minutes was positively associated calcium excretion (P=0.03) and negatively associated with lumbar bone mineral density z score (P=0.001) in hypercalciuric stone formers; furthermore, hypercalciuric patients in the highest quartile of strontium absorption had increased stone production risk (odds ratio, 5.06; 95% confidence interval, 1.2 to 20.9; P=0.03).<br><br>CONCLUSIONS: High calcium absorption in duodenum and jejunum may expose hypercalciuric patients to the risk of stones because of increased postprandial calcium concentrations in urine and tubular fluid. High calcium absorption may identify patients at risk of bone loss among stone formers.}, }
@article {pmid27068369, year = {2016}, author = {Arrabal-Polo, M&#xc1; and del Carmen Cano-García, M and Arrabal-Martín, M}, title = {[The fasting calcium/creatinine ratio in patients with calcium stones and the relation with hypercalciuria and phosphocalcium metabolism].}, journal = {Archivos espanoles de urologia}, volume = {69}, number = {3}, pages = {117-120}, pmid = {27068369}, issn = {0004-0614}, mesh = {Calcium/metabolism/*urine ; Creatinine/*urine ; Cross-Sectional Studies ; Fasting ; Female ; Humans ; Hypercalciuria/*etiology ; Kidney Calculi/*complications/*urine ; Male ; Middle Aged ; Phosphorus/metabolism ; }, abstract = {OBJECTIVE: To determine the importance of fasting calcium/creatinine ratio in patients with calcium stones and its relation with hypercalciuria and phospho-calcium metabolism.<br><br>METHODS: Cross-sectional study including 143 patients divided into two groups according to fasting calcium/creatinine. Group 1: 66 patients (calcium/ creatinine<0.11); Group 2: 77 patients (calcium/ creatinine>0.11). A comparative study is performed between groups including phospho-calcium metabolism parameters and excretion of urinary lithogenic markers. Linear correlation studying calciuria and fasting calcium/ creatinine was performed. SPSS 17.0 statistical analysis software was used, considering p&#x2264;0.05.<br><br>RESULTS: It is noteworthy that group 2 had increased 24 h urine calcium excretion in comparison to group 1 (229.3 vs 158.1; p=0.0001) and calcium/citrate (0.47 vs 0.34; p=0.001). There is a positive and significant correlation between calcium levels in 24 h urine and fasting calcium/creatinine (R=0.455; p=0.0001) and a cutoff is set at 0.127 (sensitivity 72%, specificity 66%) to determine hypercalciuria (>260 mg in 24 h).<br><br>CONCLUSION: Increased fasting calcium/creatinine determines increased 24 hours calcium excretion, although the sensitivity and specificity to determine hypercalciuria is not high.}, }
@article {pmid27009338, year = {2016}, author = {Moor, MB and Bonny, O}, title = {Ways of calcium reabsorption in the kidney.}, journal = {American journal of physiology. Renal physiology}, volume = {310}, number = {11}, pages = {F1337-50}, doi = {10.1152/ajprenal.00273.2015}, pmid = {27009338}, issn = {1522-1466}, mesh = {Animals ; Calcium/*metabolism ; Claudins/metabolism ; Feedback, Physiological/*physiology ; Homeostasis/*physiology ; Humans ; Hypercalciuria/metabolism ; Kidney/*metabolism ; Parathyroid Hormone/metabolism ; Receptors, Calcium-Sensing/metabolism ; }, abstract = {The role of the kidney in calcium homeostasis has been reshaped from a classic view in which the kidney was regulated by systemic calcitropic hormones such as vitamin D3 or parathyroid hormone to an organ actively taking part in the regulation of calcium handling. With the identification of the intrinsic renal calcium-sensing receptor feedback system, the regulation of paracellular calcium transport involving claudins, and new paracrine regulators such as klotho, the kidney has emerged as a crucial modulator not only of calciuria but also of calcium homeostasis. This review summarizes recent molecular and endocrine contributors to renal calcium handling and highlights the tight link between calcium and sodium reabsorption in the kidney.}, }
@article {pmid26969574, year = {2017}, author = {Ferraro, PM and Curhan, GC and D'Addessi, A and Gambaro, G}, title = {Risk of recurrence of idiopathic calcium kidney stones: analysis of data from the literature.}, journal = {Journal of nephrology}, volume = {30}, number = {2}, pages = {227-233}, pmid = {26969574}, issn = {1724-6059}, mesh = {Calcium/*metabolism ; Humans ; Kidney Calculi/epidemiology/metabolism/*therapy ; Randomized Controlled Trials as Topic ; Recurrence ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Nephrolithiasis is a frequent condition. While it is generally accepted that such condition carries a risk of recurrence over time, the exact risk and its predictors have been rarely quantitated. We aimed to estimate recurrence of kidney stones, overall and in specific subgroups, from randomized controlled trials (RCTs) of calcium stone formers.<br><br>METHODS: Systematic review of RCTs of adult patients with idiopathic calcium kidney stones. Recurrence rates analyzed in subgroups based on type of intervention and other characteristics, using Poisson regression models.<br><br>RESULTS: The analysis included 21 RCTs with 2168 participants over a median follow-up of 3.2&#xa0;years (range 0.5-9.7). The median recurrence of kidney stones was 15 per 100 person-years (range 0-110). Recurrence was higher in those with two or more previous stone episodes compared to those with a single episode at enrolment (16 vs. 6 per 100 person-years, p&#xa0;<&#xa0;0.001) and in those untreated or treated with dietary changes compared to those treated with drugs (26 vs. 23 vs. 9 per 100 person-years, p&#xa0;<&#xa0;0.001). The effect of drugs on recurrence seemed to be beneficial only among those with two or more previous stone episodes.<br><br>CONCLUSIONS: The overall recurrence rate of stones depends on factors such as previous stone history and type of treatment. Dietary approaches seem to be more effective among single stone formers, whereas drugs seem to be more effective among recurrent stone formers.}, }
@article {pmid26932705, year = {2015}, author = {Pramono, LA and Larasati, D and Yossy, Y and Harbuwono, DS and Soebardi, S}, title = {Recurrent Bilateral Staghorn Stones as a Manifestation of Primary Hyperparathyroidism due to Parathyroid Adenoma.}, journal = {Acta medica Indonesiana}, volume = {47}, number = {4}, pages = {348-351}, pmid = {26932705}, issn = {0125-9326}, mesh = {Adenoma/*complications/diagnosis ; Adult ; Biopsy ; Calcium/*metabolism ; Diagnosis, Differential ; Female ; Humans ; Hyperparathyroidism, Primary/diagnosis/*etiology ; Hyperplasia ; Parathyroid Glands/diagnostic imaging/metabolism/*pathology ; Parathyroid Neoplasms/*complications/diagnosis ; Recurrence ; Tomography, X-Ray Computed ; }, abstract = {Primary hyperparathyroidism is a medical condition caused by overactive of parathyroid gland. It is most commonly caused by solitary adenoma of the parathyroid gland. Other causes of this condition are hyperplasia, multiple adenomas, and parathyroid cancer. Primary hyperparathyroidism has some metabolic consequences in the calcium metabolism. Hypercalcemia in patient with primary hyperparathyroidism will resulted to the most important comorbidity that is chronic deposition of calcium in the kidney forming nephrolithiasis or other urolithiasis. It is not uncommon, patient with parathyroid adenoma come to health care professionals with the chief complain of recurrence nephrolithiasis.}, }
@article {pmid26887716, year = {2016}, author = {Assimos, DG}, title = {Re: Altered Calcium and Vitamin D Homeostasis in First-Time Calcium Kidney Stone-Formers.}, journal = {The Journal of urology}, volume = {195}, number = {3}, pages = {658-659}, doi = {10.1016/j.juro.2015.12.020}, pmid = {26887716}, issn = {1527-3792}, mesh = {Calcium/*metabolism ; Ergocalciferols/*metabolism ; Female ; *Homeostasis ; Humans ; Kidney Calculi/*metabolism ; Male ; }, }
@article {pmid26856738, year = {2016}, author = {Arrabal-Martín, M and González-Torres, S and Cano-García, MC and Poyatos-Andújar, A and Abad-Menor, F and Arrabal-Polo, MA}, title = {Treatment with hydrochlorothiazide and alendronate in patients with stones and bone mineral density loss. Evolution of bone metabolism and calciuria with medical treatment.}, journal = {Archivos espanoles de urologia}, volume = {69}, number = {1}, pages = {9-18}, pmid = {26856738}, issn = {0004-0614}, mesh = {Alendronate/*therapeutic use ; *Bone Density ; *Bone Remodeling ; Calcium/blood/urine ; Creatinine/blood ; Humans ; Hydrochlorothiazide/*therapeutic use ; Prospective Studies ; Urinary Calculi/*drug therapy ; }, abstract = {OBJECTIVES: Treatment of calcium stones is based on diet and pharmacological measures such as the use of thiazides and other drugs. The aim of this study is to assess the effect of alendronate on hydrochlorothiazide on urinary calcium and bone mineral density in patients with calcium stones.<br><br>METHODS: Prospective observational study involving 77 patients with relapsing calcium stones divided into 2 groups according to treatment received. Group 1: 36 patients treated with alendronate 70 mg/week; Group 2: 41 patients treated with hydrochlorothiazide 50 mg/day. All patients receive diet recommendations and fluid intake. Studied and analyzed among other variables were bone mineral density, bone turnover markers and calciuria before and after 2 years of treatment. Statistical study with SPSS 17.0, statistical significance p<0.05.<br><br>RESULTS: No statistically significant differences in the distribution by sex or age of the patients between groups. In group 1 statistically a significant decrease was observed in the &#x392;-crosslaps and improvement in bone mineral density, along with decreased urinary calcium after 2 years of treatment. In Group 2 statistically significant decrease in urinary calcium and fasting calcium/creatinine was seen, along with improvement in bone mineral density after 2 years of treatment. In group 1, there is a more obvious and significant improvement in bone mineral density compared to 2 and &#x392;-crosslaps decrease. However, in group 2 the decrease in urinary calcium and calcium/creatinine was more significant than in group 1.<br><br>CONCLUSION: Treatment with thiazide decrease calciuria and produces an improvement in bone mineral density, although not in the same range as treatment with alendronate.}, }
@article {pmid26657998, year = {2015}, author = {Samoshkin, A and Convertino, M and Viet, CT and Wieskopf, JS and Kambur, O and Marcovitz, J and Patel, P and Stone, LS and Kalso, E and Mogil, JS and Schmidt, BL and Maixner, W and Dokholyan, NV and Diatchenko, L}, title = {Structural and functional interactions between six-transmembrane μ-opioid receptors and β2-adrenoreceptors modulate opioid signaling.}, journal = {Scientific reports}, volume = {5}, number = {}, pages = {18198}, pmid = {26657998}, issn = {2045-2322}, support = {T90 DE021986/DE/NIDCR NIH HHS/United States ; P30 NS045892/NS/NINDS NIH HHS/United States ; 1T90DE021986/DE/NIDCR NIH HHS/United States ; R01 DE019796/DE/NIDCR NIH HHS/United States ; 1R41DA032293/DA/NIDA NIH HHS/United States ; P01 NS045685/NS/NINDS NIH HHS/United States ; R41 DA032293/DA/NIDA NIH HHS/United States ; R01DE019796/DE/NIDCR NIH HHS/United States ; }, mesh = {Analgesics, Opioid/*metabolism ; Animals ; Calcium/metabolism ; Ganglia/metabolism ; Gene Expression ; Humans ; Ligands ; Mice ; Models, Molecular ; Molecular Conformation ; Neurons/metabolism ; Protein Binding ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism ; Receptors, Opioid, mu/*chemistry/genetics/*metabolism ; *Signal Transduction ; Structure-Activity Relationship ; }, abstract = {The primary molecular target for clinically used opioids is the μ-opioid receptor (MOR). Besides the major seven-transmembrane (7TM) receptors, the MOR gene codes for alternatively spliced six-transmembrane (6TM) isoforms, the biological and clinical significance of which remains unclear. Here, we show that the otherwise exclusively intracellular localized 6TM-MOR translocates to the plasma membrane upon coexpression with β2-adrenergic receptors (β2-ARs) through an interaction with the fifth and sixth helices of β2-AR. Coexpression of the two receptors in BE(2)-C neuroblastoma cells potentiates calcium responses to a 6TM-MOR ligand, and this calcium response is completely blocked by a selective β2-antagonist in BE(2)-C cells, and in trigeminal and dorsal root ganglia. Co-administration of 6TM-MOR and β2-AR ligands leads to substantial analgesic synergy and completely reverses opioid-induced hyperalgesia in rodent behavioral models. Together, our results provide evidence that the heterodimerization of 6TM-MOR with β2-AR underlies a molecular mechanism for 6TM cellular signaling, presenting a unique functional responses to opioids. This signaling pathway may contribute to the hyperalgesic effects of opioids that can be efficiently blocked by β2-AR antagonists, providing a new avenue for opioid therapy.}, }
@article {pmid26559654, year = {2016}, author = {Weigele, J and Franz-Odendaal, TA and Hilbig, R}, title = {Not All Inner Ears are the Same: Otolith Matrix Proteins in the Inner Ear of Sub-Adult Cichlid Fish, Oreochromis Mossambicus, Reveal Insights Into the Biomineralization Process.}, journal = {Anatomical record (Hoboken, N.J. : 2007)}, volume = {299}, number = {2}, pages = {234-245}, doi = {10.1002/ar.23289}, pmid = {26559654}, issn = {1932-8494}, mesh = {Animals ; Calcium/metabolism ; Chromatography, Liquid/methods ; Cichlids/growth &amp; development/*metabolism ; Ear, Inner/growth &amp; development/*metabolism ; Extracellular Matrix Proteins/*metabolism ; Fish Proteins/*metabolism ; Larva/growth &amp; development/*metabolism ; Microscopy, Electron, Scanning/methods ; Otolithic Membrane/growth &amp; development/*metabolism ; Spectrometry, Mass, Electrospray Ionization/methods ; Tandem Mass Spectrometry/methods ; }, abstract = {The fish ear stones (otoliths) consist mainly of calcium carbonate and have lower amounts of a proteinous matrix. This matrix consists of macromolecules, which directly control the biomineralization process. We analyzed the composition of this proteinous matrix by mass spectrometry in a shotgun approach. For this purpose, an enhanced protein purification technique was developed that excludes any potential contamination of proteins from body fluids. Using this method we identified eight proteins in the inner ear of Oreochromis mossambicus. These include the common otolith matrix proteins (OMP-1, otolin-1, neuroserpin, SPARC and otoconin), and three proteins (alpha tectorin, otogelin and transferrin) not previously localized to the otoliths. Moreover, we were able to exclude the occurrence of two matrix proteins (starmaker and pre-cerebellin-like protein) known from other fish species. In further analyses, we show that the absence of the OMP starmaker corresponds to calcitic otoliths and that pre-cerebellin-like protein is not present at any stage during the development of the otoliths of the inner ear. This study shows O. mossambicus does not have all of the known otolith proteins indicating that the matrix proteins in the inner ear of fish are not the same across species. Further functional studies of the novel proteins we identified during otolith development are required.}, }
@article {pmid26552354, year = {2015}, author = {Arrabal-Polo, MA and Cano-Garcia, Mdel C and Arrabal-Martin, M}, title = {Lithogenic activity as a factor to consider in the metabolic evaluation of patients with calcium lithiasis.}, journal = {Iranian journal of kidney diseases}, volume = {9}, number = {6}, pages = {469-471}, pmid = {26552354}, issn = {1735-8604}, mesh = {Adult ; Calcium/*metabolism ; Chlorides/blood ; Citrates/urine ; Creatinine/blood/urine ; Fasting ; Female ; Humans ; Hypercalciuria/complications/urine ; Hyperoxaluria/complications/urine ; Kidney Calculi/complications/*metabolism ; Male ; Middle Aged ; Recurrence ; Severity of Illness Index ; Uric Acid/blood/urine ; }, abstract = {Metabolic evaluation is important in high-risk patients with a history of urinary calculi, in order to prevent recurrence. This study aimed to compare patients with calcium calculi and mild lithogenic activity with those with moderate to severe lithogenic activity. Patients with moderate to severe activity had higher levels of urinary calcium level (271.9 mg/24h versus 172.1 mg/24 h, P < .001), uric acid (612.3 mg/24 h versus 528.9 mg/24h, P = .008), and fasting calcium-creatinine ratio (0.16 versus 0.12, P = .001) compared to those with mild lithogenic activity. No association was observed between lithogenic factors in 24-hour urine and mild lithogenic activity in multivariable analysis. We initially thought that in patients who develop recurrent calculi after 5 years or who have mild lithogenic activity, complete metabolic evaluation would not be necessary. However, based on our study findings, it may be important to conduct further studies assessing the lithogenic activity.}, }
@article {pmid26546857, year = {2015}, author = {Dean, MN and Ekstrom, L and Monsonego-Ornan, E and Ballantyne, J and Witten, PE and Riley, C and Habraken, W and Omelon, S}, title = {Mineral homeostasis and regulation of mineralization processes in the skeletons of sharks, rays and relatives (Elasmobranchii).}, journal = {Seminars in cell &amp; developmental biology}, volume = {46}, number = {}, pages = {51-67}, doi = {10.1016/j.semcdb.2015.10.022}, pmid = {26546857}, issn = {1096-3634}, mesh = {Animals ; Bicarbonates/metabolism ; Calcium/metabolism ; Cartilage/*metabolism ; Elasmobranchii/classification/*metabolism ; *Homeostasis ; Minerals/*metabolism ; Phosphates/metabolism ; Sharks/*metabolism ; Skates, Fish/*metabolism ; }, abstract = {Sharks, rays and other elasmobranch fishes are characterized by a skeletal type that is unique among living vertebrates, comprised predominantly of an unmineralized cartilage, covered by a thin outer layer of sub-millimeter, mineralized tiles called tesserae. The mineralized portion of the skeleton appears to grow only by apposition, adding material at the edges of each tessera; maintenance of non-mineralized joints between tesserae is therefore vital, with precise control of mineral deposition and inhibition at the many thousands of growth fronts in the skeleton. Yet, we have only scattered evidence as to how the elasmobranchs mineralize and grow their skeletons. In this review, we take an "environment to skeleton" approach, drawing together research from a vast range of perspectives to track calcium and phosphate from the typical elasmobranch habitats into and through the body, to their deposition at tesseral growth fronts. In the process, we discuss the available evidence for skeletal resorption capability, mineral homeostasis hormones, and nucleation inhibition mechanisms. We also outline relevant theories in crystal nucleation and typical errors in measurements of serum calcium and phosphate in the study of vertebrate biology. We assemble research that suggests consensus in some concepts in elasmobranch skeletal development, but also highlight the very large gaps in our knowledge, particularly in regards to endocrine functional networks and biomineralization mechanisms. In this way, we lay out frameworks for future directions in the study of elasmobranch skeletal biology with stronger and more comparative links to research in other disciplines and into other taxa.}, }
@article {pmid26332888, year = {2015}, author = {Ketha, H and Singh, RJ and Grebe, SK and Bergstralh, EJ and Rule, AD and Lieske, JC and Kumar, R}, title = {Altered Calcium and Vitamin D Homeostasis in First-Time Calcium Kidney Stone-Formers.}, journal = {PloS one}, volume = {10}, number = {9}, pages = {e0137350}, pmid = {26332888}, issn = {1932-6203}, support = {R21 AR058003/AR/NIAMS NIH HHS/United States ; R21-AR060869/AR/NIAMS NIH HHS/United States ; T32 DK007013/DK/NIDDK NIH HHS/United States ; R21 AR060869/AR/NIAMS NIH HHS/United States ; U54DK083908/DK/NIDDK NIH HHS/United States ; P50 DK083007/DK/NIDDK NIH HHS/United States ; U54 DK100227/DK/NIDDK NIH HHS/United States ; R21-AR058003/AR/NIAMS NIH HHS/United States ; U54 DK083908/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Calcium/*metabolism ; Cohort Studies ; Ergocalciferols/*metabolism ; Female ; Fibroblast Growth Factor-23 ; *Homeostasis ; Humans ; Kidney Calculi/*metabolism ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) concentrations have been reported among cohorts of recurrent calcium (Ca) kidney stone-formers and implicated in the pathogenesis of hypercalciuria. Variations in Ca and vitamin D metabolism, and excretion of urinary solutes among first-time male and female Ca stone-formers in the community, however, have not been defined.<br><br>METHODS: In a 4-year community-based study we measured serum Ca, phosphorus (P), 25-hydroxyvitamin D (25(OH)D), 1,25(OH)2D, 24,25-dihydroxyvitamin D (24,25(OH)2D), parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) concentrations in first-time Ca stone-formers and age- and gender frequency-matched controls.<br><br>RESULTS: Serum Ca and 1,25(OH)2D were increased in Ca stone-formers compared to controls (P = 0.01 and P = 0.001). Stone-formers had a lower serum 24,25(OH)2D/25(OH)D ratio compared to controls (P = 0.008). Serum PTH and FGF-23 concentrations were similar in the groups. Urine Ca excretion was similar in the two groups (P = 0.82). In controls, positive associations between serum 25(OH)D and 24,25(OH)2D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)2D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)2D, were not observed. 1,25(OH)2D concentrations associated more weakly with FGF-23 in SF compared with C (P <0.05).<br><br>CONCLUSIONS: Quantitative differences in serum Ca and 1,25(OH)2D and reductions in 24-hydroxylation of vitamin D metabolites are present in first-time SF and might contribute to first-time stone risk.}, }
@article {pmid26277654, year = {2016}, author = {Medley, P and Bollhöfer, A}, title = {Influence of group II metals on Radium-226 concentration ratios in the native green plum (Buchanania obovata) from the Alligator Rivers Region, Northern Territory, Australia.}, journal = {Journal of environmental radioactivity}, volume = {151 Pt 3}, number = {}, pages = {551-557}, doi = {10.1016/j.jenvrad.2015.07.013}, pmid = {26277654}, issn = {1879-1700}, mesh = {Anacardiaceae/*metabolism ; Barium/metabolism ; Calcium/metabolism ; Metals, Alkaline Earth/*metabolism ; Northern Territory ; Radium/*metabolism ; Soil Pollutants, Radioactive/*metabolism ; Strontium/metabolism ; }, abstract = {In this study, uptake of Ra from soil, and the influence of group II metals on Ra uptake, into the stones and edible flesh of the fruit of the wild green plum, Buchanania obovata, was investigated. Selective extraction of the exchangeable fraction of the soil samples was undertaken but was not shown to more reliably predict Ra uptake than total soil Ra activity concentration. Comparison of the group II metal to Ca ratios (i.e. Sr/Ca, Ba/Ca, Ra/Ca) in the flesh with exchangeable Ca shows that Ca outcompetes group II metals for root uptake and that the uptake pathway discriminated against group II metals relative to ionic radius, with uptake of Ca > Sr > Ba >> Ra. Flesh and stone analysis showed that movement of group II metals to these components of the plant, after root uptake, was strongly related. This supports the hypothesis that Sr, Ba and Ra are being taken up as analogue elements, and follow the same uptake and translocation pathways, with Ca. Comparison with previously reported data from a native passion fruit supports the use of total soil CRs on natural, undisturbed sites. As exchangeable CRs for Ra reach a saturation value it may be possible to make more precise predictions using selective extraction techniques for contaminated or disturbed sites.}, }
@article {pmid26193266, year = {2015}, author = {He, D and Lu, Y and Hu, H and Zhang, J and Qin, B and Wang, Y and Xing, S and Xi, Q and Wang, S}, title = {The Wnt11 Signaling Pathway in Potential Cellular EMT and Osteochondral Differentiation Progression in Nephrolithiasis Formation.}, journal = {International journal of molecular sciences}, volume = {16}, number = {7}, pages = {16313-16329}, pmid = {26193266}, issn = {1422-0067}, mesh = {Animals ; Biomarkers/metabolism ; Blotting, Western ; Calcium/metabolism ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/metabolism ; *Cell Differentiation/drug effects ; Cell Separation ; Cells, Cultured ; Chondrocytes/drug effects/*pathology ; Chondrogenesis/drug effects ; Disease Models, Animal ; Disease Progression ; Epithelial Cells/drug effects/metabolism ; *Epithelial-Mesenchymal Transition/drug effects ; Fluorescent Antibody Technique ; Gene Knockdown Techniques ; Intracellular Space/metabolism ; Kidney Tubules/pathology ; Nephrolithiasis/blood/*metabolism/*pathology ; Nifedipine/pharmacology ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering/metabolism ; Rats ; *Signal Transduction/drug effects ; Transforming Growth Factor beta1/blood/urine ; Wnt Proteins/*metabolism ; }, abstract = {The molecular events leading to nephrolithiasis are extremely complex. Previous studies demonstrated that calcium and transforming growth factor-β1 (TGF-β1) may participate in the pathogenesis of stone formation, but the explicit mechanism has not been defined. Using a self-created genetic hypercalciuric stone-forming (GHS) rat model, we observed that the increased level of serous/uric TGF-β1 and elevated intracellular calcium in primary renal tubular epithelial cells (PRECs) was associated with nephrolithiasis progression in vivo. In the setting of high calcium plus high TGF-β1 in vitro, PRECs showed great potential epithelial to mesenchymal transition (EMT) progression and osteochondral differentiation properties, representing the multifarious increased mesenchymal and osteochondral phenotypes (Zeb1, Snail1, Col2A1, OPN, Sox9, Runx2) and decreased epithelial phenotypes (E-cadherin, CK19) bythe detection of mRNAs and corresponding proteins. Moreover, TGF-β-dependent Wnt11 knockdown and L-type Ca2+ channel blocker could greatly reverse EMT progression and osteochondral differentiation in PRECs. TGF-β1 alone could effectively promote EMT, but it had no effect on osteochondral differentiation in NRK cells (Rat kidney epithelial cell line). Stimulation with Ca2+ alone did not accelerate differentiation of NRK. Co-incubation of extracellular Ca2+ and TGF-β1 synergistically promotes EMT and osteochondral differentiation in NRK control cells. Our data supplied a novel view that the pathogenesis of calcium stone development may be associated with synergic effects of TGF-β1 and Ca2+, which promote EMT and osteochondral differentiation via Wnt11 and the L-type calcium channel.}, }
@article {pmid26150027, year = {2015}, author = {Prezioso, D and Strazzullo, P and Lotti, T and Bianchi, G and Borghi, L and Caione, P and Carini, M and Caudarella, R and Ferraro, M and Gambaro, G and Gelosa, M and Guttilla, A and Illiano, E and Martino, M and Meschi, T and Messa, P and Miano, R and Napodano, G and Nouvenne, A and Rendina, D and Rocco, F and Rosa, M and Sanseverino, R and Salerno, A and Spatafora, S and Tasca, A and Ticinesi, A and Travaglini, F and Trinchieri, A and Vespasiani, G and Zattoni, F and , }, title = {Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.}, journal = {Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica}, volume = {87}, number = {2}, pages = {105-120}, doi = {10.4081/aiua.2015.2.105}, pmid = {26150027}, issn = {1124-3562}, mesh = {Adult ; Aged ; Calcium Oxalate/metabolism/urine ; Calcium, Dietary/*administration &amp; dosage ; Child ; Citric Acid/metabolism ; Dietary Proteins/*administration &amp; dosage ; Dietary Supplements ; Drinking Water/*administration &amp; dosage ; Evidence-Based Medicine ; Humans ; Kidney Calculi/*diet therapy/etiology/metabolism/*prevention &amp; control/urine ; Nephrology ; Patient Education as Topic ; Risk Factors ; Societies, Medical ; Sodium, Dietary/*administration &amp; dosage ; Treatment Outcome ; }, abstract = {OBJECTIVE: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease.<br><br>MATERIALS AND METHODS: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed.<br><br>RESULTS: Evidence from the selected studies were used to form evidence-based guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions.<br><br>CONCLUSIONS: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. HYPERCALCIURIA: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content &#x2265; 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. HYPEROXALURIA: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. HYPERURICOSURIA: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. HYPOCITRATURIA: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels.<br><br>CHILDREN: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (< 20 g/day) low-salt (< 2 g/day) diet with high hydration (> 3 liters/day) is strongly advised in children with cystinuria. ELDERLY: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.}, }
@article {pmid26116865, year = {2015}, author = {Fowler, ED and Benoist, D and Drinkhill, MJ and Stones, R and Helmes, M and Wüst, RC and Stienen, GJ and Steele, DS and White, E}, title = {Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension.}, journal = {Journal of molecular and cellular cardiology}, volume = {86}, number = {}, pages = {1-8}, pmid = {26116865}, issn = {1095-8584}, support = {PG/13/3/29924/BHF_/British Heart Foundation/United Kingdom ; RG/11/10/28924/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Calcium/metabolism ; Creatine Kinase/biosynthesis/*metabolism ; Diastole ; Heart Failure/*enzymology/pathology ; Humans ; Hypertension, Pulmonary/*enzymology/pathology ; Myocardium/enzymology/pathology ; Myocytes, Cardiac/enzymology/pathology ; Pulmonary Artery/enzymology/pathology ; Rats ; Sarcomeres/enzymology/pathology ; Ventricular Dysfunction, Right/*enzymology/pathology ; }, abstract = {Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control animals. In vivo right ventricular diastolic pressure-volume relationships were measured in anesthetized animals; diastolic force-length relationships in single enzymatically dissociated myocytes and myocardial creatine kinase levels by Western blot. We observed diastolic dysfunction in right ventricular failure indicated by significantly steeper diastolic pressure-volume relationships in vivo and diastolic force-length relationships in single myocytes. There was a significant reduction in creatine kinase protein expression in failing right ventricle. Dysfunction also manifested as a shorter diastolic sarcomere length in failing myocytes. This was associated with a Ca(2+)-independent mechanism that was sensitive to cross-bridge cycling inhibition. In saponin-skinned failing myocytes, addition of exogenous creatine kinase significantly lengthened sarcomeres, while in intact healthy myocytes, inhibition of creatine kinase significantly shortened sarcomeres. Creatine kinase inhibition also changed the relatively flat contraction amplitude-stimulation frequency relationship of healthy myocytes into a steeply negative, failing phenotype. Decreased creatine kinase expression leads to diastolic dysfunction. We propose that this is via local reduction in ATP:ADP ratio and thus to Ca(2+)-independent force production and diastolic sarcomere shortening. Creatine kinase inhibition also mimics a definitive characteristic of heart failure, the inability to respond to increased demand. Novel therapies for pulmonary artery hypertension are needed. Our data suggest that cardiac energetics would be a potential ventricular therapeutic target.}, }
@article {pmid26099826, year = {2015}, author = {Tolentino, TA and Bertoli, AC and dos Santos Pires, M and Carvalho, R and Labory, CR and Nunes, JS and Bastos, AR and de Freitas, MP}, title = {Applications in environmental bioinorganic: Nutritional and ultrastructural evaluation and calculus of thermodynamic and structural properties of metal-oxalate complexes.}, journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy}, volume = {150}, number = {}, pages = {750-757}, doi = {10.1016/j.saa.2015.06.016}, pmid = {26099826}, issn = {1873-3557}, mesh = {Brachiaria/*metabolism/*ultrastructure ; Calcium/*metabolism ; Coordination Complexes/*metabolism ; Lead/*metabolism/toxicity ; Models, Molecular ; Oxalates/*metabolism ; Plant Leaves/metabolism/ultrastructure ; Plant Roots/metabolism/ultrastructure ; Thermodynamics ; }, abstract = {Lead (Pb) is known by its toxicity both for animals and plants. In order to evaluate its toxicity, plants of Brachiaria brizantha were cultivated on nutritive solution of Hoagland during 90 days and submitted to different concentrations of Pb. The content of macro and micronutrients was evaluated and there was a reduction on root content of Ca, besides the lowest dosages of Pb had induced an increase of N, S, Mn, Cu, Zn and Fe. The cell ultrastructure of leaves and roots were analyzed by transmission electronic microscopy (TEM). Among the main alterations occurred there were invaginations on cell walls, the presence of crystals on the root cells, accumulation of material on the interior of cells and vacuolar compartmentalization. On the leaves the degradation of chloroplasts was observed, as well as the increase of vacuoles. Structures for the formation of oxalate crystals were proposed through molecular modeling and thermodynamic stability. Calculi suggest the formation of highly stable metal-oxalate complexes.}, }
@article {pmid26097993, year = {2015}, author = {Shah, AD and Hsiao, EC and O'Donnell, B and Salmeen, K and Nussbaum, R and Krebs, M and Baumgartner-Parzer, S and Kaufmann, M and Jones, G and Bikle, DD and Wang, Y and Mathew, AS and Shoback, D and Block-Kurbisch, I}, title = {Maternal Hypercalcemia Due to Failure of 1,25-Dihydroxyvitamin-D3 Catabolism in a Patient With CYP24A1 Mutations.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {100}, number = {8}, pages = {2832-2836}, pmid = {26097993}, issn = {1945-7197}, support = {R01AR055588/AR/NIAMS NIH HHS/United States ; R01 AR050023/AR/NIAMS NIH HHS/United States ; T32 DK007418/DK/NIDDK NIH HHS/United States ; R01AR055924/AR/NIAMS NIH HHS/United States ; U41 HG006834/HG/NHGRI NIH HHS/United States ; IP1 BX001599/BX/BLRD VA/United States ; U41 HG006834-01A1/HG/NHGRI NIH HHS/United States ; U19 HD077627/HD/NICHD NIH HHS/United States ; I01 BX001066/BX/BLRD VA/United States ; R01 AR055588/AR/NIAMS NIH HHS/United States ; R01 AR055924/AR/NIAMS NIH HHS/United States ; 1U19HD077627-01/HD/NICHD NIH HHS/United States ; R01 DK054793/DK/NIDDK NIH HHS/United States ; I01 BX003814/BX/BLRD VA/United States ; 5T32DK007418-34/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Hypercalcemia/*genetics/metabolism ; Metabolic Networks and Pathways/genetics ; *Mutation ; Nephrolithiasis/genetics/metabolism ; Pregnancy ; Pregnancy Complications/*genetics/metabolism ; Vitamin D/*analogs &amp; derivatives/metabolism ; Vitamin D3 24-Hydroxylase/*genetics ; }, abstract = {CONTEXT: Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis.<br><br>CASE: A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1.<br><br>CONCLUSIONS: This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated.}, }
@article {pmid26089600, year = {2015}, author = {Khaleel, A and Wu, MS and Wong, HS and Hsu, YW and Chou, YH and Chen, HY}, title = {A Single Nucleotide Polymorphism (rs4236480) in TRPV5 Calcium Channel Gene Is Associated with Stone Multiplicity in Calcium Nephrolithiasis Patients.}, journal = {Mediators of inflammation}, volume = {2015}, number = {}, pages = {375427}, pmid = {26089600}, issn = {1466-1861}, mesh = {Adult ; Calcium/*metabolism ; Female ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Male ; Middle Aged ; Nephrolithiasis/*genetics/pathology ; Polymorphism, Single Nucleotide/*genetics ; TRPV Cation Channels/*genetics ; }, abstract = {Nephrolithiasis is characterized by calcification of stones in the kidneys from an unknown cause. Animal models demonstrated the functional roles of the transient receptor potential vanilloid member 5 (TRPV5) gene in calcium renal reabsorption and hypercalciuria. Therefore, TRPV5 was suggested to be involved in calcium homeostasis. However, whether genetic polymorphisms of TRPV5 are associated with kidney stone multiplicity or recurrence is unclear. In this study, 365 Taiwanese kidney-stone patients were recruited. Both biochemical data and DNA samples were collected. Genotyping was performed by a TaqMan allelic discrimination assay. We found that a TRPV5 polymorphism (rs4236480) was observed to be associated with stone multiplicity of calcium nephrolithiasis, as the risk of stone multiplicity was higher in patients with the TT+CT genotype than in patients with the CC genotype (p = 0.0271). In summary, despite the complexity of nephrolithiasis and the potential association of numerous calcium homeostatic absorption/reabsorption factors, TRPV5 plays an important role in the pathogenesis of calcium nephrolithiasis.}, }
@article {pmid26085877, year = {2015}, author = {Rull, MA and Cano-García, Mdel C and Arrabal-Martín, M and Arrabal-Polo, MA}, title = {The importance of urinary calcium in postmenopausal women with osteoporotic fracture.}, journal = {Canadian Urological Association journal = Journal de l'Association des urologues du Canada}, volume = {9}, number = {3-4}, pages = {E183-6}, pmid = {26085877}, issn = {1911-6470}, abstract = {INTRODUCTION: Calcium stones are associated with osteoporosis and manifested mainly by elevated fasting urinary calcium/creatinine ratio. The objective of this study is to demonstrate the presence of abnormal metabolism of calcium and calciuria in women with osteoporotic fracture with no previously known renal lithiasis compared to women without osteoporosis and without renal lithiasis.<br><br>METHODS: In total, 87 women were included in the study. They were divided into two groups: Group 1 with 55 postmenopausal women with osteoporotic fracture and without renal lithiasis; and Group 2 with 32 postmenopausal women without osteoporosis and without history of renal lithiasis. The following parameters of phospho-calcium metabolism were analyzed: calciuria 24-hour, oxaluria 24-hour, uricosuria 24-hour, and citraturia 24-hour. The presence of hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia was compared between groups. Statistical significance was set at p &#x2264; 0.05.<br><br>RESULTS: The mean age was 70.1 &#xb1; 13.8 in Group 1 and 56.7 &#xb1; 6.4 in Group 2 (p = 0.0001). Women in Group 1 had higher levels of serum alkaline phosphatase (p < 0.05) and fasting urinary calcium/creatinine ratio (p < 0.05). The percentage of patients with hypercalciuria in Group 1 (40%) was higher compared to Group 2 (18.8%) and statistically significant (p = 0.04). There were no statistically significant differences in the percentage of hyperoxaluria, hyperuricosuria, and hypocitraturia between groups. This study has its limitations including its cross-sectional nature at a unique centre and its low number of patients.<br><br>CONCLUSION: The determination of urinary calcium and fasting calcium/creatinine ratio in postmenopausal women with osteoporotic fracture without renal lithiasis may facilitate individualization of medical therapy and decreasing lithogenic risk.}, }
@article {pmid26033763, year = {2015}, author = {Ubetagoyena Arrieta, M and Corera Casty, MN and Martínez Saenz de Jubera, J and González Hospitaler, MT and Areses Trapote, R and Pérez-Yarza, EG}, title = {[Risk assessment in children with lithogenic kidney stones].}, journal = {Archivos espanoles de urologia}, volume = {68}, number = {4}, pages = {429-434}, pmid = {26033763}, issn = {0004-0614}, mesh = {Child ; Female ; Humans ; Kidney Calculi/chemistry/*epidemiology ; Male ; Retrospective Studies ; Risk Assessment ; Risk Factors ; }, abstract = {OBJECTIVE: The aim of this study was to describe the lithogenic risk profile of pediatric patients with lithiasis.<br><br>METHODS: We retrospectively analyzed the metabolic studies in 24-hour urine samples in 47 pediatric patients with lithiasis. Biochemical determinations were made in blood and 24-hour urine. Oxalate calcium, brushite, struvite and uric acid salt saturations were calculated. 49 healthy children were used as a control group.<br><br>RESULTS: No significant differences were found in biochemical blood parameters between children with stones and the group without stones. Calciuria, uricosuria and phosphaturia, oxalate calcium, brushite and uric acid saturations were higher in lithiasic children. In the multivariate analysis, using a logistic regression model, we only found hypercalciuria as lithogenic risk factor. (OR = 1.96 p <0.002).<br><br>CONCLUSIONS: Urinary metabolic abnormalities and elevated salt saturations in urine are a frequent finding in children with urolithiasis, but in our study we only found hypercalciuria as an independent risk factor for the formation of lithiasis.}, }
@article {pmid25962642, year = {2015}, author = {Johnston, H and Brown, DM and Kanase, N and Euston, M and Gaiser, BK and Robb, CT and Dyrynda, E and Rossi, AG and Brown, ER and Stone, V}, title = {Mechanism of neutrophil activation and toxicity elicited by engineered nanomaterials.}, journal = {Toxicology in vitro : an international journal published in association with BIBRA}, volume = {29}, number = {5}, pages = {1172-1184}, doi = {10.1016/j.tiv.2015.04.021}, pmid = {25962642}, issn = {1879-3177}, support = {G0601481/MRC_/Medical Research Council/United Kingdom ; MR/K013386/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Calcium/metabolism ; Cell Survival/drug effects ; Cytokines/metabolism ; HL-60 Cells ; Humans ; Nanostructures/*toxicity ; Nanotubes, Carbon/toxicity ; Neutrophil Activation/*drug effects ; Silver/toxicity ; Soot/toxicity ; Superoxides/metabolism ; Titanium/toxicity ; Zinc Oxide/toxicity ; }, abstract = {The effects of nanomaterials (NMs) on biological systems, especially their ability to stimulate inflammatory responses requires urgent investigation. We evaluated the response of the human differentiated HL60 neutrophil-like cell line to NMs. It was hypothesised that NM physico-chemical characteristics would influence cell responsiveness by altering intracellular Ca2+ concentration [Ca2+]i and reactive oxygen species production. Cells were exposed (1.95-125 μg/ml, 24 h) to silver (Ag), zinc oxide (ZnO), titanium dioxide (TiO2), multi-walled carbon nanotubes (MWCNTs) or ultrafine carbon black (ufCB) and cytotoxicity assessed (alamar blue assay). Relatively low (TiO2, MWCNTs, ufCB) or high (Ag, ZnO) cytotoxicity NMs were identified. Sub-lethal impacts of NMs on cell function were investigated for selected NMs only, namely TiO2, Ag and ufCB. Only Ag stimulated cell activation. Within minutes, Ag stimulated an increase in [Ca2+]i (in Fura-2 loaded cells), and a prominent inward ion current (assessed by electrophysiology). Within 2-4 h, Ag increased superoxide anion release and stimulated cytokine production (MCP-1, IL-8) that was diminished by Ca2+ inhibitors or trolox. Light microscopy demonstrated that cells had an activated phenotype. In conclusion NM toxicity was ranked; Ag>ufCB>TiO2, and the battery of tests used provided insight into the mechanism of action of NM toxicity to guide future testing strategies.}, }
@article {pmid25955223, year = {2015}, author = {Palmieri, S and Eller-Vainicher, C and Cairoli, E and Morelli, V and Zhukouskaya, VV and Verga, U and Filopanti, M and Vicentini, L and Ferrero, S and Spada, A and Chiodini, I}, title = {Hypercalciuria May Persist After Successful Parathyroid Surgery and It Is Associated With Parathyroid Hyperplasia.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {100}, number = {7}, pages = {2734-2742}, doi = {10.1210/jc.2014-4548}, pmid = {25955223}, issn = {1945-7197}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Hypercalciuria/*epidemiology ; Hyperparathyroidism, Primary/*epidemiology/*surgery ; Hyperplasia/epidemiology ; Longitudinal Studies ; Male ; Middle Aged ; Parathyroid Glands/*pathology/surgery ; Parathyroidectomy/*statistics &amp; numerical data ; Postoperative Period ; Prevalence ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {CONTEXT: Hypercalciuria is frequently found in primary hyperparathyroidism (1HPT) and, although it generally normalizes after successful parathyroidectomy, may persist in some patients. The factors associated with persistent calcium renal leak (cRL) have not been clarified.<br><br>OBJECTIVE: The purpose of this study was to determine the prevalence of cRL in our 1HPT population and investigate cRL-related factors.<br><br>DESIGN: This was a retrospective longitudinal study.<br><br>SETTING: The study was conducted in an outpatient setting.<br><br>PATIENTS/INTERVENTION: The participants were 95 patients with 1HPT successfully operated on who had a normal estimated glomerular filtration rate.<br><br>MAIN OUTCOME MEASURES: The biochemical parameters of calcium metabolism and bone mineral density (BMD) measured by dual-X-ray absorptiometry before and 24 months after surgery were assessed. All histological findings were recorded.<br><br>RESULTS: The prevalence of hypercalciuria before and after surgery was 74% and 32%, respectively. Before, surgery patients with cRL showed lower calcium and higher phosphate levels than those without cRL (10.9 &#xb1; 0.6 vs 11.4 &#xb1; 0.8 mg/dL [2.7 &#xb1; 0.2 vs 2.8 &#xb1; 0.2 mmol/L], P = .01 and 2.6 &#xb1; 0.5 vs 2.4 &#xb1; 0.4 mg/dL [0.84 &#xb1; 0.2 vs 0.77 &#xb1; 0.1 mmol/L], P = .04, respectively), whereas 24-h calciuria levels and the prevalence of 1HPT complications (osteoporosis, renal stones, and hypertension) were comparable. After surgery, serum calcium, phosphate, and PTH levels were comparable between patients with and without cRL. The prevalence of the histological finding of parathyroid hyperplasia was higher in patients with cRL (50%) than in patients without cRL (22%) (P = .01). The presence of cRL was independently associated with presurgery hypercalciuria (odds ratio, 4.71; 95% confidence interval, 1.18-18.8; P = .03) and parathyroid hyperplasia (odds ratio, 3.52; 95% confidence interval, 1.31-9.43; P = .01). Only patients without cRL had improved BMD at the spine (P = .04), total femur (P = .01), and femoral neck (P = .01).<br><br>CONCLUSIONS: cRL is present in 30% of patients with 1HPT after successful surgery, and it is associated with parathyroid hyperplasia before surgery and the lack of improvement in BMD after surgery.}, }
@article {pmid25944923, year = {2015}, author = {Giardini, JL and Yan, ND and Heyland, A}, title = {Consequences of calcium decline on the embryogenesis and life history of Daphnia magna.}, journal = {The Journal of experimental biology}, volume = {218}, number = {Pt 13}, pages = {2005-2014}, doi = {10.1242/jeb.123513}, pmid = {25944923}, issn = {1477-9145}, mesh = {Animals ; Body Size ; Calcium/analysis/*metabolism ; Daphnia/*embryology/physiology ; Embryo, Nonmammalian ; Female ; Fresh Water/chemistry ; Life Cycle Stages ; Molting ; Reproduction/physiology ; }, abstract = {Ambient calcium is declining in thousands of soft-water lake habitats in temperate regions as a consequence of unsustainable forestry practices, decreased atmospheric calcium deposition and acidic deposition. As their exoskeleton is heavily reinforced with calcium, freshwater crustaceans have a high specific calcium requirement relative to other aquatic organisms. Daphnia, in particular, is an ideal crustacean for investigating the consequences of calcium decline because it is an abundant and important member of freshwater zooplankton communities. Although it has been established that adult and juvenile Daphnia have different tolerances to low ambient calcium as a result of their different life stage-specific calcium requirements, the consequences of declining calcium on embryonic development have never been investigated. Here, we describe the distribution of calcium in embryonic stages of D. magna and introduce a novel and easy to use staging scheme. We tested whether calcium can be traced from mothers to their offspring. Finally, we assessed the fitness consequences of maternal provisioning in limiting calcium environments. We found that while embryos require calcium for their development and moulting, they do not equilibrate with environmental calcium levels. Instead, we were able to trace calcium from mothers to their offspring. Furthermore, our data strongly suggest that females are faced with an allocation trade-off between providing calcium to their offspring and using it for growth and moulting. Together, these data provide novel insights into the consequences of calcium decline for freshwater zooplankton.}, }
@article {pmid25823394, year = {2015}, author = {Jia, Z and Wang, S and He, D and Cui, L and Lu, Y and Hu, H and Qin, B and Zhao, Z}, title = {Role of calcium in the regulation of bone morphogenetic protein 2, runt-related transcription factor 2 and Osterix in primary renal tubular epithelial cells by the vitamin D receptor.}, journal = {Molecular medicine reports}, volume = {12}, number = {2}, pages = {2082-2088}, doi = {10.3892/mmr.2015.3568}, pmid = {25823394}, issn = {1791-3004}, mesh = {Animals ; Bone Morphogenetic Protein 2/genetics/*metabolism ; Calcium/*metabolism ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/genetics/*metabolism ; Epithelial Cells/cytology/metabolism ; Female ; Gene Expression Regulation ; Gene Knockdown Techniques ; Kidney Tubules/*cytology/metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitriol/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {The aim of the present study was to investigate the effect of 1,25(OH)2D3/vitamin D receptor (VDR) and calcium on the expression levels of osteogenic factors in primary renal tubular epithelial cells (RTECs) using genetic hypercalciuric rats. The basal levels of osteogenic factors were detected in Sprague Dawley and genetic hypercalciuric rats. The gene and protein levels of bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2) and osterix were detected in the RTECs transduced with Lenti-VDR-sh and were incubated with calcium. Using the o-cresolphthalein complexone method, the calcium levels of the primary RTECs cultured with Lenti-VDR-sh and with 1,25(OH)2D3 were assessed. The basal levels of BMP2, Runx2 and Osterix in the cells were significantly higher in the genetic hypercalciuric rats compared with the control rats. VDR knockdown in the RTECs reduced the expression levels of BMP2, Runx2 and Osterix. The calcium depositions in the primary RTECs were also decreased following exposure to Lenti-VDR-sh, but increased following treatment with 1,25(OH)2D3. The expression levels of BMP2, Runx2 and Osterix were markedly increased in the cells incubated with calcium compared with the cells treated with normal saline and the untreated cells. These findings indicated that osteogenic factors, including BMP2, Runx2 and Osterix may be important in renal stone formation in idiopathic hypercalciuria. VDR may mediate the increased expression levels of BMP2, Runx2 and Osterix by positively regulating calcium levels in primary RTECs.}, }
@article {pmid25807757, year = {2014}, author = {Aliaev, IuG and Egshatian, LV and Rapoport, LM and Lartsova, EV}, title = {[Hormonal and metabolic disorders as systemic factor for the formation of urinary calculi].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {5}, pages = {35-39}, pmid = {25807757}, issn = {1728-2985}, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Glucose/metabolism ; Calcium/blood/*metabolism/urine ; Carbohydrate Metabolism ; Dyslipidemias/blood/complications/*metabolism/urine ; Female ; Humans ; Hyperparathyroidism/blood/complications/*metabolism/urine ; Lipid Metabolism ; Magnesium/metabolism ; Male ; Middle Aged ; Phosphorus/blood/*metabolism/urine ; Purines/metabolism ; Urinary Calculi/blood/*etiology/*metabolism/urine ; }, abstract = {In patients suffering from urolithiasis, metabolic diagnostics often reveals abnormalities contributing to the formation of stones: hypocitraturia, hyper- and hypocalcemia, hypercalciuria, hypomagnesemia/hypomagnesuria, hyperoxalaturia, etc. Before surgery, complex biochemical examination of blood and 24-hourcollection urine in 82 patients with urolithiasis was performed. The analysis of the main laboratory parameters of carbohydrate, lipid, calcium and phosphorus and purine metabolism found the prevalence of violations of calcium and phosphorus metabolism in these patients. Dyslipidemia was diagnosed in 31 (37.8%) patients. There was a significant positive correlation between serum total cholesterol and serum total calcium (rs = 0.3315, P = 0.0103). Low serum calcium levels were associated with hyperoxalaturia (rs = -0.4270, P = 0.0295). There was a significant effect of natriuria on urinary excretion of oxalate (rs = 0.6107, P = 0.0001), Mg (rs = 0.4156, P = 0.0096) and K (rs = 0.5234, P = 0.00005). The study shows the role of magnesium in the prevention of recurrence and manifestation of urolithiasis. The combination of two or more types of hormonal and metabolic disorders increases the incidence of recurrent stones. Timely correction of hormonal-metabolic status allows to reduce the risk of stone formation, and hospitalization attributable to the complications associated.}, }
@article {pmid25733263, year = {2015}, author = {Hartman, C and Friedlander, JI and Moreira, DM and Leavitt, DA and Hoenig, DM and Smith, AD and Okeke, Z}, title = {Does hypertension impact 24-hour urine parameters in patients with nephrolithiasis?.}, journal = {Urology}, volume = {85}, number = {3}, pages = {539-543}, doi = {10.1016/j.urology.2014.12.013}, pmid = {25733263}, issn = {1527-9995}, mesh = {*Circadian Rhythm ; Female ; Humans ; Hypertension/*complications/*urine ; Kidney Calculi/chemistry/*complications/*urine ; Male ; Middle Aged ; Multivariate Analysis ; Nephrolithiasis/complications/urine ; Retrospective Studies ; }, abstract = {OBJECTIVE: To examine the differences in 24-hour urine parameters and stone composition between patients with and without systemic hypertension (HTN) in a large cohort of stone formers.<br><br>MATERIALS AND METHODS: We performed a retrospective review over a 10-year period of patients with stone, who had completed a 24-hour urinalysis (Litholink) and for whom demographic information was available, including the presence of HTN. Univariate and multivariate analyses were performed, comparing the 24-hour urinalysis profiles of patients with HTN with that of normotensive patients.<br><br>RESULTS: Of the 1115 patients eligible for inclusion, 442 patients (40%) had HTN and 673 (60%) did not. Patients with HTN were significantly older, had a higher body mass index, and had a greater number of comorbid conditions than normotensive patients. Univariate analysis revealed significantly lower urine pH, calcium, supersaturation (SS) of calcium oxalate (CaOx) and SS calcium phosphate (all P&#xa0;<.05) in patients with HTN. Multivariate analysis showed significantly lower calcium, citrate, and SS CaOx in patients with HTN (all P&#xa0;<.05).<br><br>CONCLUSION: Our results demonstrate lower levels of calcium and SS CaOx on univariate and multivariate analysis, as well as lower levels of citrate on multivariate analysis in patients with HTN. These results suggest that lower levels of citrate may contribute to stone formation to a greater degree in patients with HTN than abnormalities in calcium metabolism.}, }
@article {pmid25709002, year = {2015}, author = {Ochoa-Hortal Rull, M&#xc1; and Cano-García, MC and Arrabal Martín, M and Cano Gea, R and Reyes García, R and Arrabal-Polo, MA}, title = {Calcium and phosphorus metabolism and lithogenic factors in patients with osteoporotic fracture.}, journal = {Actas urologicas espanolas}, volume = {39}, number = {5}, pages = {279-282}, doi = {10.1016/j.acuro.2014.12.004}, pmid = {25709002}, issn = {1699-7980}, mesh = {Aged ; Aged, 80 and over ; Alkaline Phosphatase/urine ; Calcium/*metabolism ; Citric Acid/urine ; Fasting/urine ; Female ; Humans ; Hypercalciuria/*etiology ; Male ; Middle Aged ; Osteoporosis/complications/*metabolism ; Osteoporotic Fractures/etiology/surgery/*urine ; Parathyroid Hormone/urine ; Phosphorus/*metabolism ; Risk Factors ; Uric Acid/urine ; Urolithiasis/*etiology ; Vitamin D/analogs &amp; derivatives/urine ; }, abstract = {OBJECTIVES: To demonstrate the attendance of mineral metabolism disorders and lithogenic factors in patients' urine with osteoporotic fracture without previously known stones<br><br>MATERIAL AND METHODS: 67 patients with osteoporotic fractures surgically treated in trauma service are included. The area of the fracture site, fracture mechanism and the presence of osteoporosis were the factors taken into account to diagnose osteoporotic fracture. Mineral metabolism, calciuria, oxaluria, uricosuria and citraturia in 24hours urine were analyzed. The presence of abnormal calcium and phosphorus metabolism was proved comparing hypercalciuria patients with normocalciuria ones.<br><br>RESULTS: 12 men and 55 women with mean age 68.8&#xb1;14.5 years old were included. Mean Body Mass Index (BMI) was 27.4&#xb1;4.1kg/m2. 42% of patients showed hypercalciuria, 34% hyperoxaluria, 34% hypocitraturia and 7% hyperuricosuria. Statistically significant differences were observed only in fasting calcium/creatinine ratio (0.17 vs. 0.08; P<.0001) when comparing patients with hypercalciuria with those with normocalciuria.<br><br>CONCLUSIONS: Patients with osteoporotic fractures show different lithogenic factors in urine, mainly hypercalciuria, always in fasting conditions.}, }
@article {pmid25652872, year = {2015}, author = {Arrabal-Martin, M and Poyatos-Andujar, A and Cano-García, Mdel C and Quesada-Charneco, M and Abad-Menor, F and Girón Prieto, MS and de Haro Muñoz, T and Arrabal-Polo, MA}, title = {The importance of calciuria as lithogenic factors in patients with osteopenia/osteoporosis.}, journal = {International urology and nephrology}, volume = {47}, number = {3}, pages = {445-449}, pmid = {25652872}, issn = {1573-2584}, mesh = {Adult ; Age Factors ; Alkaline Phosphatase/urine ; Bone Density ; Bone Diseases, Metabolic/complications/urine ; Calcium/urine ; Case-Control Studies ; Collagen/urine ; Cross-Sectional Studies ; Female ; Humans ; Hypercalciuria/complications/*urine ; Kidney Calculi/*etiology/*urine ; Male ; Middle Aged ; Osteoporosis/complications/*urine ; Oxalic Acid/urine ; Parathyroid Hormone/urine ; Peptide Fragments/urine ; Phosphorus/urine ; Recurrence ; Uric Acid/urine ; }, abstract = {PURPOSE: Recurrent kidney stones are associated with bone mineral density loss, altered bone remodeling markers, hypercalciuria and increased in fasting calcium/creatinine ratio. The objective was to determine biochemical alterations in urine in patients with osteopenia/osteoporosis without calcium kidney stones compared with patients with calcium kidney stones.<br><br>METHODS: This is a cross-sectional study including 142 patients who were divided in two groups: Group 1 (patients with recurrent calcium kidney stones) and Group 2 (patients with osteopenia/osteoporosis in the lumbar spine or hip). Analyses of bone mineral density, calcium-phosphorous and bone metabolism and lithogenic risk factors in fasting urine samples and 24-h urine samples were performed. Statistical analysis was carried out with SPSS 17.0. A p&#xa0;&#x2264;&#xa0;0.05 was considered statistically significant.<br><br>RESULTS: Patients in Group 2 presented greater loss of bone mineral density and more elevated alkaline phosphatase, iPTH, phosphorous and &#x3b2;-crosslaps levels, as compared to patients in Group 1. However, Group 1 presented greater urine calcium, oxalate and uric acid and a higher proportion of hypocitraturia, hypercalciuria and hyperoxaluria, as compared to Group 2. Multivariate analysis revealed that advanced age and &#x3b2;-crosslaps levels are risk factors for bone mineral density loss, while low urinary calcium excretion was protective against bone demineralization.<br><br>CONCLUSION: Patients with osteopenia/osteoporosis without lithiasis present some urinary biochemical alterations. This would explain the lack of lithogenic activity, although low calcium excretion in 24-h urine samples is a protective factor against the loss of bone mineral density.}, }
@article {pmid25568567, year = {2014}, author = {Bijelic, R and Milicevic, S and Balaban, J}, title = {Incidence of osteoporosis in patients with urolithiasis.}, journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)}, volume = {68}, number = {5}, pages = {335-338}, pmid = {25568567}, issn = {0350-199X}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bone Density ; Calcium/*metabolism ; Female ; Humans ; Incidence ; Kidney Calculi/*etiology/*physiopathology ; Male ; Middle Aged ; Osteoporosis/epidemiology/*etiology ; Prospective Studies ; Urolithiasis/*complications ; Young Adult ; }, abstract = {INTRODUCTION: Clinical researches have shown an increased bone disintegration and lower bone mass in patients with calcium urolithiasis.<br><br>GOAL: The goal of our research was to establish the incidence of osteoporosis in adult patients with calcium urolithiasis, on the basis of measuring mineral bone density, using DEXA method, with a special reflection on age subgroups.<br><br>MATERIAL AND METHODS: Clinical research was prospective and it was implemented at the University Clinical Center of Banja Luka, at the Clinic for Endocrinology, Diabetes and Metabolic Diseases and at the Urology Clinic. Material in this research consisted of patients divided in two groups, a working and a control group. One hundred and twenty (120) patients were included in both these groups, divided in three age subgroups: 20-40, 40-60 and over 60. The working group consisted of the patients with calcium urolithiasis and the control group consisted of patients without calcium urolithiasis. Establishing of mineral bone density at L2-L4 of lumbal spine vertebrae and hip was done for the patients in both these groups, using DEXA method.<br><br>RESULTS: Analysis of mineral bone density using DEXA method in patients in age groups of working and control groups, as well as in the total sample of working and control groups, have shown that the patients of the working group, over 60, had a decreased mineral bone density (30% of osteopenia and 15% osteoporosis) significantly more expressed when compared to the other two age groups (12.5% in the subgroup 20-40 and 17.5% in the subgroup 40-60), which presents a statistically significant difference (p<0.05). In the control group, when taking into account age groups, osteopenia and osteoporosis were marked in 37.5% and 2.5% in the group of patients over 60, whereas in the youngest population, 5% of osteopenia was found, which presents a statistically significant difference (p<0.05). When observing the total sample of working and control group, there was a statistically significant difference in the working and control group (p<0.01); incidence of osteoporosis in the working group amounted to 7.5% and in the control group it was 0.8%.<br><br>CONCLUSION: Urolithiasis and osteoporosis are two multifactorial diseases which are evidently reciprocal. This is why we suggest that educating the population about the risk factors for occurrence of these diseases as well as preventive measures that may contribute to their decrease should begin as early as possible.}, }
@article {pmid25530527, year = {2015}, author = {Iguchi, T and Nakatani, T}, title = {[Bone and Calcium Research Update 2015. Clinical update of urolithiasis--ESWL (extracorporeal shock wave lithotripsy)].}, journal = {Clinical calcium}, volume = {25}, number = {1}, pages = {97-104}, pmid = {25530527}, issn = {0917-5857}, mesh = {Animals ; Biomedical Research ; Bone and Bones/*metabolism ; Calcium/*metabolism ; Humans ; Kidney Calculi/diagnosis/*surgery ; *Lithotripsy/methods ; Treatment Outcome ; }, abstract = {ESWL (extracorporeal shock wave lithotripsy) is widely used for upper urinary stones and successfully treats most patients with uncomplicated kidney stones. ESWL is still of high strategic importance despite ureteroscopy and PNL occupy an essential place in the treatment of urinary stones by technologic advancements. However ESWL is just one of treatment tool and the best procedure should be selected for the patients. Moreover urolithiasis is one of lifestyle-related diseases and should be treated as systemic illness in the daily medical practice.}, }
@article {pmid25477375, year = {2015}, author = {Woods, SE and Leonard, MR and Hayden, JA and Brophy, MB and Bernert, KR and Lavoie, B and Muthupalani, S and Whary, MT and Mawe, GM and Nolan, EM and Carey, MC and Fox, JG}, title = {Impaired cholecystokinin-induced gallbladder emptying incriminated in spontaneous "black" pigment gallstone formation in germfree Swiss Webster mice.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {308}, number = {4}, pages = {G335-49}, pmid = {25477375}, issn = {1522-1547}, support = {P01 CA028842/CA/NCI NIH HHS/United States ; R01 DK062267/DK/NIDDK NIH HHS/United States ; P30 DK079338/DK/NIDDK NIH HHS/United States ; T32-OD10978-26/OD/NIH HHS/United States ; DK62267/DK/NIDDK NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; T32 OD010978/OD/NIH HHS/United States ; DK080480/DK/NIDDK NIH HHS/United States ; DK036588/DK/NIDDK NIH HHS/United States ; P30-ES002109/ES/NIEHS NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Bile Pigments/*metabolism ; Body Weight ; Calcium/metabolism ; Cholecystokinin/*metabolism ; Female ; Gallbladder/*metabolism/pathology/physiopathology ; Gallstones/*etiology/genetics/metabolism/pathology/physiopathology ; Genetic Predisposition to Disease ; Germ-Free Life ; Hydrogen-Ion Concentration ; Logistic Models ; Male ; Mice ; *Muscle Contraction ; Muscle, Smooth/*metabolism/pathology/physiopathology ; Risk Factors ; Sex Factors ; Species Specificity ; Time Factors ; }, abstract = {"Black" pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates ("hyperbilirubinbilia") from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice. GF SW mice were more likely to have gallstones than SPF SW mice, with 75% and 23% prevalence, respectively. In GF SW mice, gallstones were observed predominately in heavier, older females. Gallbladders of GF SW mice were markedly enlarged, contained sterile black gallstones composed of calcium bilirubinate and <1% cholesterol, and had low-grade inflammation, edema, and epithelial hyperplasia. Hemograms were normal, but serum cholesterol was elevated in GF compared with SPF SW mice, and serum glucose levels were positively related to increasing age. Aged GF and SPF SW mice had deficits in gallbladder smooth muscle activity. In response to cholecystokinin (CCK), gallbladders of fasted GF SW mice showed impaired emptying (females: 29%; males: 1% emptying), whereas SPF SW females and males emptied 89% and 53% of volume, respectively. Bilirubin secretion rates of GF SW mice were not greater than SPF SW mice, repudiating an induced EHC. Gallstones likely developed in GF SW mice because of gallbladder hypomotility, enabled by features of GF physiology, including decreased intestinal CCK concentration and delayed intestinal transit, as well as an apparent genetic predisposition of the SW stock. GF SW mice may provide a valuable model to study gallbladder stasis as a cause of black pigment gallstones.}, }
@article {pmid25446019, year = {2015}, author = {Figueres, ML and Linglart, A and Bienaime, F and Allain-Launay, E and Roussey-Kessler, G and Ryckewaert, A and Kottler, ML and Hourmant, M}, title = {Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {65}, number = {1}, pages = {122-126}, doi = {10.1053/j.ajkd.2014.06.037}, pmid = {25446019}, issn = {1523-6838}, mesh = {Bone Density Conservation Agents/pharmacology ; Calcium/metabolism ; Child ; Child, Preschool ; Diphosphonates/*pharmacology ; Female ; Fluid Therapy/*methods ; Humans ; *Hypercalcemia/genetics/physiopathology ; Hypercalciuria/genetics/physiopathology ; Infant ; Kidney Function Tests/methods ; Male ; Middle Aged ; Monitoring, Physiologic/methods ; Mutation ; *Nephrocalcinosis/etiology/metabolism/physiopathology ; *Nephrolithiasis/etiology/metabolism/physiopathology ; Parathyroid Hormone/blood ; Renal Insufficiency, Chronic/etiology/prevention &amp; control ; Seasons ; Sunlight/*adverse effects ; Treatment Outcome ; Vitamin D/*analogs &amp; derivatives/metabolism/pharmacology ; Vitamin D3 24-Hydroxylase/*genetics/metabolism ; }, abstract = {Loss-of-function mutations of CYP24A1, the enzyme that converts the major circulating and active forms of vitamin D to inactive metabolites, recently have been implicated in idiopathic infantile hypercalcemia. Patients with biallelic mutations in CYP24A1 present with severe hypercalcemia and nephrocalcinosis in infancy or hypercalciuria, kidney stones, and nephrocalcinosis in adulthood. We describe a cohort of 7 patients (2 adults, 5 children) presenting with severe hypercalcemia who had homozygous or compound heterozygous mutations in CYP24A1. Acute episodes of hypercalcemia in infancy were the first symptom in 6 of 7 patients; in all patients, symptoms included nephrocalcinosis, hypercalciuria, low parathyroid hormone (PTH) levels, and higher than expected 1,25-dihydroxyvitamin D levels. Longitudinal data suggested that in most patients, periods of increased sunlight exposure tended to correlate with decreases in PTH levels and increases in calcemia and calciuria. Follow-up of the 2 adult patients showed reduced glomerular filtration rate and extrarenal manifestations, including calcic corneal deposits and osteoporosis. Cases of severe PTH-independent hypercalcemia associated with hypercalciuria in infants should prompt genetic analysis of CYP24A1. These patients should be monitored carefully throughout life because they may be at increased risk for developing chronic kidney disease.}, }
@article {pmid25394514, year = {2015}, author = {He, D and Wang, S and Jia, Z and Cui, L and Lu, Y and Hu, H and Qin, B}, title = {Calcium ions promote primary renal epithelial cell differentiation into cells with bone-associated phenotypes via transforming growth factor-β1-induced epithelial-mesenchymal transition in idiopathic hypercalciuria patients.}, journal = {Molecular medicine reports}, volume = {11}, number = {3}, pages = {2199-2206}, doi = {10.3892/mmr.2014.2941}, pmid = {25394514}, issn = {1791-3004}, mesh = {Adult ; Bone Morphogenetic Protein 2/blood/genetics/metabolism ; Bone and Bones/metabolism ; Calcium/*metabolism ; Case-Control Studies ; Cell Line ; *Cell Transdifferentiation/drug effects ; Epithelial Cells/*metabolism ; *Epithelial-Mesenchymal Transition/drug effects ; Female ; Gene Expression ; Humans ; Hypercalciuria/genetics/*metabolism ; Kidney/cytology/*metabolism ; Male ; Middle Aged ; Nephrolithiasis/genetics/metabolism ; Osteopontin/blood/metabolism ; Phenotype ; Transforming Growth Factor beta1/blood/*metabolism/pharmacology ; Young Adult ; }, abstract = {The present study aimed to identify the characteristics and cross‑talk between transforming growth factor β1 (TGF‑β1) and calcium ions in nephrolithiasis patients with idiopathic hypercalciuria (IH) in order to elucidate the potential mechanisms underlying changes in cell phenotype induced by bone‑associated factors and their influence on renal nephrolithiasis formation. Blood samples from a total of 29 nephrolithiasis patients with IH, 29 renal stone patients without IH and 29 healthy age‑matched normal controls were subjected to quantification of peripheral serum TGF‑β1, osteopontin (OPN) and bone morphogenetic protein 2 (BMP2) using ELISA. This was followed by detection of BMP2, OPN and 1,25‑dihydroxyvitamin D3 receptor (VDR) mRNA and protein levels in primary renal epithelial cells (PRECs) of IH and HK‑2 human proximal tubular cell lines (control) using reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses. The mRNA expression levels of BMP2, OPN and VDR in PRECs and HK‑2 were evaluated following stimulation with various concentrations of TGF‑β1 (0.5, 2.0 and 5.0 ng/ml), Ca2+ (0.5, 1.5 and 2.5 mM) or TGF‑β1 and Ca2+ combined using RT‑qPCR, respectively. TGF‑β1, BMP2 and OPN expression levels in patients with IH were all significantly higher than those in the control group. The mRNA and protein expression levels of BMP2 and VDR were significantly higher in PRECs than those in HK‑2 cells. Following incubation with TGF‑β1 and/or Ca2+, the mRNA expression levels of BMP2, OPN and VDR in PRECs increased in a dose‑dependent manner; however, no significant differences were observed in HK‑2 cells with increasing TGF‑β1 dosage. Co‑incubation with TGF‑β1 and Ca2+ in PRECs and HK‑2 cell lines resulted in similar effects and the expression of BMP2, OPN and VDR mRNA increased in a time‑dependent manner. In conclusion, the results of the present study demonstrated that TGF‑β1 regulated the expression of BMP2, OPN and VDR in PRECs, but not in HK‑2 cells. Co‑incubation with TGF‑β1 and Ca2+ significantly increased the expression levels of bone‑associated factors in PRECs and HK‑2 cells, which suggested that this process may be partially responsible for the pathogenesis of calcium stone development, and also associated with bone formation and the TGF‑β1‑induced epithelial to mesenchymal transition.}, }
@article {pmid25310585, year = {2014}, author = {Zhang, H and Li, N and Li, K and Li, P}, title = {Protective effect of Urtica dioica methanol extract against experimentally induced urinary calculi in rats.}, journal = {Molecular medicine reports}, volume = {10}, number = {6}, pages = {3157-3162}, doi = {10.3892/mmr.2014.2610}, pmid = {25310585}, issn = {1791-3004}, mesh = {Ammonium Chloride/pharmacology ; Animals ; Calcium/metabolism ; Calcium Oxalate/metabolism ; Chlorogenic Acid/chemistry/pharmacology ; Creatinine/metabolism ; Ethylene Glycol/pharmacology ; Flavonoids/chemistry/pharmacology ; Hydroxybenzoates/chemistry/pharmacology ; Kaempferols/chemistry/pharmacology ; Kidney/drug effects/metabolism ; Luteolin/chemistry/pharmacology ; Male ; Methanol/*chemistry ; Monosaccharides/chemistry/pharmacology ; Oxalates/metabolism ; Plant Extracts/*chemistry/*pharmacology ; Protective Agents/*chemistry/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Rutin/chemistry/pharmacology ; Salicylic Acid/chemistry/pharmacology ; Urinary Calculi/*drug therapy ; Urtica dioica/*chemistry ; }, abstract = {Renal calculi formation is one of the most common urological disorders. Urinary stone disease is a common disease, which affects 10‑12% of the population in industrialized countries. In males, the highest prevalence of the disease occurs between the age of 20 and 40 years, while in females, the highest incidence of the disease occurs later. Previous studies have shown that long‑term exposure to oxalate is toxic to renal epithelial cells and results in oxidative stress. In the present study, a methanolic extract of aerial parts of Urtica dioica was screened for antiurolithiatic activity against ethylene glycol and ammonium chloride‑induced calcium oxalate renal stones in male rats. In the control rats, ethylene glycol and ammonium chloride administration was observed to cause an increase in urinary calcium, oxalate and creatinine levels, as well as an increase in renal calcium and oxalate deposition. Histopathological observations revealed calcium oxalate microcrystal deposits in the kidney sections of the rats treated with ethylene glycol and ammonium chloride, indicating the induction of lithiasis. In the test rats, treatment with the methanolic extract of Urtica dioica was found to decrease the elevated levels of urinary calcium, oxalate and creatinine, and significantly decrease the renal deposition of calcium and oxalate. Furthermore, renal histological observations revealed a significant reduction in calcium oxalate crystal deposition in the test rats. Phytochemical analysis of the Urtica dioica extract was also performed using liquid chromatography‑electrospray ionization tandem mass spectrometry and high-performance liquid chromatography with photodiode array detection, to determine the chemical composition of the extract. The eight chemical constituents identified in the extract were protocatechuic acid, salicylic acid, luteolin, gossypetin, rutin, kaempferol‑3‑O‑rutinoside, kaempferol‑3‑O‑glucoside and chlorogenic acid. In conclusion, the results of the present study suggest that Urtica dioica has strong antiurolithiatic activity and may have potential as a natural therapeutic agent for various urological disorders.}, }
@article {pmid25266216, year = {2015}, author = {Fabris, A and Ferraro, PM and Comellato, G and Caletti, C and Fantin, F and Zaza, G and Zamboni, M and Lupo, A and Gambaro, G}, title = {The relationship between calcium kidney stones, arterial stiffness and bone density: unraveling the stone-bone-vessel liaison.}, journal = {Journal of nephrology}, volume = {28}, number = {5}, pages = {549-555}, pmid = {25266216}, issn = {1724-6059}, mesh = {Absorptiometry, Photon ; Blood Flow Velocity/*physiology ; Blood Vessels/*physiopathology ; Bone Density/*physiology ; Calcium/*metabolism ; Cardiovascular Diseases/epidemiology/*etiology/physiopathology ; Follow-Up Studies ; Humans ; Italy/epidemiology ; Kidney Calculi/complications/*metabolism/physiopathology ; Prevalence ; Prospective Studies ; Pulse Wave Analysis/methods ; Vascular Stiffness/*physiology ; }, abstract = {BACKGROUND AND OBJECTIVES: Kidney stone disease is associated with a higher incidence of cardio-vascular (CV) events for still unclear reasons. Reduced bone density is also a frequent finding in calcium kidney stones. The association of reduced bone density with increased vascular stiffness and calcification has been discovered in a number of conditions. We investigated the hypothesis that patients with calcium kidney stones have increased arterial stiffness, which would be associated with reduced bone density and higher CV risk.<br><br>We compared measures of arterial stiffness [carotid-radial pulse-wave velocity (CR-PWV), carotid-femoral pulse-wave velocity (CF-PWV) and augmentation index (AI)] and of bone density (T-scores determined at lumbar spine, neck and hip) among 42 idiopathic calcium stone formers compared with 42 age- and sex-matched healthy volunteers.<br><br>RESULTS: Stone formers had higher values of CR-PWV, CF-PWV and AI, and lower values of all T-scores. Furthermore, the prevalence of abnormal arterial stiffness and reduced bone density was significantly higher among stone formers. Statistical adjustment for age, sex, body mass index and other covariates did not change the results.<br><br>CONCLUSIONS: Our study confirms that stone formers have increased arterial stiffness and reduced bone density. Abnormal arterial stiffness appears to be independent of reduced bone density and may explain the higher CV risk observed in stone formers.}, }
@article {pmid25216416, year = {2014}, author = {Dorairajan, N and Pradeep, PV}, title = {Vignette hyperparathyroidism: glimpse into its history.}, journal = {International surgery}, volume = {99}, number = {5}, pages = {528-533}, pmid = {25216416}, issn = {2520-2456}, mesh = {History, 19th Century ; History, 20th Century ; Humans ; Hyperparathyroidism/*history ; Hyperparathyroidism, Primary/history ; Parathyroidectomy/history ; }, abstract = {The parathyroid gland was first described by Sir Richard Owen. Ivor Sandstrom coined the term glandulae parathyroidiae. Vassale and Generali Francesco observed that tetany occurs following parathyroidectomy. Harald Salvesen firmly established the relationship of the parathyroid gland to calcium metabolism. A patient with skeletal disease and a tumor near the parathyroid gland was described by Max Askanazy in 1904. Schlagenhaufer suggested in 1915 that in an attempt to cure bone disease, solitary parathyroid enlargement, if present, should be excised. The term hyperparathyroidism (HPT) was coined by Henry Dixon and colleagues. The parathyroid surgeries on Albert J. and Charles Martell were the first experience with successful parathyroidectomy. From a grossly symptomatic disease of bones, stones, abdominal groans, and psychic moans, HPT has evolved into asymptomatic HPT. Improvements in knowledge about the pathology of parathyroid diseases, including the genetic basis of HPT, and advances in the surgical techniques have brought about changes in the management of HPT over the decades.}, }
@article {pmid25192523, year = {2014}, author = {Balestracci, A and Meni Battaglia, L and Toledo, I and Martin, SM and Wainsztein, RE}, title = {Idiopathic hypercalciuria in children with urinary tract infection.}, journal = {Archivos argentinos de pediatria}, volume = {112}, number = {5}, pages = {428-433}, doi = {10.5546/aap.2014.eng.428}, pmid = {25192523}, issn = {1668-3501}, mesh = {Adolescent ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Hypercalciuria/*complications/*epidemiology ; Infant ; Male ; Prevalence ; Sodium Chloride, Dietary/administration &amp; dosage ; Urinary Tract Infections/*complications ; Vesico-Ureteral Reflux/complications ; }, abstract = {INTRODUCTION: Idiopathic hypercalciuria (IH) predisposes to urinary tract infections (UTIs); however, there is scarce local information regarding such association. Our objectives were to estimate IH prevalence in children with UTI and to assess whether there were differences in relation to the presence or absence of vesicoureteral reflux (VUR). Additionally, the association between IH and salt intake was studied.<br><br>POPULATION AND METHODS: Calciuria was determined in patients younger than 18 years old on whom UTI had been studied (ultrasound and voiding cystourethrogram), and who had no secondary causes of hypercalciuria. IH was defined as a calcium to creatinine ratio of >0.8, 0.6, 0.5 and 0.2 in children aged 0 to 6 months old, 7 to12 months old, 12 to 24 months old and older than 2 years old, respectively; and a high sodium intake with a urinary sodium to potassium ratio of >2.5.<br><br>RESULTS: IH prevalence among 136 patients (87 girls, median age: 3 years old) was 20%. Patients with VUR (n= 54) and without VUR (n= 82) had similar characteristics in terms of sex, weight, height, age at diagnosis and age at the time of the study, and clinical features (hematuria, nephrolithiasis, colicky pain, and recurrent UTI), family history of kidney stone formation, and IH prevalence (26% versus 16%, p= 0.24). A high sodium intake was more frequently observed in children with hypercalciuria than in those with normal urine calcium levels (76% versus 46%, p= 0.007).<br><br>CONCLUSIONS: IH prevalence in children with UTI was high (20%), with no differences observed between patients with and without VUR. As a recommendation, the presence of IH should be detected in children with UTI, regardless of VUR presence or absence.}, }
@article {pmid25188231, year = {2014}, author = {Arrabal-Polo, MA and Cano-García, Mdel C and Canales, BK and Arrabal-Martín, M}, title = {Calcium nephrolithiasis and bone demineralization: pathophysiology, diagnosis, and medical management.}, journal = {Current opinion in urology}, volume = {24}, number = {6}, pages = {633-638}, doi = {10.1097/MOU.0000000000000111}, pmid = {25188231}, issn = {1473-6586}, mesh = {Bone Demineralization, Pathologic/diagnosis/drug therapy/*metabolism ; Calcium/*metabolism ; Humans ; Hypercalciuria/diagnosis/drug therapy/*metabolism ; Nephrolithiasis/diagnosis/drug therapy/*metabolism ; Osteoporosis/diagnosis/drug therapy/*metabolism ; }, abstract = {PURPOSE OF REVIEW: To establish the relationship between calcium nephrolithiasis, bone densitometry scoring, and bone mineral density (BMD) loss according to bone turnover markers (BTMs) and urinary metabolites.<br><br>RECENT FINDINGS: Patients with recurrent calcium nephrolithiasis and idiopathic fasting hypercalciuria (urinary calcium/creatinine ratio >0.11) are more likely to have BMD loss that may lead to osteopenia or osteoporosis. In these patients, BTMs may be used as a surrogate for both bone health and stone recurrence. Suspect higher lithogenic states when calcium stone formers have serum beta-crosslaps (resorptive marker) greater than 0.311&#x200a;ng/ml, serum osteocalcin (formative marker) greater than 13.2&#x200a;ng/ml, and beta-crosslaps/osteocalcin ratio greater than 0.024.<br><br>SUMMARY: Patients with recurrent calcium nephrolithiasis and fasting hypercalciuria have a higher incidence of osteopenia and osteoporosis, measured by the dual-energy X-ray absorptiometry. These patients present not only with hypercalciuria and increased BTMs (mainly resorptive), but also up to 30% have hypocitraturia and increased urinary calcium/citrate ratio (>0.25). On the basis of these results, a diagnostic algorithm was created, classifying hypercalciurics according to their fasting calcium/creatinine and calcium/citrate ratio. Medical therapy for these patients is aimed at improving the dietary habits (normocalcemic, low salt, low animal protein diet), prescribing combinations of potassium citrate, thiazides, and bisphosphonates, and correcting bone and urinary abnormalities that may lower future skeletal and kidney stone risk.}, }
@article {pmid26816783, year = {2014}, author = {Nouvenne, A and Ticinesi, A and Morelli, I and Guida, L and Borghi, L and Meschi, T}, title = {Fad diets and their effect on urinary stone formation.}, journal = {Translational andrology and urology}, volume = {3}, number = {3}, pages = {303-312}, pmid = {26816783}, issn = {2223-4691}, abstract = {The influence of unhealthy dietary habits on urinary stone formation has been widely recognized in literature. Dietary advice is indeed the cornerstone prescription for prevention of nephrolithiasis as well. However, only a small amount of medical literature has addressed the influence of popular or fad diets, often self-prescribed for the management of obesity and overweight or for cultural beliefs, on the risk of kidney stones. Thereby in this paper we analyze the current knowledge on the effects of some popular diets on overall lithogenic risk. High-protein diets, like Dukan diet, raise some concerns, since animal proteins are able to increase urinary calcium and to decrease urinary citrate excretion, thus leading to a high overall lithogenic risk. Low-carbohydrate diets, like Atkins diet or zone diet, may have a protective role against kidney stone formation, but there are also evidences stating that this dietary approach may rise calciuria and decrease citraturia, since it is generally associated to a relatively high intake of animal proteins. Vegan diet can be harmful for urinary stone disease, especially for the risk of hyperuricemia and micronutrient deficiencies, even if only few studies have addressed this specific matter. On the other side, the benefits of a lacto-ovo-vegetarian diet on kidney stone prevention have been largely emphasized, provided that the intake of calcium and oxalate is balanced. Traditional Mediterranean diet should exert a protective effect on nephrolithiasis as well, even if specific studies have not been carried out yet. High phytate and antioxidant content of this diet have however demonstrated to be beneficial in preventing the formation of new or recurrent calculi. Anyway, at the current state of knowledge, the most effective dietary approach to prevent kidney stone disease is a mild animal protein restriction, a balanced intake of carbohydrates and fats and a high intake of fruit and vegetables. Other fundamental aspects, which are often neglected in fad diets, are a normal intake of milk and dairy products and salt restriction. All these nutritional aspects should be greatly taken into account when patients who are willing to undergo fad or commercial diets ask for dietary advice.}, }
@article {pmid25080794, year = {2014}, author = {Razmakhnin, EV and Khyshiktuev, BS and Kichigina, VA and Namdakov, BB}, title = {[The atomic emission analysis under examination of composition of gallstones].}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {}, number = {4}, pages = {11-13}, pmid = {25080794}, issn = {0869-2084}, mesh = {Calcium/*metabolism ; Caprylates/*metabolism ; Female ; Gallstones/diagnosis/*metabolism/surgery ; Humans ; Male ; Prognosis ; *Spectrophotometry, Atomic ; }, abstract = {The high morbidity of cholelithiasis and considerable percentage of complications dictates necessity to search new little invasive modes of treatment. In this, one of the perspective directions is the application of dissolution of concrements using contact litholysis. The solubility of concrements directly depends on their composition. The detailed knowledge of composition of gallstones subjected to dissolution is needed for prognosis of solubility of concrements and experimental findings of new solvents. The mode of atomic emission analysis was applied to study mineral composition of 105 gallstones extracted from gallbladders of patients with cholelithiasis operated using laparoscopy. The experimental studies were implemented in vitro on dissolution of concrements depending on their composition and using octane acid. It is established that solubility of gallstones depends on content of calcium and ash composition of concrements. In consideration of relative simplicity of application, absence of complicated preparation of tests for analysis, distinct dependence of solubility of concrements on content of calcium and ash content of gallstones the atomic emission analysis can be recommended for examination of composition of gall concrements in case of search and development of new modes of litholysis. This mode of analysis can be also applied for prognosis of dissolution of concrements under application of contact litholysis.}, }
@article {pmid25071082, year = {2015}, author = {Gong, Y and Himmerkus, N and Plain, A and Bleich, M and Hou, J}, title = {Epigenetic regulation of microRNAs controlling CLDN14 expression as a mechanism for renal calcium handling.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {26}, number = {3}, pages = {663-676}, pmid = {25071082}, issn = {1533-3450}, support = {P30 DK079333/DK/NIDDK NIH HHS/United States ; R01 DK084059/DK/NIDDK NIH HHS/United States ; P30-DK079333/DK/NIDDK NIH HHS/United States ; R01-DK084059/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism ; Cinacalcet ; Claudins/*metabolism ; Epigenesis, Genetic ; Gene Expression Regulation ; Histone Deacetylase Inhibitors ; Hypercalciuria/genetics ; Hypocalcemia/genetics ; Hypoparathyroidism/congenital/genetics ; Kidney/*metabolism ; Magnesium/urine ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; MicroRNAs/*metabolism ; Naphthalenes ; Receptors, Calcium-Sensing/genetics/*metabolism ; }, abstract = {The kidney has a major role in extracellular calcium homeostasis. Multiple genetic linkage and association studies identified three tight junction genes from the kidney--claudin-14, -16, and -19--as critical for calcium imbalance diseases. Despite the compelling biologic evidence that the claudin-14/16/19 proteins form a regulated paracellular pathway for calcium reabsorption, approaches to regulate this transport pathway are largely unavailable, hindering the development of therapies to correct calcium transport abnormalities. Here, we report that treatment with histone deacetylase (HDAC) inhibitors downregulates renal CLDN14 mRNA and dramatically reduces urinary calcium excretion in mice. Furthermore, treatment of mice with HDAC inhibitors stimulated the transcription of renal microRNA-9 (miR-9) and miR-374 genes, which have been shown to repress the expression of claudin-14, the negative regulator of the paracellular pathway. With renal clearance and tubule perfusion techniques, we showed that HDAC inhibitors transiently increase the paracellular cation conductance in the thick ascending limb. Genetic ablation of claudin-14 or the use of a loop diuretic in mice abrogated HDAC inhibitor-induced hypocalciuria. The genetic mutations in the calcium-sensing receptor from patients with autosomal dominant hypocalcemia (ADH) repressed the transcription of miR-9 and miR-374 genes, and treatment with an HDAC inhibitor rescued the phenotypes of cell and animal models of ADH. Furthermore, systemic treatment of mice with antagomiRs against these miRs relieved claudin-14 gene silencing and caused an ADH-like phenotype. Together, our findings provide proof of concept for a novel therapeutic principle on the basis of epigenetic regulation of renal miRs to treat hypercalciuric diseases.}, }
@article {pmid25069966, year = {2014}, author = {Xie, R and Tang, B and Yong, X and Luo, G and Yang, SM}, title = {Roles of the calcium sensing receptor in digestive physiology and pathophysiology (review).}, journal = {International journal of oncology}, volume = {45}, number = {4}, pages = {1355-1362}, doi = {10.3892/ijo.2014.2560}, pmid = {25069966}, issn = {1791-2423}, mesh = {Animals ; Calcium/*metabolism ; Calcium Metabolism Disorders/metabolism/pathology ; Digestive System Physiological Phenomena ; Gastrointestinal Diseases/drug therapy/genetics/metabolism/*pathology ; Humans ; Molecular Targeted Therapy ; Receptors, Calcium-Sensing/agonists/*genetics/*metabolism ; }, abstract = {Calcium participates in most of the biological processes in the human body. The calcium sensing receptor (CaSR), as an important regulator of calcium homeostasis, is expressed in all of the organs of the digestive system. CaSR plays a key role in gastrointestinal physiological function and in the occurrence of digestive disease. For example, the inactivation or mutation of the CaSR gene usually leads to one of several disorders of calcium metabolism. High dietary Ca2+ may stimulate CaSR activation and could both inhibit tumor development and increase the chemotherapeutic sensitivity of cancer cells in colon cancer tissues. Further, CaSR has also been reported to have a potential role in the treatment for diarrheal diseases and the form of pancreatitis that is associated with carbonate stones. Therefore, CaSR is an important target for treating digestive diseases, and the calcimimetics (CaSR agonist) have been confirmed as practical, feasible and effective clinical therapies for hyperparathyroidism. This review intends to explore the role of CaSR in digestive physiology and pathophysiology as well as current treatments utilizing CaSR‑based therapeutics.}, }
@article {pmid25055352, year = {2014}, author = {Ramos, MF and de Santana, LG and Rasvickas, CV and Teixeira, Vde P and Schor, N}, title = {Effect of vitamin D3 overdose and calcium supplementation in experimental nephrolithiasis model.}, journal = {Jornal brasileiro de nefrologia : 'orgao oficial de Sociedades Brasileira e Latino-Americana de Nefrologia}, volume = {36}, number = {2}, pages = {132-138}, doi = {10.5935/0101-2800.20140022}, pmid = {25055352}, issn = {2175-8239}, mesh = {Animals ; Calcium/*administration &amp; dosage ; Cholecalciferol/administration &amp; dosage/*adverse effects ; Dietary Supplements ; Disease Models, Animal ; Drug Overdose ; Nephrolithiasis/*chemically induced ; Rats ; Rats, Wistar ; Vitamins/administration &amp; dosage/*adverse effects ; }, abstract = {INTRODUCTION: There is little information in the literature relating supplementary oral usage of vitamin D and calcium to the development of kidney stones.<br><br>OBJECTIVE: To evaluate the effect of high dose, 200 IU of vitamin D3 (V) with calcium supplementation (Ca).<br><br>METHODS: Experimental model consists of insertion of pellets into the bladder of rats. V was administered for 30 days with or without Ca. The rats were divided in 6 groups: 1. Sham, 2. Pellets control; 3. V control; 4. Pellets + V; 5. Pellets + Ca and 6. Pellets + Ca + V.<br><br>RESULTS: 50% and 17% decreases bladder stones formation in groups 5 and 6, p < 0.005 comparing with the group 2 were observed. There was no hypercalcemia or hypercalciuria in all groups. We observed a significant decrease in calciuria in group 6 (p = 0.03).<br><br>CONCLUSION: The administration of the V associated with Ca significantly decreased the formation of stones and caused a significant reduction in urinary calcium, suggesting a protection in the lithogenic pathophysiology.}, }
@article {pmid25048492, year = {2014}, author = {Kim, WT and Kim, YJ and Yun, SJ and Shin, KS and Choi, YD and Lee, SC and Kim, WJ}, title = {Role of 1,25-dihydroxy vitamin D3 and parathyroid hormone in urinary calcium excretion in calcium stone formers.}, journal = {Yonsei medical journal}, volume = {55}, number = {5}, pages = {1326-1332}, pmid = {25048492}, issn = {1976-2437}, mesh = {Adult ; Calcium/metabolism/*urine ; Female ; Humans ; Kidney Calculi ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Parathyroid Hormone/blood/*physiology/urine ; Vitamin D/*analogs &amp; derivatives/blood/physiology/urine ; }, abstract = {PURPOSE: To find out the possible role of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] and parathyroid hormone (PTH) as intrinsic factors in urinary calcium stone formers (SFs), we investigated their relationship with serum and urinary biochemical parameters.<br><br>MATERIALS AND METHODS: A total of 326 calcium SFs (male: 204, female: 122) were enrolled and underwent outpatient metabolic evaluations including 1,25(OH)&#x2082;D&#x2083; and PTH as well as serum and 24-hour urinary biochemical parameters. As control, 163 age- and sex-matched (2:1) individuals (non-SFs) who have never urinary stone episode were included.<br><br>RESULTS: 1,25(OH)&#x2082;D&#x2083; level was positively correlated with urinary calcium excretion (r=0.347, p<0.001). The hypercalciuric group and recurrent SFs had higher serum 1,25(OH)&#x2082;D&#x2083; levels than the normocalciuric group (p<0.001) and first SFs (p=0.050). In the adjusted multiple linear regression analysis, serum 1,25(OH)&#x2082;D&#x2083; level (&#x3b2;=0.259, p<0.001) and serum PTH level (&#x3b2;=-0.160, p<0.001) were significantly correlated with urinary calcium excretion. The patients in highest tertile of 1,25(OH)&#x2082;D&#x2083; had a more than 3.1 fold risk of hypercalciuria than those in the lowest tertile (odds ratio=3.14, 95% confidence interval: 1.431-6.888, p=0.004). No correlation was observed between PTH and 1,25(OH)&#x2082;D&#x2083; (R=0.005, p=0.929) in calcium SFs, while a negative correlation was found in controls (R=-0.269, p=0.001).<br><br>CONCLUSION: 1,25(OH)&#x2082;D&#x2083; was closely correlated with urinary calcium excretion, and high 1,25(OH)&#x2082;D&#x2083; levels were detected in the hypercalciuric group and in recurrent SFs. However, 1,25(OH)&#x2082;D&#x2083; was not correlated with PTH in calcium SFs. These findings suggest that 1,25(OH)&#x2082;D&#x2083; might be important intrinsic factor for altered calcium regulation in SFs.}, }
@article {pmid24992569, year = {2014}, author = {Toka, HR and Pollak, MR}, title = {The role of the calcium-sensing receptor in disorders of abnormal calcium handling and cardiovascular disease.}, journal = {Current opinion in nephrology and hypertension}, volume = {23}, number = {5}, pages = {494-501}, doi = {10.1097/MNH.0000000000000042}, pmid = {24992569}, issn = {1473-6543}, mesh = {Animals ; Bone Remodeling ; Calcium/*metabolism ; Calcium Signaling ; Cardiovascular Diseases/genetics/*metabolism/physiopathology ; Genetic Predisposition to Disease ; Homeostasis ; Humans ; Hypercalcemia/genetics/metabolism/physiopathology ; Hypercalciuria/genetics/metabolism/physiopathology ; Kidney Calculi/genetics/metabolism/physiopathology ; Mutation ; Phenotype ; Receptors, Calcium-Sensing/genetics/*metabolism ; Vascular Calcification/genetics/metabolism/physiopathology ; }, abstract = {PURPOSE OF REVIEW: The calcium-sensing receptor (CaSR) has a central role in parathyroid gland function. Genetic alterations in CaSR are well known to cause inherited forms of abnormal calcium homeostasis. This review focuses on studies investigating the role of CaSR in common disorders of abnormal calcium handling and in cardiovascular calcification.<br><br>RECENT FINDINGS: Genetic population studies tested the association of common allelic CASR variants with serum and urine calcium levels, kidney stone disease, primary hyperparathyroidism and bone mineral density. The results of these association studies suggested either minor or no effects of CASR variants in these phenotypes. Decreased expression of CaSR was associated with the etiology of cardiovascular calcification in individuals with advanced chronic kidney disease.<br><br>SUMMARY: Ionized calcium plays a central role in the physiology of many organ systems and disease states, but the roles of CaSR other than as illustrated by Mendelian forms of CaSR dysfunction remain unclear. The contributions of CaSR to bone mineral homeostasis, vascular calcification and other forms of cardiovascular disease need further investigation.}, }
@article {pmid24832105, year = {2014}, author = {Gerasimenko, J and Peng, S and Gerasimenko, O}, title = {Role of acidic stores in secretory epithelia.}, journal = {Cell calcium}, volume = {55}, number = {6}, pages = {346-354}, doi = {10.1016/j.ceca.2014.04.002}, pmid = {24832105}, issn = {1532-1991}, mesh = {Acinar Cells/cytology/*metabolism ; Animals ; Calcium/metabolism ; Calcium Signaling ; Calmodulin/metabolism ; Endoplasmic Reticulum/metabolism ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Pancreas, Exocrine/cytology ; Vacuolar Proton-Translocating ATPases/metabolism ; }, abstract = {There is growing evidence that intracellular calcium plays a primary role in the pathophysiology of the pancreas in addition to its crucial importance in major physiological functions. Pancreatic acinar cells have a remarkably large amount of Ca(2+) stored in both the endoplasmic reticulum (ER) and the acidic stores. The vast majority of the classical ER Ca(2+) store is located in the basal part of the acinar cells with extensions protruding into the apical area, however, the acidic stores are exclusively located in the secretory granular area of the cells. Both types of Ca(2+) store respond to all three intracellular Ca(2+) messengers - inositol trisphosphate (InsP3), cyclic-ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). The two stores interact with each other via calcium-induced calcium release; however, they can be separated using pharmacological tools. The ER relies on sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) that can be blocked by the specific inhibitor thapsigargin. The acidic store requires a low pH that can be modified by blocking vacuolar H(+)-ATPase. The acidic store is particularly important for pathological processes in the pancreas. Acute pancreatitis is initiated as a result of calcium overload in the apical pole, which leads to trypsinogen activation; two major causes are gall bladder stones and excessive alcohol consumption. Excessive Ca(2+) release from the acidic stores plays a major role in both scenarios; however NAADP-induced calcium release from acidic stores is particularly important for bile-induced pancreatitis. Cell-permeable calmodulin (CaM) activators such as CALP3 boost the natural protective effect of CaM by inhibiting excessive calcium release from the internal stores through inositol trisphosphate (InsP3R) and ryanodine receptors (RyR). Alternatively calcium overload can be dramatically reduced by inhibiting Ca(2+)-release-activated Ca(2+) (CRAC) currents that are required to reload the internal stores and therefore provide effective protection against the major triggers of acute pancreatitis.}, }
@article {pmid24756712, year = {2014}, author = {Na, T and Peng, JB}, title = {TRPV5: a Ca(2+) channel for the fine-tuning of Ca(2+) reabsorption.}, journal = {Handbook of experimental pharmacology}, volume = {222}, number = {}, pages = {321-357}, doi = {10.1007/978-3-642-54215-2_13}, pmid = {24756712}, issn = {0171-2004}, support = {R01DK072154/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Black People/genetics ; Calcium/*metabolism ; Calcium Channels/chemistry/deficiency/genetics/*metabolism ; *Calcium Signaling ; Genetic Predisposition to Disease ; Humans ; Mice ; Mice, Knockout ; Phenotype ; Polymorphism, Single Nucleotide ; Protein Conformation ; Structure-Activity Relationship ; TRPV Cation Channels/chemistry/deficiency/genetics/*metabolism ; }, abstract = {TRPV5 is one of the two channels in the TRPV family that exhibit high selectivity to Ca(2+) ions. TRPV5 mediates Ca(2+) influx into cells as the first step to transport Ca(2+) across epithelia. The specialized distribution in the distal tubule of the kidney positions TRPV5 as a key player in Ca(2+) reabsorption. The responsiveness in expression and/or activity of TRPV5 to hormones such as 1,25-dihydroxyvitamin D3, parathyroid hormone, estrogen, and testosterone makes TRPV5 suitable for its role in the fine-tuning of Ca(2+) reabsorption. This role is further optimized by the modulation of TRPV5 trafficking and activity via its binding partners; co-expressed proteins; tubular factors such as calbindin-D28k, calmodulin, klotho, uromodulin, and plasmin; extracellular and intracellular factors such as proton, Mg(2+), Ca(2+), and phosphatidylinositol-4,5-bisphosphate; and fluid flow. These regulations allow TRPV5 to adjust its overall activity in response to the body's demand for Ca(2+) and to prevent kidney stone formation. A point mutation in mouse Trpv5 gene leads to hypercalciuria similar to Trpv5 knockout mice, suggesting a possible role of TRPV5 in hypercalciuric disorders in humans. In addition, the single nucleotide polymorphisms in Trpv5 gene prevalently present in African descents may contribute to the efficient renal Ca(2+) reabsorption among African descendants. TRPV5 represents a potential therapeutic target for disorders with altered Ca(2+) homeostasis.}, }
@article {pmid24652587, year = {2014}, author = {Hering-Smith, KS and Mao, W and Schiro, FR and Coleman-Barnett, J and Pajor, AM and Hamm, LL}, title = {Localization of the calcium-regulated citrate transport process in proximal tubule cells.}, journal = {Urolithiasis}, volume = {42}, number = {3}, pages = {209-219}, pmid = {24652587}, issn = {2194-7236}, support = {R01 DK054952/DK/NIDDK NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; NIH DK54952/DK/NIDDK NIH HHS/United States ; P20 RR017659/RR/NCRR NIH HHS/United States ; P20RR017659/RR/NCRR NIH HHS/United States ; P30 GM103337/GM/NIGMS NIH HHS/United States ; R01 DK095879/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biological Transport/drug effects/physiology ; Calcium/*metabolism ; Cell Line ; Cell Polarity/drug effects/physiology ; Citrates/*metabolism ; Dicarboxylic Acid Transporters/genetics/*metabolism ; Kidney Cortex/cytology/metabolism ; Kidney Tubules, Proximal/cytology/*metabolism ; Nephrolithiasis/*metabolism/pathology ; Opossums ; Organic Anion Transporters, Sodium-Dependent/genetics/*metabolism ; RNA, Messenger/metabolism ; Rats ; Succinates/pharmacology ; Succinic Acid/metabolism ; Symporters/genetics/*metabolism ; }, abstract = {Urinary citrate is an important inhibitor of calcium-stone formation. Most of the citrate reabsorption in the proximal tubule is thought to occur via a dicarboxylate transporter NaDC1 located in the apical membrane. OK cells, an established opossum kidney proximal tubule cell line, transport citrate but the characteristics change with extracellular calcium such that low calcium solutions stimulate total citrate transport as well as increase the apparent affinity for transport. The present studies address several fundamental properties of this novel process: the polarity of the transport process, the location of the calcium-sensitivity and whether NaDC1 is present in OK cells. OK cells grown on permeable supports exhibited apical >basolateral citrate transport. Apical transport of both citrate and succinate was sensitive to extracellular calcium whereas basolateral transport was not. Apical calcium, rather than basolateral, was the predominant determinant of changes in transport. Also 2,3-dimethylsuccinate, previously identified as an inhibitor of basolateral dicarboxylate transport, inhibited apical citrate uptake. Although the calcium-sensitive transport process in OK cells is functionally not typical NaDC1, NaDC1 is present in OK cells by Western blot and PCR. By immunolocalization studies, NaDC1 was predominantly located in discrete apical membrane or subapical areas. However, by biotinylation, apical NaDC1 decreases in the apical membrane with lowering calcium. In sum, OK cells express a calcium-sensitive/regulated dicarboxylate process at the apical membrane which responds to variations in apical calcium. Despite the functional differences of this process compared to NaDC1, NaDC1 is present in these cells, but predominantly in subapical vesicles.}, }
@article {pmid24649757, year = {2013}, author = {Dzerganov, NK and Egshatian, LV and Mokrysheva, NG and Peretokina, EV}, title = {[Clinical and laboratory parameters in patients with urolithiasis in the presence and absence of primary hyperparathyroidism].}, journal = {Urologiia (Moscow, Russia : 1999)}, volume = {}, number = {6}, pages = {14-18}, pmid = {24649757}, issn = {1728-2985}, mesh = {Adult ; Aged ; Aged, 80 and over ; Calcium/blood/urine ; Chlorides/blood/urine ; Female ; Humans ; Hyperparathyroidism/*blood/complications/diagnosis/*urine ; Lipoproteins, HDL/blood/urine ; Magnesium/blood/urine ; Male ; Middle Aged ; Parathyroid Hormone/blood/urine ; Phosphorus/blood/urine ; Triglycerides/blood/urine ; Urolithiasis/*blood/complications/diagnosis/*urine ; }, abstract = {The clinical and laboratory findings in 78 patients with various forms of urolithiasis depending on the presence of primary hyperparathyroidism (PHPT) were analyzed. PHPT was diagnosed in 17 patients. Group "without PHPT" and group "with PHPT" differed significantly in terms of parathyroid hormone (PTH) level, serum calcium, phosphorus, chloride, alkaline phosphatase, calciuria and kaliuria. In patients with staghorn calculi, PHPT was diagnosed in 12.5%, and staghorn calculi in the presence of PHPT were identified in 17.7% of cases. Hypercalciuria in the group "with PHPT" was detected in 82.4% of patients (all 3 patients with staghorn calculi), and in the group "without PHPT"--in 18% of patients (2 of 21 patients with staghorn calculi). Hyperoxaluria was observed in 42.3% of patients "without PHPT" and in 35.3% of patients "with PHPT", in 36.8% of patients with simple stones and in 57.2%--with staghorn calculi. In 39% of patients "without PHPT", secondary hyperparathyroidism (SHPT) was diagnosed. SHPT prevalence was 28% in patients with staghorn calculi, and 45% in patients with simple stones. In 87.5% of patients with hypomagnesemia, staghorn calculi were observed. Significant relationship between magnesium and triglycerides (r(s) = -0.296; P = 0.041), and magnesium and high-density lipoproteins (r(s) = 0.339; P = 0.032) in all patients with urolithiasis were revealed. Thus, the study found no association between staghorn nephrolithiasis and PHPT. Elevated PTH levels usually indicate SHPT rather than PHPT. In hypocalcemia, there was more strong association between PTH and calcium, in normocalcaemia--between PTH and magnesium.}, }
@article {pmid26955544, year = {2014}, author = {Grases, F and Costa-Bauzá, A and Prieto, RM and Servera, A}, title = {Internalization of Calcium Oxalate Calculi Developed in Narrow Cavities.}, journal = {Urology case reports}, volume = {2}, number = {2}, pages = {51-53}, pmid = {26955544}, issn = {2214-4420}, abstract = {We describe the case of a patient with calcium oxalate monohydrate and calcium oxalate dihydrate calculi occluded in cavities. All those calculi were located inside narrow cavities covered with a thin epithelium that permits their visualization. Urinary biochemical analysis showed high calciuria, not hypercalciuria, hypocitraturia, and a ratio [calcium]/[citrate] >0.33. The existence of cavities of very low urodynamic efficacy was decisive in the formation of such calculi. It is important to emphasize that we observed a thin epithelium covering such cavities, demonstrating that this epithelium may be formed after the development of the calculi through a re-epithelialization process.}, }
@article {pmid24519664, year = {2014}, author = {Escribano, J and Balaguer, A and Roqué i Figuls, M and Feliu, A and Ferre, N}, title = {Dietary interventions for preventing complications in idiopathic hypercalciuria.}, journal = {The Cochrane database of systematic reviews}, volume = {}, number = {2}, pages = {CD006022}, doi = {10.1002/14651858.CD006022.pub4}, pmid = {24519664}, issn = {1469-493X}, mesh = {Adult ; Calcium, Dietary/administration &amp; dosage ; Diet, Protein-Restricted ; Diet, Sodium-Restricted ; Humans ; Hypercalciuria/complications/*diet therapy ; Hyperoxaluria/prevention &amp; control ; Nephrolithiasis/*diet therapy/prevention &amp; control ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Idiopathic hypercalciuria is an inherited metabolic abnormality that is characterised by excessive amounts of calcium excreted in the urine by people whose calcium serum levels are normal. Morbidity associated with idiopathic hypercalciuria is chiefly related to kidney stone disease and bone demineralisation leading to osteopenia and osteoporosis. Idiopathic hypercalciuria contributes to kidney stone disease at all life stages; people with the condition are prone to developing oxalate and calcium phosphate kidney stones. In some cases, crystallised calcium can be deposited in the renal interstitium, causing increased calcium levels in the kidneys. In children, idiopathic hypercalciuria can cause a range of comorbidities including recurrent macroscopic or microscopic haematuria, frequency dysuria syndrome, urinary tract infections and abdominal and lumbar pain. Various dietary interventions have been described that aim to decrease urinary calcium levels or urinary crystallisation.<br><br>OBJECTIVES: Our objectives were to assess the efficacy, effectiveness and safety of dietary interventions for preventing complications in idiopathic hypercalciuria (urolithiasis and osteopenia) in adults and children, and to assess the benefits of dietary interventions in decreasing urological symptomatology in children with idiopathic hypercalciuria.<br><br>SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register (23 April 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE.<br><br>SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs that investigated dietary interventions aimed at preventing complications of idiopathic hypercalciuria, compared with placebo, no intervention, or other dietary interventions regardless of route of administration, dose or amount.<br><br>DATA COLLECTION AND ANALYSIS: Studies were assessed for inclusion and data extracted using a standardised data extraction form. We calculated risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI).<br><br>MAIN RESULTS: We included five studies (379 adult participants) that investigated a range of interventions. Lack of similarity among interventions investigated meant that data could not be pooled. Overall, study methodology was not adequately reported in any of the included studies. There was a high risk of bias associated with blinding (although it seems unlikely that outcomes measures were unduly influenced by lack of intervention blinding), random sequence generation and allocation methodologies were unclear in most studies, but selective reporting bias was assessed as low.One study (120 participants) compared a low calcium diet with a normal calcium, low protein, low salt diet for five years. There was a significant decrease in numbers of new stone recurrences in those treated with the normal calcium, low protein, low salt diet (RR 0.77, 95% CI 0.61 to 0.98). This diet also led to a significant decrease in oxaluria (MD 78.00 &#xb5;mol/d, 95% CI 26.48 to 129.52) and the calcium oxalate relative supersaturation index (MD 1.20 95% CI 0.21 to 2.19).One study (210 participants) compared a low salt, normal calcium diet with a broad diet for three months. The low salt, normal calcium diet decreased urinary calcium (MD -45.00 mg/d, 95% CI -74.83 to -15.17) and oxalate excretion (MD -4.00 mg/d, 95% CI -6.44 to -1.56).A small study (17 participants) compared the effect of dietary fibre as part of a low calcium, low oxalate diet over three weeks, and found that although calciuria levels decreased, oxaluria increased. Phyllanthus niruri plant substrate intake was investigated in a small subgroup with hypercalciuria (20 participants); there was no significant effect on calciuria levels occurred after three months of treatment.A small cross-over study (12 participants) evaluating the changes in urinary supersaturation indices among patients who consumed calcium-fortified orange juice or milk for one month found no benefits for participants.None of the studies reported any significant adverse effects associated with the interventions.<br><br>AUTHORS' CONCLUSIONS: Long-term adherence (five years) to diets that feature normal levels of calcium, low protein and low salt may reduce numbers of stone recurrences, decrease oxaluria and calcium oxalate relative supersaturation indexes in people with idiopathic hypercalciuria who experience recurrent kidney stones. Adherence to a low salt, normal calcium level diet for some months can reduce calciuria and oxaluria. However, the other dietary interventions examined did not demonstrate evidence of significant beneficial effects.No studies were found investigating the effect of dietary recommendations on other clinical complications or asymptomatic idiopathic hypercalciuria.}, }
@article {pmid24470067, year = {2014}, author = {Smith, SM and Zwart, SR and Heer, M and Hudson, EK and Shackelford, L and Morgan, JL}, title = {Men and women in space: bone loss and kidney stone risk after long-duration spaceflight.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {29}, number = {7}, pages = {1639-1645}, doi = {10.1002/jbmr.2185}, pmid = {24470067}, issn = {1523-4681}, mesh = {Biomarkers/metabolism ; Bone Density ; Bone Resorption/*complications/*etiology/physiopathology/urine ; Calcium/metabolism ; *Extraterrestrial Environment ; Female ; Humans ; Kidney Calculi/*complications/*etiology/physiopathology/urine ; Male ; Risk Factors ; *Space Flight ; Time Factors ; }, abstract = {Bone loss, a key concern for long-duration space travelers, is typically considered a female issue. The number of women who have flown long-duration space missions is now great enough to allow a quantitative comparison of changes in bone and renal stone risk by sex. Participants were 42 astronauts (33 men and 9 women) on long-duration missions to the International Space Station. Bone mineral density (by dual-energy X-ray absorptiometry) and biochemical markers of bone metabolism (from blood and urine samples) were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. Missions were 49 to 215 days in duration, flown between 2000 and 2012. The bone density response to spaceflight was the same for men and women in both exercise groups. The bone mineral density response to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an advanced resistive exercise device. Biochemical markers of bone formation and resorption responded similarly in male and female astronauts. The response of urinary supersaturation risk to spaceflight was not significantly different between men and women, although risks were typically increased after flight in both groups, and risks were greater in men than in women before and after flight. The responses of men and women to spaceflight with respect to these measures of bone health were not different.}, }
@article {pmid24423579, year = {2014}, author = {Nouvenne, A and Ticinesi, A and Allegri, F and Guerra, A and Guida, L and Morelli, I and Borghi, L and Meschi, T}, title = {Twenty-five years of idiopathic calcium nephrolithiasis: has anything changed?.}, journal = {Clinical chemistry and laboratory medicine}, volume = {52}, number = {3}, pages = {337-344}, doi = {10.1515/cclm-2013-0618}, pmid = {24423579}, issn = {1437-4331}, mesh = {Adult ; Calcium/*metabolism ; Female ; Humans ; Internet ; Italy/epidemiology ; Kidney Calculi/*epidemiology/*metabolism/urine ; Life Style ; Male ; Risk ; Sex Factors ; }, abstract = {Idiopathic calcium nephrolithiasis (ICN) is a disease whose prevalence is rising. Our aim was to assess whether lifestyle indicators and habits of calcium stone formers in Italy have changed over the last 25 years, trying to establish a connection with the diffusion of Internet access. Therefore we examined the database of the Stone Clinic of Parma University Hospital and extracted 1952 (1192 M, 760 F) patients with ICN who underwent a full clinical and laboratory evaluation from 1986 to 2010. Laboratory evaluation included data on urinary 24-h volume, pH, sodium, potassium, chloride, calcium, phosphate, uric acid, magnesium, oxalate, and citrate. Patients were split in three groups on a chronological basis, according to official EUROSTAT-ISTAT data of Internet connection among families in Italy: Group 1, pre-Internet era (1986-1998, 853 patients); Group 2, narrow-band era (1999-2004, 467 patients); Group 3, broad-band era (2005-2010, 632 patients). Over the time we found a significant increase in water intake (1.37 vs. 1.78 L in men and 1.21 vs. 1.55 L in women, Group 1 vs. Group 3, p-trend<0.001) and a decrease in urinary sodium and chloride for both genders and calcium and magnesium only for males, while females experienced a slight increase in oxalate excretion. Supersaturation indexes for calcium and uric acid stones dramatically fell for both genders. The percentage of stone formers performing physical activity significantly rise (41% Group 3 vs. 8% Group 1, p<0.001) and we also found a trend of reduction in mean blood pressure. Therefore, the lifestyle of Italian idiopathic calcium stone formers has changed over the last 25 years, and the rising Internet access may have played a great role in driving this change.}, }
@article {pmid24296906, year = {2014}, author = {Shakhssalim, N and Basiri, A and Houshmand, M and Pakmanesh, H and Golestan, B and Azadvari, M and Aryan, H and Kashi, AH}, title = {Genetic polymorphisms in calcitonin receptor gene and risk for recurrent kidney calcium stone disease.}, journal = {Urologia internationalis}, volume = {92}, number = {3}, pages = {356-362}, doi = {10.1159/000353348}, pmid = {24296906}, issn = {1423-0399}, mesh = {3' Untranslated Regions ; Adult ; Calcium/blood/*metabolism/urine ; Case-Control Studies ; Chi-Square Distribution ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Introns ; Iran ; Kidney Calculi/*genetics/metabolism ; Male ; Middle Aged ; Odds Ratio ; Phenotype ; *Polymorphism, Single Nucleotide ; Receptors, Calcitonin/*genetics ; Recurrence ; Risk Factors ; }, abstract = {INTRODUCTION: In this study the full sequence of the calcitonin receptor gene (CALCR) in a group of Iranian males suffering from recurrent calcium urinary stones was compared with that of a control group.<br><br>METHODS: Serum and urinary biochemistry related to urolithiasis were evaluated in 105 males diagnosed with recurrent kidney calcium stones and 101 age-matched healthy control males. The polymerase chain reaction single-strand conformation polymorphism method was used to detect new polymorphisms in the CALCR.<br><br>RESULTS: Nine polymorphisms were detected; seven were in the non-coding and two in the coding region. The T allele associated with the 3'UTR+18C>T polymorphism was observed exclusively in the stone formers. The exact odds ratio for the T allele in this locus for those at risk of stone formation was 36.72 (95% CI 4.95-272.0) (p < 0.001). The mean (standard deviation) urine calcium concentration was 117 (60) mg/l in patients with the C allele and 152 (72) mg/l in those with the T allele (p = 0.03). In addition, IVS1-6T>C and IVS1insA polymorphisms in intron 1 were associated with kidney stone disease (p < 0.001). Regarding single nucleotide polymorphism 447, mean (standard deviation) of serum calcitonin levels were 16.7 (18.7) pg/ml, 10.5 (11.0) pg/ml and 9.94 (9.7) pg/ml in subjects with TT, TC and CC genotypes, respectively (p = 0.01).<br><br>CONCLUSION: Our data indicate a potential association between 3'UTR+18C>T and intron 1 polymorphisms in the CALCR and the risk of kidney stone disease.}, }
@article {pmid24218227, year = {2013}, author = {Panhwar, AH and Kazi, TG and Afridi, HI and Shaikh, HR and Arain, SA and Arain, SS and Brahman, KD}, title = {Evaluation of calcium and magnesium in scalp hair samples of population consuming different drinking water: risk of kidney stone.}, journal = {Biological trace element research}, volume = {156}, number = {1-3}, pages = {67-73}, doi = {10.1007/s12011-013-9850-1}, pmid = {24218227}, issn = {1559-0720}, mesh = {Adult ; *Calcium/administration &amp; dosage/adverse effects/analysis/metabolism ; *Drinking Water/adverse effects/analysis ; Female ; Hair/*metabolism ; Humans ; *Kidney Calculi/etiology/metabolism ; *Magnesium/administration &amp; dosage/adverse effects/analysis/metabolism ; Male ; Middle Aged ; Risk Factors ; Scalp/*metabolism ; }, abstract = {The objective of this study was to examine the relationship between calcium (Ca) and magnesium (Mg) in underground water (UGW), bottled mineral water (BMW), and domestic treated water (DTW) with related to risk of kidney stones. The water samples were collected from different areas of Sindh, Pakistan. The scalp hair samples of both genders, age ranged 30-60 years, consuming different types of water, have or have not kidney disorders, were selected. The Ca and Mg concentrations were determined in scalp hair of study subjects and water by flame atomic absorption spectroscopy. The Ca and Mg contents in different types of drinking water, UGW, DTW, and BMW, were found in the range of 79.1-466, 23.7-140, and 45-270 mg/L and 4.43-125, 5.23-39.6, and 7.16-51.3 mg/L, respectively. It was observed that Ca concentration in the scalp hair samples of kidney stone patients consuming different types of drinking water was found to be higher (2,895-4721 μg/g) while Mg level (84.3-101 μg/g) was lower as compare to referents subjects (2,490-2,730 μg/g for Ca, 107-128 μg/g for Mg) in both genders. The positive correlation was found between Ca and Mg levels in water with related to kidney stone formations in population, especially who consumed underground water. A relative risk and odd ratio were calculated; the relative risk had a strong positive association with incidence of kidney stone which depends on types of drinking water.}, }
@article {pmid24218027, year = {2014}, author = {Walker, V and Cook, P and Griffin, DG}, title = {Male hypercalciuric stone formers with low renal calcium reabsorption.}, journal = {Journal of clinical pathology}, volume = {67}, number = {4}, pages = {355-360}, doi = {10.1136/jclinpath-2013-201879}, pmid = {24218027}, issn = {1472-4146}, mesh = {Absorption ; Adult ; Aged ; Calcium/metabolism/*urine ; Cohort Studies ; Creatinine/*urine ; Cross-Sectional Studies ; Demography ; Humans ; Hypercalciuria/*urine ; Kidney/*metabolism ; Male ; Middle Aged ; Oxalates/urine ; Retrospective Studies ; Risk Factors ; Urolithiasis/*urine ; Young Adult ; }, abstract = {AIMS: Hypercalciuria is a common poorly understood abnormality among stone formers. We aimed to identify hypercalciuric male stone formers with a primary defect in renal calcium reabsorption and to look for associated risk factors.<br><br>METHODS: A retrospective cross-sectional database study of 623 male idiopathic calcium stone formers with normal plasma ultrafilterable calcium levels attending the Southampton stone clinic. Filtered calcium was estimated from plasma ultrafilterable calcium (60% of total plasma calcium) and 24 h creatinine clearance. Reabsorbed calcium was the difference between filtered and excreted calcium.<br><br>RESULTS: 276 men had hypercalciuria (urine calcium >7.50 mmol/24 h); 347 had normocalciuria. Hypercalciuric men filtered more calcium than normocalciuric men: median values 247 and 227 mmol/24 h, but the ranges overlapped (175-371 and 153-316 mmol/24 h). However, across the entire filtration range, hypercalciuric men reabsorbed less of the filtered calcium. Among the hypercalciuric men, we noticed differences between those with high and low filtration. We therefore compared data for hypercalciuric men in the highest and lowest filtration quintiles (n=55). Men with high filtration were younger at their first stone episode and had significantly higher plasma ultrafilterable calcium and calcium reabsorption, urinary calcium, oxalate, urate and creatinine excretion and creatinine clearance. 35% with high filtration and 40% with low filtration had recurrent stones; 27% and 20%, respectively, had an affected first-degree relative.<br><br>CONCLUSIONS: Hypercalciuric men reabsorbed proportionately less filtered calcium than normocalciuric men. Among hypercalciuric men, the risks for stones were higher in those with a high than a low filtered calcium load and presentation was earlier.}, }
@article {pmid24190699, year = {2014}, author = {Liu, W and Chen, M and Li, M and Ma, H and Tong, S and Lei, Y and Qi, L}, title = {Vitamin D receptor gene (VDR) polymorphisms and the urolithiasis risk: an updated meta-analysis based on 20 case-control studies.}, journal = {Urolithiasis}, volume = {42}, number = {1}, pages = {45-52}, pmid = {24190699}, issn = {2194-7236}, mesh = {Case-Control Studies ; Confidence Intervals ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Male ; Models, Genetic ; Odds Ratio ; *Polymorphism, Single Nucleotide ; Receptors, Calcitriol/*genetics ; Risk Factors ; Urolithiasis/*genetics ; }, abstract = {Vitamin D receptor (VDR) plays a key role in calcium metabolism, and is closely related to urinary stone formation (urolithiasis). Previous studies have investigated the associations between VDR single nucleotide polymorphisms (SNPs) (polymorphisms at BsmI, ApaI, FokI, or TaqI cutting sites) and urolithiasis in different populations. However, the results remain inconsistent and controversial. Therefore, meta-analysis was performed to evaluate these associations. Twenty studies that investigated the associations between VDR SNPs and urolithiasis were retrieved. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under the most appropriate genetic model. The TaqI polymorphism was associated with an increased risk of urolithiasis (tt + Tt vs. TT: OR = 1.253; 95% CI = 1.033-1.520, p = 0.022, I(2) = 0), whereas the ApaI, BsmI, and FokI polymorphisms were not. Stratifying for ethnicity, a slightly increased risk was found among Asians as compared to Whites (OR 1.263, 1.232, respectively, p < 0.01). Deviation from Hardy-Weinberg equilibrium (HWE) was the major source of heterogeneity. In summary, this updated meta-analysis suggests the TaqI polymorphism is associated with urolithiasis risk, whereas BsmI, ApaI, and FokI polymorphisms are not.}, }
@article {pmid24094983, year = {2013}, author = {Chen, Q and Zhang, Y and Tong, M and Wu, M and Snowise, S and Stone, P and Chamley, LW}, title = {Pre-treatment with calcium prevents endothelial cell activation induced by multiple activators, necrotic trophoblastic debris or IL-6 or preeclamptic sera: possible relevance to the pathogenesis of preeclampsia.}, journal = {Placenta}, volume = {34}, number = {12}, pages = {1196-1201}, doi = {10.1016/j.placenta.2013.09.014}, pmid = {24094983}, issn = {1532-3102}, mesh = {Calcium/*metabolism ; Calcium, Dietary/therapeutic use ; *Cell Communication ; Cell Line ; Cell-Free System ; Dietary Supplements ; Endothelium, Vascular/immunology/*metabolism ; Female ; Humans ; Interleukin-6/blood/genetics/*metabolism ; Necrosis ; Osmolar Concentration ; Placenta/blood supply/immunology/*metabolism/pathology ; Placental Circulation ; Pre-Eclampsia/immunology/*metabolism/pathology/prevention &amp; control ; Pregnancy ; Pregnancy Trimester, First ; Recombinant Proteins/metabolism ; Time Factors ; Tissue Culture Techniques ; }, abstract = {INTRODUCTION: A hallmark of preeclampsia is endothelial cell dysfunction/activation in response to "toxins" from the placenta. Necrotic trophoblastic debris (NTD) is one possible placental toxin and others include inflammatory cytokines. Calcium supplementation appears to protect "at-risk" women from developing preeclampsia by an unknown mechanism. In this study we investigate whether the addition of high levels of calcium to endothelial cells prior to their exposure to the preeclampsia-associated activators could reduce the endothelial cell activation.<br><br>METHODS: NTD was harvested from 1st trimester placental explants. Endothelial cells were treated with varied concentrations of calcium prior to exposure to NTD, IL-6 or preeclamptic sera or low levels of calcium. Activation was monitored by quantifying endothelial cell-surface ICAM-1 by ELISA or U937 adhesion to endothelial cells. The activity of endothelial cell nitric oxide synthetase was blocked with L-NAME.<br><br>RESULTS: Pre-treatment with increasing concentrations of calcium inhibited the activation of endothelial cells in response to NTD or IL-6 or preeclamptic sera. Inhibiting nitric oxide synthetase, using L-NAME, reduced the ability of high calcium levels to protect endothelial cell activation. Pre-treatment with calcium did not prevent endothelial cell activation induced by the reduction of the levels of calcium but additional calcium treatment did prevent endothelial cell activation induced by low calcium.<br><br>CONCLUSION: Our results demonstrate calcium supplementation may prevent the activation of the endothelium in response to activators. These results may partially explain the benefits of calcium supplementation in the reduction of risk for developing preeclampsia and provide in&#xa0;vitro mechanistic support for the use of calcium supplementation in at-risk women.}, }
@article {pmid23953243, year = {2014}, author = {Kirejczyk, JK and Porowski, T and Filonowicz, R and Kazberuk, A and Stefanowicz, M and Wasilewska, A and Debek, W}, title = {An association between kidney stone composition and urinary metabolic disturbances in children.}, journal = {Journal of pediatric urology}, volume = {10}, number = {1}, pages = {130-135}, doi = {10.1016/j.jpurol.2013.07.010}, pmid = {23953243}, issn = {1873-4898}, mesh = {Adolescent ; Calcium Oxalate/analysis ; Calcium Phosphates/analysis ; Child ; Female ; Humans ; Hydrogen-Ion Concentration ; Kidney Calculi/*chemistry ; Magnesium Compounds/analysis ; Male ; Phosphates/analysis ; Risk Factors ; Struvite ; }, abstract = {OBJECTIVE: To determine kidney stone composition in children and to correlate stone fractions with urinary pH and metabolic urinary risk factors.<br><br>PATIENTS AND METHODS: We studied 135 pediatric patients with upper urinary tract lithiasis in whom excreted or extracted stones were available for analyses. Composition of stones was analyzed. A 24-hour urine assessment included volume, pH and daily excretions of calcium, oxalate, uric acid, cystine, creatinine, phosphate, magnesium and citrate.<br><br>RESULTS: Calcium oxalate was the major component of 73% stones, followed by struvite (13%) and calcium phosphate (9%). Uric acid was present in almost half of stones, but in rudimentary amounts. The calcium oxalate content in calculi showed a strong relationship with calciuria, and moderate association with oxaluria, magnesuria and acidification of urine. The percent content of struvite presented reverse and lower correlations with regard to the above parameters. Calcium phosphate stone proportion had low associations with urinary risk factors.<br><br>CONCLUSIONS: Calciuria, oxaluria, magnesuria and low urine pH exerted the biggest influence on calcium oxalate content in pediatric renal stones. Relationships of urinary risk factors with calculi calcium phosphate content were of unclear significance. Urinary citrate excretion did not significantly correlate with kidney stone composition in children.}, }
@article {pmid23859700, year = {2013}, author = {Boyd, AS}, title = {Sialolith of a minor salivary gland.}, journal = {Journal of cutaneous pathology}, volume = {40}, number = {8}, pages = {695-698}, doi = {10.1111/cup.12191}, pmid = {23859700}, issn = {1600-0560}, mesh = {Aged ; Calcium/*metabolism ; Humans ; Male ; Salivary Ducts/metabolism/*pathology ; Salivary Gland Calculi/metabolism/*pathology ; Salivary Glands, Minor/metabolism/*pathology ; }, }
@article {pmid23822977, year = {2013}, author = {Chen, Q and Tong, M and Wu, M and Stone, PR and Snowise, S and Chamley, LW}, title = {Calcium supplementation prevents endothelial cell activation: possible relevance to preeclampsia.}, journal = {Journal of hypertension}, volume = {31}, number = {9}, pages = {1828-1836}, doi = {10.1097/HJH.0b013e328362ba1a}, pmid = {23822977}, issn = {1473-5598}, mesh = {Calcium/*administration &amp; dosage/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Cell Proliferation ; Cell Survival ; Culture Media ; Dietary Supplements ; Endothelial Cells/cytology/*drug effects ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Inflammation ; Interleukin-6/pharmacology ; Microcirculation ; NG-Nitroarginine Methyl Ester/pharmacology ; Necrosis ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/metabolism ; Placenta/metabolism ; Pre-Eclampsia/*metabolism/*pathology ; Pregnancy ; Trophoblasts/metabolism ; }, abstract = {OBJECTIVES: Preeclampsia is a leading cause of maternal and fetal mortality and morbidity. A hallmark of preeclampsia is endothelial cell dysfunction/activation in response to 'toxins' from the placenta. Necrotic trophoblastic debris (NTD) is one possible placental toxin and other activators of endothelial cells include inflammatory cytokines. Calcium supplementation appears to protect 'at-risk' women from developing preeclampsia but how is unclear.<br><br>METHODS: Placental explants were cultured with interleukin-6 (IL-6) in varied concentrations of calcium. The resultant trophoblastic debris was exposed to endothelial cells. Endothelial cells were exposed to activators including NTD, IL-6, and preeclamptic sera in the presence of varied concentrations of calcium and activation monitored by quantifying cell surface markers by ELISA.<br><br>RESULTS: Raising the levels of calcium did not prevent the IL-6-induced shedding of NTD from placental explants but did prevent the activation of endothelial cells in response to IL-6, preeclamptic sera, or NTD. Reducing the level of calcium directly induced the activation of endothelial cells. Inhibiting nitric oxide synthetase ablated the ability of high calcium levels to protect endothelial cell activation. The activity of endothelial cell nitric oxide synthetase was blocked with L-N-nitroarginine methyl ester.<br><br>CONCLUSION: Our results demonstrate calcium levels do not affect the shedding of trophoblastic debris but are important to endothelial cell activation and supplemental calcium may reverse the activation of the endothelium in preeclamptic women. These results may in part explain the benefits of calcium supplementation in the reduction of risk for developing preeclampsia and provide in-vitro mechanistic support for the use of calcium supplementation in at-risk women.}, }
@article {pmid23816746, year = {2013}, author = {Joshi, A and Gupta, SK and Srivastava, A}, title = {Metabolic evaluation in first-time renal stone formers in North India: a single center study.}, journal = {Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia}, volume = {24}, number = {4}, pages = {838-843}, doi = {10.4103/1319-2442.113916}, pmid = {23816746}, issn = {1319-2442}, mesh = {Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; India ; Kidney Calculi/*metabolism ; Male ; Middle Aged ; Young Adult ; }, abstract = {The risk of stone recurrence in first-time stone formers (FTSF) varies from 26% to 53%. There is no consensus regarding metabolic evaluation in these individuals. We evaluated the metabolic abnormalities in first-time renal stone forming patients in North India. Thirty-nine patients, (29 males and 10 females with mean age 39.3 ± 12.9 years) who presented with nephrolithiasis for the first time were evaluated. We evaluated the calcium homeostasis [serum corrected total calcium, phosphorous, creatinine, alkaline phosphatase, albumin, parathormone (iPTH), 25-hydroxy cholecalciferol (25(OH)D 3), 1-25 di-hydroxy cholecalciferol (1,25(OH) 2 D 3)] and performed the calcium load test also. Two 24-h urine collections were taken for citrate, oxalate, calcium and uric acid. Ammonium chloride loading test for diagnosis of distal renal tubular acidosis was performed in all patients. For each of the diagnostic categories, descriptive statistics were computed for all biochemical variables. A two-tailed P-value <0.05 was regarded as significant. Metabolic abnormalities were detected in 92.3% of the patients (n = 39) studied. Of them, almost 60% had two or more metabolic abnormalities. The most common metabolic abnormality was hypo-citraturia (82%), followed by hyper-oxaluria (56%) and hyper-calciuria (41%). Five percent of the patients had incomplete renal tubular acidosis, signifying the importance of the ammonium chloride loading test in patients with renal stones. None of the study patients were detected to have primary hyperparathyroidism. In three patients, the etiology could not be detected. Our findings suggest that an underlying disorder is present in majority of first-time renal stone formers. Intervention with appropriate treatment can prevent recurrences. Hence, comprehensive metabolic evaluation is recommended in all FTSF.}, }
@article {pmid23792498, year = {2013}, author = {Seager, CM and Srinivas, TR and Flechner, SM}, title = {Development of nephrolithiasis in a renal transplant patient during treatment with Cinacalcet.}, journal = {Annals of transplantation}, volume = {18}, number = {}, pages = {31-35}, doi = {10.12659/AOT.883809}, pmid = {23792498}, issn = {2329-0358}, mesh = {Adult ; Calcimimetic Agents/*adverse effects ; Calcium/metabolism ; Cinacalcet ; Humans ; Hypercalciuria/etiology ; Hyperparathyroidism, Secondary/drug therapy/etiology ; Kidney Failure, Chronic/complications/metabolism/surgery ; Kidney Transplantation/*adverse effects ; Male ; Naphthalenes/*adverse effects ; Nephrolithiasis/diagnostic imaging/*etiology ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Secondary hyperparathyroidism often accompanies chronic kidney disease, which can result in severe bone abnormalities and nephrolithiasis. Renal transplantation can correct the mineral abnormalities associated with chronic kidney disease, but one year after transplantation many recipients continue to exhibit persistent hyperparathyroidism.<br><br>CASE REPORT: Cinacalcet, a second-generation calcimimetic, has been shown to be effective in decreasing serum calcium levels in post kidney transplant patients with hyperparathyroidism. However a question remains whether patients with hyperparathyroidism who take Cinacalcet may be at increased risk of renal calcium deposits due to hypercalciuria and subsequent renal transplant dysfunction. We report the first well-documented case in which Cinacalcet contributed to the development of new renal calculi in a post-transplant patient with hyperparathyroidism (PTH 346 pg/mL), hypercalcemia (11.3 mg/dL), and good renal function (1.45 mg/dL). Interval imaging tracks the new onset of renal allograft stone formation after initiating Cinacalcet up to 60mg daily, which was accompanied by persistent hypercalciuria (478.2 mg/24 hours). The nephrolithiases resolved after discontinuing Cinacalcet and a subtotal parathyroidectomy.<br><br>CONCLUSIONS: This case supports the interval monitoring of urinary calcium excretion and imaging of the transplanted kidney for those recipients treated with Cinacalcet for hyperparathyroidism after renal transplantation.}, }
@article {pmid23739765, year = {2013}, author = {Tang, J and Chonchol, MB}, title = {Vitamin D and kidney stone disease.}, journal = {Current opinion in nephrology and hypertension}, volume = {22}, number = {4}, pages = {383-389}, doi = {10.1097/MNH.0b013e328360bbcd}, pmid = {23739765}, issn = {1473-6543}, support = {1R01DK081473-01/DK/NIDDK NIH HHS/United States ; 1R01DK094796/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; *Dietary Supplements/adverse effects ; Homeostasis ; Humans ; Kidney/*drug effects/metabolism ; Kidney Calculi/epidemiology/genetics/*metabolism ; Prevalence ; Risk Factors ; Treatment Outcome ; Vitamin D/adverse effects/metabolism/*therapeutic use ; Vitamin D Deficiency/*drug therapy/epidemiology/metabolism ; Vitamins/adverse effects/metabolism/*therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Vitamin D is important in maintaining calcium homeostasis, but its role in kidney stone disease and its effect on stone formation are still not clear.<br><br>RECENT FINDINGS: Kidney stone formers tend to experience enhanced intestinal calcium absorption, increased urinary calcium excretion, and excessive bone mineral loss. Although direct actions of active vitamin D have been implicated in all these processes, the effect of nutritional vitamin D (vitamin D2 or vitamin D3) use on calcium balance among stone formers is still not clear. In addition, the safety of nutritional vitamin D use in the stone forming population is also not established, considering the potential effect of its use on raising urinary calcium. However, most of the observational studies do not support a significant association between higher nutritional vitamin D store and increased risk of stone formation. Short-term nutritional vitamin D repletion in stone formers with vitamin D deficiency also does not appear to increase urinary calcium excretion.<br><br>SUMMARY: The effect of nutritional vitamin D use in stone formers is still not clear. As vitamin D deficiency is highly prevalent among stone formers, future prospective studies are needed to establish the biological effect, as well as the safety and efficacy of nutritional vitamin D therapy in this unique patient population.}, }
@article {pmid23674806, year = {2013}, author = {Weaver, CM}, title = {Potassium and health.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {4}, number = {3}, pages = {368S-77S}, pmid = {23674806}, issn = {2156-5376}, mesh = {Bone Density ; Bone Remodeling/physiology ; Calcium/metabolism ; Cardiovascular Diseases/metabolism ; Diet ; Humans ; Hypertension/*metabolism ; Kidney Diseases/metabolism ; Osteoporosis/*metabolism ; Potassium, Dietary/*metabolism ; Sodium, Dietary/metabolism ; Stroke/metabolism ; }, abstract = {Potassium was identified as a shortfall nutrient by the Dietary Guidelines for Americans 2010 Advisory Committee. The committee concluded that there was a moderate body of evidence of the association between potassium intake and blood pressure reduction in adults, which in turn influences the risk of stroke and coronary heart disease. Evidence is also accumulating of the protective effect of adequate dietary potassium on age-related bone loss and reduction of kidney stones. These benefits depend on organic anions associated with potassium as occurs in foods such as fruits and vegetables, in contrast to similar blood pressure-lowering benefits of potassium chloride. Benefits to blood pressure and bone health may occur at levels below current recommendations for potassium intake, especially from diet, but dose-response trials are needed to confirm this. Nevertheless, intakes considerably above current levels are needed for optimal health, and studies evaluating small increases in fruit and vegetable intake on bone and heart outcomes for short periods have had disappointing results. In modern societies, Western diets have led to a decrease in potassium intake with reduced consumption of fruits and vegetables with a concomitant increase in sodium consumption through increased consumption of processed foods. Consumption of white vegetables is associated with decreased risk of stroke, possibly related to their high potassium content. Potatoes are the highest source of dietary potassium, but the addition of salt should be limited. Low potassium-to-sodium intake ratios are more strongly related to cardiovascular disease risk than either nutrient alone. This relationship deserves further attention for multiple target tissue endpoints.}, }
@article {pmid23666418, year = {2013}, author = {Wolf, M and Bushinsky, DA}, title = {Innovations in bones and stones.}, journal = {Current opinion in nephrology and hypertension}, volume = {22}, number = {4}, pages = {369-370}, doi = {10.1097/MNH.0b013e3283622bd4}, pmid = {23666418}, issn = {1473-6543}, mesh = {Animals ; *Bone Remodeling/drug effects ; Bone and Bones/drug effects/*metabolism ; Calcium/*metabolism ; Dietary Supplements ; Homeostasis ; Humans ; Kidney Calculi/drug therapy/epidemiology/*metabolism ; Prognosis ; Risk Factors ; Vitamin D/therapeutic use ; Vitamin D Deficiency/drug therapy/metabolism ; Vitamins/therapeutic use ; }, }
@article {pmid23595293, year = {2013}, author = {Rendina, D and De Filippo, G and De Pascale, F and Zampa, G and Muscariello, R and De Palma, D and Ippolito, R and Strazzullo, P}, title = {The changing profile of patients with calcium nephrolithiasis and the ascendancy of overweight and obesity: a comparison of two patient series observed 25 years apart.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {28 Suppl 4}, number = {}, pages = {iv146-51}, doi = {10.1093/ndt/gft076}, pmid = {23595293}, issn = {1460-2385}, mesh = {Adult ; Biomarkers/*metabolism ; Body Mass Index ; Calcium/*metabolism ; Female ; Humans ; Male ; Nephrolithiasis/*etiology/*metabolism/pathology ; Obesity/*complications ; Overweight/*complications ; Oxalates/metabolism ; Uric Acid/metabolism ; }, abstract = {BACKGROUND: Epidemiological data indicate an increasing incidence and prevalence of nephrolithiasis (NL) worldwide in the last few decades.<br><br>METHODS: The aim of this study was to compare the clinical and biochemical profiles of recurrent stone formers referred to a Kidney Stone Centre from March 1983 to June 1986 with the one featured by patients seen 25 years later in the same geographical area, Campania, southern Italy.<br><br>RESULTS: Idiopathic calcium stone formers made up the large majority of the patient population in both series. Those examined in 2008-11 showed higher age at the onset of NL, higher prevalence of overweight/obesity and higher urinary excretion of oxalate and phosphate compared with those seen in 1983-86. The differences in the urinary biochemical variables remained significant upon accounting for age, gender, creatinine clearance and body mass index (BMI), and were not observed in patients with primary hyperparathyroidism enrolled in the same periods. A greater prevalence of uric acid stone formers was also observed in the 2008-11 population.<br><br>CONCLUSIONS: The massive epidemics of overweight/obesity and the substantial modifications of dietary habits over the last few decades in most Western countries may be the factors underlying the changing clinical and biochemical profiles of patients with recurrent NL.}, }
@article {pmid25167315, year = {2013}, author = {Sun, B and Duclos, G and Stone, HA}, title = {Network characteristics of collective chemosensing.}, journal = {Physical review letters}, volume = {110}, number = {15}, pages = {158103}, doi = {10.1103/PhysRevLett.110.158103}, pmid = {25167315}, issn = {1079-7114}, mesh = {Adenosine Triphosphate/*pharmacology ; Animals ; Calcium/metabolism ; Cell Communication/*drug effects/physiology ; Fibroblasts/*cytology/*drug effects/metabolism ; Gap Junctions/drug effects/metabolism ; Mice ; *Models, Biological ; NIH 3T3 Cells ; Poisson Distribution ; }, abstract = {The collective chemosensing of nonexcitable mammalian cells involves a biochemical network that features gap junction communications and heterogeneous single cell activities. To understand the integrated multicellular chemosensing, we study the calcium dynamics of micropatterned fibroblast cell colonies in response to adenosine triphosphate (ATP) stimulation. We find that the cross-correlation function between the responses of individual cells decays with topological distance as a power law for large colonies and much faster for smaller colonies. Furthermore, the strongly correlated cell pairs tend to form clusters and are more likely to exceed the percolation threshold. At a given topological distance, the cross-correlations exhibit characteristics of Poisson distributions, which allows us to estimate the unitary conductance of a single gap junction which is in good agreement with direct experimental measurements.}, }
@article {pmid23527052, year = {2013}, author = {Zachariou, M and Alexander, SP and Coombes, S and Christodoulou, C}, title = {A biophysical model of endocannabinoid-mediated short term depression in hippocampal inhibition.}, journal = {PloS one}, volume = {8}, number = {3}, pages = {e58926}, pmid = {23527052}, issn = {1932-6203}, mesh = {Algorithms ; Benzoxazines/pharmacology ; Biological Transport ; Calcium/metabolism ; Computer Simulation ; Depression/*metabolism ; Endocannabinoids/agonists/*metabolism ; Hippocampus/*metabolism ; Humans ; Models, Neurological ; Morpholines/pharmacology ; Naphthalenes/pharmacology ; *Neural Inhibition/drug effects ; Neurons/physiology ; Reproducibility of Results ; Signal Transduction ; Synaptic Transmission/drug effects ; Time Factors ; }, abstract = {Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread action on brain function through modulation of synaptic transmission and plasticity. Recent experimental studies have characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of short-term synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked. The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism both at synaptic and network level.}, }
@article {pmid23526577, year = {2013}, author = {Arrabal-Polo, MA and Arrabal-Martin, M and Arias-Santiago, S}, title = {Bone and metabolic markers in women with recurrent calcium stones.}, journal = {Korean journal of urology}, volume = {54}, number = {3}, pages = {177-182}, pmid = {23526577}, issn = {2005-6737}, abstract = {PURPOSE: The target of our work was to study several biochemical parameters in phospho-calcic and bone metabolism in blood and urine and the bone mineral density of women with recurrent calcium nephrolithiasis.<br><br>MATERIALS AND METHODS: We conducted a cross-sectional study with a control group of 85 women divided into 3 groups: group 1 consisted of 25 women without a history of nephrolithiasis, group 2 consisted of 35 women with only one episode of calcium nephrolithiasis, and group 3 consisted of 25 women with a history of recurrent calcium nephrolithiasis. Blood and urine biochemical study was performed, including markers related to lithiasis, and a bone mineral density study was done by use of bone densitometry.<br><br>RESULTS: Patients in group 3 showed statistically significantly elevated calciuria (15.4 mg/dL), fasting calcium/creatinine ratio (0.14), and 24-hour calcium/creatinine ratio (0.21) compared with groups 1 and 2. Moreover, this group of women with recurrent calcium nephrolithiasis had significantly elevated values of beta-crosslaps, a bone resorption marker, compared with groups 1 and 2 (p=0.000) and showed more bone mineral density loss than did these groups.<br><br>CONCLUSIONS: Recurrent calcium nephrolithiasis in women has a significant association with bone mineral density loss and with values of calciuria, both fasting and 24-hour.}, }
@article {pmid23507173, year = {2013}, author = {Whisner, CM and Martin, BR and Schoterman, MH and Nakatsu, CH and McCabe, LD and McCabe, GP and Wastney, ME and van den Heuvel, EG and Weaver, CM}, title = {Galacto-oligosaccharides increase calcium absorption and gut bifidobacteria in young girls: a double-blind cross-over trial.}, journal = {The British journal of nutrition}, volume = {110}, number = {7}, pages = {1292-1303}, doi = {10.1017/S000711451300055X}, pmid = {23507173}, issn = {1475-2662}, mesh = {Adolescent ; *Bifidobacterium ; Calcium/*metabolism/urine ; Calcium, Dietary/*metabolism/urine ; Child ; Double-Blind Method ; Feces/*microbiology ; Female ; Galactose/*pharmacology ; Humans ; Intestinal Absorption ; Intestines/*microbiology ; Oligosaccharides/*pharmacology ; }, abstract = {Adolescence is a time for rapid growth that represents an opportunity to influence peak bone mass. Prebiotic agents, such as galacto-oligosaccharides (GOS), increase Ca absorption in animal models and postmenopausal women. The objectives of the present study were to investigate the dose-response relationship of GOS supplementation on Ca absorption during growth and to assess changes in colonic microbiota to better understand the mechanism by which GOS is acting. A total of thirty-one healthy adolescent girls aged 10-13 years consumed smoothie drinks twice daily with 0, 2·5 or 5 g GOS for three 3-week periods in a random order. Fractional Ca absorption was determined from urinary Ca excretion over 48 h at the end of each 3-week period using a dual stable isotope method. Faecal microbiota and bifidobacteria were assessed by PCR-denaturing gradient gel electrophoresis and quantitative PCR. Fractional Ca absorption after the 48 h treatment with control, 5 and 10 g GOS/d was 0·393 (SD 0·092), 0·444 (SD 0·086) and 0·419 (SD 0·099), respectively. Significant improvements in Ca absorption were seen with both low and high doses of GOS compared with the control (P,0·02), but itwas not a dose-response relationship. The increase in absorption was greatest in the urine collected after 24 h, which is consistent with lower gut absorption. Faecal bifidobacteria increased (control 10·89 (SD 13·86), 5 g GOS 22·80 (SD 15·74) and 10 g GOS 11·54 (SD 14·20)) with the GOS treatment (P,0·03). The results suggest that daily consumption of 5 g GOS increases Ca absorption, which may be mediated by the gut microbiota, specifically bifidobacteria.}, }
@article {pmid23495759, year = {2013}, author = {Leani, JJ and Sánchez, HJ and Valentinuzzi, MC and Pérez, C and Grenón, MC}, title = {Qualitative microanalysis of calcium local structure in tooth layers by means of micro-RRS.}, journal = {Journal of microscopy}, volume = {250}, number = {2}, pages = {111-115}, doi = {10.1111/jmi.12026}, pmid = {23495759}, issn = {1365-2818}, mesh = {Calcium/*chemistry/metabolism ; Dental Calculus/*chemistry/ultrastructure ; Dental Enamel/*chemistry/ultrastructure ; Dentin/*chemistry/ultrastructure ; Fourier Analysis ; Humans ; Oxidation-Reduction ; *Software ; Spectrometry, X-Ray Emission/instrumentation/methods ; Spectrum Analysis, Raman/instrumentation/*methods ; Synchrotrons ; X-Rays ; }, abstract = {The Resonant inelastic X-ray scattering or resonant Raman scattering is an inelastic process of second order that becomes important when the energy of the excitation radiation is below but close to an absorption edge. In this process, the emitted photons have a continuous energy distribution with a high energy cut-off limit. In the last few years, experiments of resonant Raman scattering has become a very powerful technique to investigate excitations of electrons in solids. A qualitative study of the calcium local structure in the different layers of teeth was carried out. In order to perform the analysis, several measurements of tooth samples were achieved using monochromatic synchrotron radiation at the XRF station of the D09B-XRF beamline at the Brazilian synchrotron facility (LNLS, Campinas), below and close to the K absorption edge of Ca to inspect the resonant Raman scattering spectra. First of all, the spectra were analyzed with specific software to fit the experimental data. After that, the residuals were determined and a fast Fourier transform smoothing procedure was applied, taking into account the instrument functions of the detecting system. These oscillations present patterns that depend of the tooth layer, i.e. of the calcium state.}, }
@article {pmid23411066, year = {2013}, author = {Arrabal-Polo, M&#xc1; and Sierra Girón-Prieto, M and Orgaz-Molina, J and Zuluaga-Gómez, A and Arias-Santiago, S and Arrabal-Martín, M}, title = {Calcium renal lithiasis and bone mineral density. Importance of bone metabolism in urinary lithiasis.}, journal = {Actas urologicas espanolas}, volume = {37}, number = {6}, pages = {362-367}, doi = {10.1016/j.acuro.2012.10.003}, pmid = {23411066}, issn = {1699-7980}, mesh = {Biomarkers ; *Bone Density ; Bone Diseases, Metabolic/metabolism ; Bone Resorption/metabolism ; Bone and Bones/*metabolism ; Calcium/*metabolism ; Creatinine/blood ; Fasting/blood ; Humans ; Hypercalcemia/complications/congenital/metabolism ; Kidney Calculi/*metabolism ; Minerals/metabolism ; Nephrolithiasis/etiology/*metabolism ; Osteogenesis ; Osteoporosis/metabolism ; Phosphorus/metabolism ; }, abstract = {CONTEXT: Calcium Nephrolithiasis is a multifactorial disease; in its pathophysiology is involved various minerals and metabolic factors that may be altered, including bone and phosphor-calcium metabolism.<br><br>OBJECTIVE: To establish the scientific evidence and demonstrate the relationship between calcium nephrolithiasis and bone mineral density loss, through the use of bone turnover markers, serum and urinary metabolites.<br><br>EVIDENCE ACQUISITION: We performed a PubMed literature review using different MeSH Terms like "Nephrolithiasis", "Bone mineral density", "Urinary stones", "Calcium", Bone resorption" and "Bone formation", with different combinations. We only selected articles with abstracts in English or Spanish and discarded clinical cases and articles with inappropriate statistical study. A total of 40 articles were selected.<br><br>EVIDENCE SYNTHESIS: In different studies reviewed have been observed that patients with hypercalciuria have a higher bone mineral density loss with respect to normocalciuric. Among patients with calcium stones (normocalciuric or hypercalciuric), there is loss of bone mineral density, being more evident in patients with stones and hypercalciuria. This mineral density loss is marked and important in patients with recurrent calcium stones. Increased markers like fasting calcium/creatinine and &#x3b2;-CrossLaps are determinant of nephrolithiasis and mineral density loss in these patients.<br><br>CONCLUSION: We recommend perform markers of bone turnover and fasting calcium/creatinine in patients with recurrent calcium stones by the significant presence of bone mineral density loss, with a level of evidence III.}, }
@article {pmid23408426, year = {2013}, author = {Tan, JHY and Ludeman, JP and Wedderburn, J and Canals, M and Hall, P and Butler, SJ and Taleski, D and Christopoulos, A and Hickey, MJ and Payne, RJ and Stone, MJ}, title = {Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 (MCP-1).}, journal = {The Journal of biological chemistry}, volume = {288}, number = {14}, pages = {10024-10034}, pmid = {23408426}, issn = {1083-351X}, mesh = {Binding Sites ; Calcium/metabolism ; Chemokine CCL2/*metabolism ; Dimerization ; *Gene Expression Regulation ; HEK293 Cells ; Humans ; Kinetics ; Magnetic Resonance Spectroscopy/methods ; Mitogen-Activated Protein Kinase 3/metabolism ; Models, Chemical ; Peptides/chemistry ; Phosphorylation ; Protein Binding ; Protein Processing, Post-Translational ; Receptors, CCR2/*chemistry/physiology ; Sulfur/chemistry ; Tyrosine/*chemistry ; }, abstract = {Chemokine receptors are commonly post-translationally sulfated on tyrosine residues in their N-terminal regions, the initial site of binding to chemokine ligands. We have investigated the effect of tyrosine sulfation of the chemokine receptor CCR2 on its interactions with the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). Inhibition of CCR2 sulfation, by growth of expressing cells in the presence of sodium chlorate, significantly reduced the potency for MCP-1 activation of CCR2. MCP-1 exists in equilibrium between monomeric and dimeric forms. The obligate monomeric mutant MCP-1(P8A) was similar to wild type MCP-1 in its ability to induce leukocyte recruitment in vivo, whereas the obligate dimeric mutant MCP-1(T10C) was less effective at inducing leukocyte recruitment in vivo. In two-dimensional NMR experiments, sulfated peptides derived from the N-terminal region of CCR2 bound to both the monomeric and dimeric forms of wild type MCP-1 and shifted the equilibrium to favor the monomeric form. Similarly, MCP-1(P8A) bound more tightly than MCP-1(T10C) to the CCR2-derived sulfopeptides. NMR chemical shift mapping using the MCP-1 mutants showed that the sulfated N-terminal region of CCR2 binds to the same region (N-loop and β3-strand) of both monomeric and dimeric MCP-1 but that binding to the dimeric form also influences the environment of chemokine N-terminal residues, which are involved in dimer formation. We conclude that interaction with the sulfated N terminus of CCR2 destabilizes the dimerization interface of inactive dimeric MCP-1, thus inducing dissociation to the active monomeric state.}, }
@article {pmid23392537, year = {2013}, author = {Trinchieri, A}, title = {Diet and renal stone formation.}, journal = {Minerva medica}, volume = {104}, number = {1}, pages = {41-54}, pmid = {23392537}, issn = {0026-4806}, mesh = {Acids/metabolism ; Beverages ; Calcium/metabolism ; Calcium Oxalate/metabolism ; Calcium, Dietary/administration &amp; dosage/metabolism ; *Diet ; Dietary Proteins/administration &amp; dosage ; Drinking Water/administration &amp; dosage ; Fruit ; Humans ; Hyperoxaluria/etiology ; Kidney Calculi/*etiology/metabolism/prevention &amp; control ; Oxalates/administration &amp; dosage/metabolism ; Patient Education as Topic ; Secondary Prevention ; Sodium, Dietary/administration &amp; dosage/metabolism ; Vegetables ; }, abstract = {The relationship between diet and the formation of renal stones is demonstrated, but restrictive diets do not take into account the complexity of metabolism and the complex mechanisms that regulate the saturation and crystallization processes in the urine. The restriction of dietary calcium can reduce the urinary excretion of calcium but severe dietary restriction of calcium causes hyperoxaluria and a progressive loss of bone mineral component. Furthermore urinary calcium excretion is influenced by other nutrients than calcium as sodium, potassium, protein and refined carbohydrates. Up to 40% of the daily excretion of oxalate in the urine is from dietary source, but oxalate absorption in the intestine depends linearly on the concomitant dietary intake of calcium and is influenced by the bacterial degradation by several bacterial species of intestinal flora. A more rational approach should be based on the cumulative effects of foods and different dietary patterns on urinary saturation rather than on the effect of single nutrients. A diet based on a adequate intake of calcium (1000-1200 mg per day) and containment of animal protein and salt can decrease significantly urinary supersaturation for calcium oxalate and reduce the relative risk of stone recurrence in hypercalciuric renal stone formers. The DASH-style diet that is high in fruits and vegetables, moderate in low-fat dairy products and low in animal proteins and salt is associated with a lower relative supersaturation for calcium oxalate and a marked decrease in risk of incident stone formation. All the diets above mentioned have as a common characteristic the reduction of the potential acid load of the diet that can be correlated with a higher risk of recurrent nephrolithiasis, because the acid load of diet is inversely related to urinary citrate excretion. The restriction of protein and salt with an adequate calcium intake seem to be advisable but should be implemented with the advice to increase the intake of vegetables that can carry a plentiful supply of alkali that counteract the acid load coming from animal protein. New prospective studies to evaluate the effectiveness of the diet for the prevention of renal stones should be oriented to simple dietary advices that should be focused on a few specific goals easily controlled by means of self-evaluation tools, such as the LAKE food screener.}, }
@article {pmid23377289, year = {2013}, author = {Porowski, T and Kirejczyk, JK and Konstantynowicz, J and Kazberuk, A and Plonski, G and Wasilewska, A and Laube, N}, title = {Correspondence between Ca[2+] and calciuria, citrate level and pH of urine in pediatric urolithiasis.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {28}, number = {7}, pages = {1079-1084}, pmid = {23377289}, issn = {1432-198X}, mesh = {Adolescent ; Age Factors ; Biomarkers/urine ; Calcium/*urine ; Calcium Citrate/*urine ; Calcium Oxalate/urine ; Case-Control Studies ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Hydrogen-Ion Concentration ; Hypercalciuria/complications/diagnosis/*urine ; Male ; Predictive Value of Tests ; Risk Factors ; Urolithiasis/diagnosis/etiology/*urine ; }, abstract = {BACKGROUND: Hypercalciuria and hypocitraturia are considered the most important risk factors for urolithiasis. Citrate binds to urinary calcium to form a soluble complex which decreases the availability of ionized calcium (Ca(2+)) necessary for calcium oxalate formation and phosphate crystallization. The aims of this study were to assess the Ca(2+) fraction in relation to total calciuria, citraturia and urinary pH and to determine whether urinary Ca(2+) concentration is a helpful biomarker in metabolic evaluation of children with urolithiasis.<br><br>METHODS: We collected 24-h urine samples from 123 stone-forming children and adolescents with hypocitraturia and from 424 healthy controls. Total calciuria (total calcium, Catotal), Ca(2+), pH, citrate, oxalate and Bonn Risk Index (BRI) were assessed and compared between the two groups.<br><br>RESULTS: Total calciuria and Ca(2+) content were higher in stone-formers than in the healthy children. In both stone-formers and controls, Ca(2+) content was inversely related to citraturia and urinary pH, whereas the Ca(2+)/Catotal ratio differed slightly between the groups. A large variability in Ca(2+) level was found across individuals in both groups. The BRI increased with increasing calciuria and urine acidity.<br><br>CONCLUSIONS: Compared to controls, stone-formers with hypocitraturia demonstrated a higher urinary Ca(2+) concentration, but this was proportional to calciuria. The large individual variability in urinary Ca(2+) content limits its practical use in metabolic evaluation of children with urolithiasis. However, the Ca/Citrate ratio may be a useful clinical tool in evaluating children with urolithiasis.}, }
@article {pmid23375914, year = {2013}, author = {Arrabal-Polo, MA and Arias-Santiago, S and de Haro-Muñoz, T and Lopez-Ruiz, A and Orgaz-Molina, J and Gonzalez-Torres, S and Zuluaga-Gomez, A and Arrabal-Martin, M}, title = {Effects of aminobisphosphonates and thiazides in patients with osteopenia/osteoporosis, hypercalciuria, and recurring renal calcium lithiasis.}, journal = {Urology}, volume = {81}, number = {4}, pages = {731-737}, doi = {10.1016/j.urology.2012.12.013}, pmid = {23375914}, issn = {1527-9995}, mesh = {Alendronate/*therapeutic use ; Bone Density ; Bone Density Conservation Agents/*therapeutic use ; Bone Diseases, Metabolic/*drug therapy ; Calcium/analysis ; Female ; Humans ; Hydrochlorothiazide/therapeutic use ; Hypercalciuria/*drug therapy ; Kidney Calculi/chemistry ; Male ; Middle Aged ; Nephrolithiasis/*drug therapy ; Osteoporosis/drug therapy ; Prospective Studies ; Recurrence ; Sodium Chloride Symporter Inhibitors/*therapeutic use ; }, abstract = {OBJECTIVE: To analyze the effects of aminobisphosphonates and thiazides on renal lithogenic activity and bone mineral density in patients with recurring renal calcium lithiasis.<br><br>MATERIALS AND METHODS: A prospective cohort study with 3 years of clinical follow-up data was performed. The study included 2 groups of patients with recurring calcium lithiasis, hypercalciuria, and bone mineral density loss. Group 1 included 35 patients who underwent treatment with 70 mg/wk alendronate. Group 2 included 35 patients who underwent treatment with 50 mg/d hydrochlothiazide and 70&#xa0;mg/wk alendronate. Biochemical analysis was performed at baseline, 6 months, and 2 years, bone densitometry at baseline and 2 years, and clinical follow-up during the 3 years of treatment. The biochemical variables from the blood and urine samples, recurrent lithiasis, and bone mineral density were analyzed.<br><br>RESULTS: Age, sex, baseline biochemical markers, and bone density showed no differences between the 2&#xa0;treatment groups at the onset of treatment. After 2 years of treatment, group 1 showed a significant decrease in bone turnover markers and calciuria and significant improvement in bone mineral density. After 2 years of treatment, group 2 showed a decrease in calciuria and bone markers. At 2 years, the decrease in calciuria and the improvement in bone mineral density were greater in group 2 than in group 1, and the difference was statistically significant.<br><br>CONCLUSION: Aminobisphosphonates improve bone mineral density and slow lithogenic activity; however, administration of aminobisphosphonates in association with thiazides produced the same clinical effects and also reduced calciuria and improved bone mineral density.}, }
@article {pmid23275617, year = {2013}, author = {Michael, ES and Kuliopulos, A and Covic, L and Steer, ML and Perides, G}, title = {Pharmacological inhibition of PAR2 with the pepducin P2pal-18S protects mice against acute experimental biliary pancreatitis.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {304}, number = {5}, pages = {G516-26}, pmid = {23275617}, issn = {1522-1547}, support = {R01 DK091327/DK/NIDDK NIH HHS/United States ; R01-HL-64701/HL/NHLBI NIH HHS/United States ; R01-CA-104406/CA/NCI NIH HHS/United States ; R01-DK-091327/DK/NIDDK NIH HHS/United States ; }, mesh = {Acinar Cells/drug effects ; Animals ; Bile Acids and Salts/metabolism ; Biliary Tract Diseases/*prevention &amp; control ; Calcium/metabolism ; Calcium Signaling/drug effects ; Ceruletide/pharmacology ; Cholangiopancreatography, Endoscopic Retrograde ; Chymotrypsinogen/metabolism ; Coloring Agents ; Enzyme Activation/drug effects ; Enzyme Precursors/metabolism ; Gallstones/prevention &amp; control ; Indicators and Reagents ; Lipopeptides/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pancreatitis/*prevention &amp; control ; Propidium ; Receptor, PAR-2/*antagonists &amp; inhibitors ; Trypsinogen/metabolism ; }, abstract = {Pancreatic acinar cells express proteinase-activated receptor-2 (PAR2) that is activated by trypsin-like serine proteases and has been shown to exert model-specific effects on the severity of experimental pancreatitis, i.e., PAR2(-/-) mice are protected from experimental acute biliary pancreatitis but develop more severe secretagogue-induced pancreatitis. P2pal-18S is a novel pepducin lipopeptide that targets and inhibits PAR2. In studies monitoring PAR2-stimulated intracellular Ca(2+) concentration changes, we show that P2pal-18S is a full PAR2 inhibitor in acinar cells. Our in vivo studies show that P2pal-18S significantly reduces the severity of experimental biliary pancreatitis induced by retrograde intraductal bile acid infusion, which mimics injury induced by endoscopic retrograde cholangiopancreatography (ERCP). This reduction in pancreatitis severity is observed when the pepducin is given before or 2 h after bile acid infusion but not when it is given 5 h after bile acid infusion. Conversely, P2pal-18S increases the severity of secretagogue-induced pancreatitis. In vitro studies indicate that P2pal-18S protects acinar cells against bile acid-induced injury/death, but it does not alter bile acid-induced intracellular zymogen activation. These studies are the first to report the effects of an effective PAR2 pharmacological inhibitor on pancreatic acinar cells and on the severity of experimental pancreatitis. They raise the possibility that a pepducin such as P2pal-18S might prove useful in the clinical management of patients at risk for developing severe biliary pancreatitis such as occurs following ERCP.}, }
@article {pmid23247537, year = {2013}, author = {Krieger, NS and Bushinsky, DA}, title = {The relation between bone and stone formation.}, journal = {Calcified tissue international}, volume = {93}, number = {4}, pages = {374-381}, pmid = {23247537}, issn = {1432-0827}, support = {R01 AR046289/AR/NIAMS NIH HHS/United States ; R01 DK075462/DK/NIDDK NIH HHS/United States ; R01 DK 75462/DK/NIDDK NIH HHS/United States ; AR 46289/AR/NIAMS NIH HHS/United States ; }, mesh = {Absorption ; Animals ; Bone Density ; Bone Resorption ; Bone and Bones/*metabolism/physiopathology ; Calcium/metabolism ; Calcium Oxalate/metabolism/urine ; Calcium, Dietary/metabolism ; Disease Models, Animal ; Female ; Homeostasis ; Humans ; Hypercalciuria/*metabolism ; Kidney Calculi/*metabolism/physiopathology ; Kidney Tubules/metabolism ; Male ; Nephrolithiasis/*metabolism/physiopathology ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitriol/metabolism ; }, abstract = {Hypercalciuria is the most common metabolic abnormality found in patients with calcium-containing kidney stones. Patients with hypercalciuria often excrete more calcium than they absorb, indicating a net loss of total-body calcium. The source of this additional urinary calcium is almost certainly the skeleton, the largest repository of calcium in the body. Hypercalciuric stone formers exhibit decreased bone mineral density (BMD), which is correlated with the increase in urine calcium excretion. The decreased BMD also correlates with an increase in markers of bone turnover as well as increased fractures. In humans, it is difficult to determine the cause of the decreased BMD in hypercalciuric stone formers. To study the effect of hypercalciuria on bone, we utilized our genetic hypercalciuric stone-forming (GHS) rats, which were developed through successive inbreeding of the most hypercalciuric Sprague-Dawley rats. GHS rats excrete significantly more urinary calcium than similarly fed controls, and all the GHS rats form kidney stones while control rats do not. The hypercalciuria is due to a systemic dysregulation of calcium homeostasis, with increased intestinal calcium absorption, enhanced bone mineral resorption, and decreased renal tubule calcium reabsorption associated with an increase in vitamin D receptors in all these target tissues. We recently found that GHS rats fed an ample calcium diet have reduced BMD and that their bones are more fracture-prone, indicating an intrinsic disorder of bone not secondary to diet. Using this model, we should better understand the pathogenesis of hypercalciuria and stone formation in humans to ultimately improve the bone health of patients with kidney stones.}, }
@article {pmid23199000, year = {2012}, author = {Yatabe, MS and Yatabe, J and Takano, K and Murakami, Y and Sakuta, R and Abe, S and Sanada, H and Kimura, J and Watanabe, T}, title = {Effects of a high-sodium diet on renal tubule Ca2+ transporter and claudin expression in Wistar-Kyoto rats.}, journal = {BMC nephrology}, volume = {13}, number = {}, pages = {160}, pmid = {23199000}, issn = {1471-2369}, mesh = {Animals ; Calbindin 1 ; Calbindins ; Calcium/urine ; Calcium Channels/*biosynthesis ; Claudin-2/*biosynthesis ; Gene Expression Regulation ; Kidney Tubules/*metabolism ; Rats ; Rats, Inbred WKY ; S100 Calcium Binding Protein G/*biosynthesis ; Sodium Chloride, Dietary/*administration &amp; dosage/adverse effects ; Sodium-Calcium Exchanger/*biosynthesis ; TRPV Cation Channels/*biosynthesis ; }, abstract = {BACKGROUND: Urinary Ca2+ excretion increases with dietary NaCl. NaCl-induced calciuria may be associated with hypertension, urinary stone formation and osteoporosis, but its mechanism and long-term effects are not fully understood. This study examined alterations in the expressions of renal Ca2+ transporters, channels and claudins upon salt loading to better understand the mechanism of salt-induced urinary Ca2+ loss.<br><br>METHODS: Eight-week old Wistar-Kyoto rats were fed either 0.3% or 8% NaCl diet for 8 weeks. Renal cortical expressions of Na+/Ca2+ exchanger 1 (NCX1), Ca2+ pump (PCMA1b), Ca2+ channel (TRPV5), calbindin-D28k, and claudins (CLDN-2, -7, -8, -16 and -19) were analyzed by quantitative PCR, western blot and/or immunohistochemistry.<br><br>RESULTS: Fractional excretion of Ca2+ increased 6.0 fold with high-salt diet. Renal cortical claudin-2 protein decreased by approximately 20% with decreased immunological staining on tissue sections. Claudin-16 and -19 expressions were not altered. Renal cortical TRPV5, calbindin-D28k and NCX1 expressions increased 1.6, 1.5 and 1.2 fold, respectively.<br><br>CONCLUSIONS: Chronic high-salt diet decreased claudin-2 protein and increased renal TRPV5, calbindin-D28k, and NCX1. Salt loading is known to reduce the proximal tubular reabsorption of both Na+ and Ca2+. The reduction in claudin-2 protein expression may be partly responsible for the reduced Ca2+ reabsorption in this segment. The concerted upregulation of more distal Ca2+-transporting molecules may be a physiological response to curtail the loss of Ca2+, although the magnitude of compensation does not seem adequate to bring the urinary Ca2+ excretion down to that of the normal-diet group.}, }
@article {pmid23180343, year = {2013}, author = {Hou, J}, title = {The role of claudin in hypercalciuric nephrolithiasis.}, journal = {Current urology reports}, volume = {14}, number = {1}, pages = {5-12}, pmid = {23180343}, issn = {1534-6285}, support = {P30 DK079333/DK/NIDDK NIH HHS/United States ; R01 DK084059/DK/NIDDK NIH HHS/United States ; R01DK084059/DK/NIDDK NIH HHS/United States ; }, mesh = {Calcium/*metabolism ; Claudins/genetics/*physiology ; Genome-Wide Association Study ; Humans ; Hypercalciuria/genetics/*metabolism ; Nephrolithiasis/genetics/*metabolism ; Nephrons/*metabolism/physiology ; }, abstract = {Calcium nephrolithiasis is a common condition. Family-based genetic linkage studies and genome-wide association studies (GWASs) have uncovered a run of important candidate genes involved in renal Ca(++) disorders and kidney stone diseases. The susceptible genes include NKCC2, ROMK and ClCkb/Barttin that underlie renal salt excretion; claudin-14, -16 and -19 that underlie renal Ca(++) excretion; and CaSR that provides a sensing mechanism for the kidney to regulate salt, water and Ca(++) homeostasis. Biological and physiological analyses have revealed the cellular mechanism for transepithelial Ca(++) transport in the kidney that depends on the concerted action of these gene products. Although the individual pathogenic weight of the susceptible genes in nephrolithiasis remains unclear, perturbation of their expression or function compromises the different steps within the integrated pathway for Ca(++) reabsorption, providing a physiological basis for diagnosing and managing kidney stone diseases.}, }
@article {pmid23177631, year = {2013}, author = {Goldfarb, DS and Arowojolu, O}, title = {Metabolic evaluation of first-time and recurrent stone formers.}, journal = {The Urologic clinics of North America}, volume = {40}, number = {1}, pages = {13-20}, pmid = {23177631}, issn = {1558-318X}, support = {T32 GM007308/GM/NIGMS NIH HHS/United States ; U54-DK08390/DK/NIDDK NIH HHS/United States ; }, mesh = {Calcium/*metabolism ; Citric Acid/*metabolism ; Disease Progression ; Humans ; Kidney Calculi/*metabolism ; Recurrence ; Risk Factors ; }, abstract = {Evaluation of stone formers should include careful attention to medications, past medical history, social history, family history, dietary evaluation, occupation, and laboratory evaluation. Laboratory evaluation requires at least serum chemistries and urinalysis. Twenty-four-hour urine collections are most appropriate for patients with recurrent stones or complex medical histories. However, these collections may be appropriate for some first-time stone formers, including those with comorbidities or large stones. Although twin studies demonstrate that heritability accounts for at least 50% of the kidney stone phenotype, the responsible genes are not clearly identified, and so genetic testing is rarely indicated.}, }
@article {pmid23054957, year = {2012}, author = {Ryan, LE and Ing, SW}, title = {Idiopathic hypercalciuria and bone health.}, journal = {Current osteoporosis reports}, volume = {10}, number = {4}, pages = {286-295}, pmid = {23054957}, issn = {1544-2241}, mesh = {Bone Density ; Bone and Bones/metabolism ; Calcium/metabolism ; Cytokines/metabolism ; Humans ; Hypercalciuria/*complications/diagnosis/drug therapy/metabolism ; Intestinal Mucosa/metabolism ; Kidney Calculi/diagnosis/drug therapy/*etiology/metabolism ; Osteoporosis/diagnosis/drug therapy/*etiology/metabolism ; }, abstract = {Calcium is an important participant in many physiologic processes including coagulation, cell membrane transfer, hormone release, neuromuscular activation, and myocardial contraction. The body cooperates in a sophisticated web of hormonally mediated interactions to maintain stable extracellular calcium levels. Calcium is vital for skeletal mineralization, and perturbations in extracellular calcium may be corrected at the expense of bone strength and integrity. The aim of this review is to delineate our current understanding of idiopathic hypercalciuria in the context of bone health, specifically its definition, etiology, epidemiology, laboratory evaluation, and potential therapeutic management.}, }
@article {pmid22778254, year = {2012}, author = {Bandyopadhyay, BC and Swaim, WD and Sarkar, A and Liu, X and Ambudkar, IS}, title = {Extracellular Ca(2+) sensing in salivary ductal cells.}, journal = {The Journal of biological chemistry}, volume = {287}, number = {36}, pages = {30305-30316}, pmid = {22778254}, issn = {1083-351X}, support = {R03 DE019524/DE/NIDCR NIH HHS/United States ; /ImNIH/Intramural NIH HHS/United States ; DE 019524/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Biological Transport/genetics ; Calcium/*metabolism ; Cell Line ; Male ; Mice ; Receptors, Calcium-Sensing/genetics/*metabolism ; Salivary Duct Calculi/genetics/*metabolism/pathology ; Salivary Ducts/*metabolism/pathology ; TRPC Cation Channels/genetics/*metabolism ; }, abstract = {Ca(2+) is secreted from the salivary acinar cells as an ionic constituent of primary saliva. Ions such as Na(+) and Cl(-) get reabsorbed whereas primary saliva flows through the salivary ductal system. Although earlier studies have shown that salivary [Ca(2+)] decreases as it flows down the ductal tree into the oral cavity, ductal reabsorption of Ca(2+) remains enigmatic. Here we report a potential role for the G protein-coupled receptor, calcium-sensing receptor (CSR), in the regulation of Ca(2+) reabsorption by salivary gland ducts. Our data show that CSR is present in the apical region of ductal cells where it is co-localized with transient receptor potential canonical 3 (TRPC3). CSR is activated in isolated salivary gland ducts as well as a ductal cell line (SMIE) by altering extracellular [Ca(2+)] or by aromatic amino acid, L-phenylalanine (L-Phe, endogenous component of saliva), as well as neomycin. CSR activation leads to Ca(2+) influx that, in polarized cells grown on a filter support, is initiated in the luminal region. We show that TRPC3 contributes to Ca(2+) entry triggered by CSR activation. Further, stimulation of CSR in SMIE cells enhances the CSR-TRPC3 association as well as surface expression of TRPC3. Together our findings suggest that CSR could serve as a Ca(2+) sensor in the luminal membrane of salivary gland ducts and regulate reabsorption of [Ca(2+)] from the saliva via TRPC3, thus contributing to maintenance of salivary [Ca(2+)]. CSR could therefore be a potentially important protective mechanism against formation of salivary gland stones (sialolithiasis) and infection (sialoadenitis).}, }
@article {pmid22757744, year = {2013}, author = {Arrabal-Polo, MA and Arrabal-Martin, M and Arias-Santiago, S and Garrido-Gomez, J and Poyatos-Andujar, A and Zuluaga-Gomez, A}, title = {Importance of citrate and the calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis.}, journal = {BJU international}, volume = {111}, number = {4}, pages = {622-627}, doi = {10.1111/j.1464-410X.2012.11292.x}, pmid = {22757744}, issn = {1464-410X}, mesh = {Adult ; Biomarkers/analysis ; Bone Density ; Calcium/metabolism/*urine ; Calculi/*chemistry ; Citric Acid/metabolism/*urine ; Confidence Intervals ; Creatinine/urine ; Cross-Sectional Studies ; Decalcification, Pathologic/*physiopathology ; Female ; Humans ; Incidence ; Linear Models ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Nephrolithiasis/diagnosis/*epidemiology/*urine ; Odds Ratio ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Risk Assessment ; Severity of Illness Index ; Spain ; Urinalysis ; }, abstract = {UNLABELLED: Different studies have shown the importance of citrate in the formation of calcium stones. It has further been shown that the states of metabolic acidosis result in an increase in bone resorption and lower urinary citrate levels. Increasing the intake of citrate in these patients can reduce the lithogenic risk and improve bone mineral density (BMD), contributing to control of both diseases. The study shows the importance of citrate in patients with calcium stones and BMD loss. The deficit in citrate excretion is associated with a decrease in bone mineralization and increased β-crosslaps. A calcium : citrate ratio >0.25 in patients with calcium stones and loss of mineral density may predict severe lithogenic activity.<br><br>OBJECTIVE: To analyse the importance of urinary citrate and the urinary calcium : citrate ratio in patients with calcium renal lithiasis and severe lithogenesis compared with a control group of patients without lithiasis.<br><br>MATERIAL AND METHODS: A cross-sectional study of 115 patients in eastern Andalusia, Spain was conducted. The patients were divided into two groups: Group A: 56 patients aged 25-60 years without calcium renal lithiasis; Group B: 59 patients aged 25-60 years, presenting with calcium renal lithiasis and severe lithogenesis. The citrate levels and the calcium : citrate ratio in the patients' urine and the relationship of these two factors to lithiasic activity were analysed and compared.<br><br>RESULTS: In Group B, 32.2% of the patients presented with hypocitraturia, compared with 14.3% of the patients in Group A (P = 0.02). The urinary citrate levels were lower in Group B than in Group A (P = 0.001) and the calcium : citrate ratio was higher in Group B than in Group A (P = 0.005). The results suggest that a patient urinary calcium : citrate ratio > 0.25 indicates severe lithogenesis (with a sensitivity of 89% and a specificity of 57%). After linear regression analysis, we found that the urinary citrate level is an independent factor associated with the changes in bone densitometry T-score values of patients.<br><br>CONCLUSIONS: The patients with severe lithogenesis presented with hypocitraturia, which was associated with lower bone mineral density. The calcium : citrate ratio, which is linearly related to the bone resorption marker &#x3b2;-crosslaps, could be useful in evaluating the risk of severe lithogenesis when this ratio is >0.25.}, }
@article {pmid22732341, year = {2012}, author = {Cupisti, A and Farnesi, I and Armillotta, N and Francesca, F}, title = {Staghorn cystine stone in a 72-year-old recurrent calcium stone former.}, journal = {Clinical nephrology}, volume = {78}, number = {1}, pages = {76-80}, doi = {10.5414/cn107046}, pmid = {22732341}, issn = {0301-0430}, mesh = {Aged ; Calcium/*metabolism ; Cystine/*metabolism ; Cystinuria/*complications/diagnosis/genetics/metabolism/therapy ; Humans ; Kidney Calculi/diagnostic imaging/*etiology/metabolism/therapy ; Lithotripsy ; Male ; Nephrostomy, Percutaneous ; Recurrence ; Spectrophotometry, Infrared ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {This case deals with the first diagnosis of Type B cystinuria with cystine nephrolithiasis in a 72-year-old male. Cystinuria is an inherited disease that consists of congenital abnormalities of renal and intestinal transport of dibasic amino acids. It often leads to frequent recurrent stone formation. Cystine stones most frequently occur in the 1st through 3rd decades of life with a decreased incidence in old age. This case shows that the first diagnosis of cystinuria may be made even in the 8th decade, without any family history, and in a patient with a history of recurrent calcium stone disease. Therefore, the chance of cystinuria must be always considered, even in older calcium stone formers.}, }
@article {pmid22649959, year = {2012}, author = {Trinchieri, A}, title = {Development of a rapid food screener to assess the potential renal acid load of diet in renal stone formers (LAKE score).}, journal = {Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica}, volume = {84}, number = {1}, pages = {36-38}, pmid = {22649959}, issn = {1124-3562}, mesh = {Acid-Base Equilibrium ; Acids/*metabolism ; Calcium/*metabolism ; Diet Surveys ; *Energy Intake ; *Food Analysis ; Humans ; *Hydrogen-Ion Concentration ; Italy ; Kidney/*metabolism ; Kidney Calculi/diet therapy/*metabolism/prevention &amp; control ; Regression Analysis ; Risk Assessment ; Risk Factors ; Sampling Studies ; Surveys and Questionnaires/standards ; Urban Population ; }, abstract = {AIM OF THE STUDY: The potential renal acid load of foods (PRAL) has been proposed as a causative factor of renal stone format ion in patients with calcium stones. Evaluation of the dietary PRAL seems to be advisable to evaluate the lithogenic potential of the diet of the individual patient.<br><br>MATERIALS AND METHODS: On the basis of a dietary questionnaire administered to a sample of 75 renal stone formers living in the urban area of Milan (Northern Italy), we selected the most frequently reported foods for each of 11 categories: grains, meats, cured meats, eggs, cheeses, legumes, potatoes, vegetables, fruit and juices, milk and dairies and bread. The PRAL per 100 g of each food was calculated considering its mineral and protein composition, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. The PRAL/100 g of each main food category was then calculated considering the frequency of the most represented (up to six) foods in the respective food group and the PRAL/100 g of each food. Subsequently the PRAL/100 g value for each main food category was adjusted for the standard serving size. Finally, according to the value of the adjusted PRAL value a score was assigned to each group of foods and named as LAKE (Load of Acid to Kidney Evaluation) score.<br><br>RESULTS: The scores computed for grains, meats, cured meats, eggs, cheeses, legumes,potatoes, vegetables, fruit &amp; juices, milk &amp; dairies and bread were +2, +10, +6, +4, +10, -2, -10, -10, -10, +1 and +1, respectively. Two report forms were designed to allow a rapid collection of data about the intake of each food group. Time requested for filling the forms and to compute scores ranges from 2 to 4 minutes (report forms can be requested to a.trinchieri@ospedale.lecco.it).<br><br>CONCLUSION: LAKE score can be an useful and simple tool in order to evaluate the dietary PRAL and to suggest modifications to achieve its reduction for the prevention of calcium nephrolithiasis and other diseases.}, }
@article {pmid22640262, year = {2012}, author = {Chutipongtanate, S and Fong-ngern, K and Peerapen, P and Thongboonkerd, V}, title = {High calcium enhances calcium oxalate crystal binding capacity of renal tubular cells via increased surface annexin A1 but impairs their proliferation and healing.}, journal = {Journal of proteome research}, volume = {11}, number = {7}, pages = {3650-3663}, doi = {10.1021/pr3000738}, pmid = {22640262}, issn = {1535-3907}, mesh = {Animals ; Annexin A1/*metabolism ; Calcium/metabolism/*physiology ; Calcium Oxalate/*metabolism ; Cell Death ; Cell Movement ; *Cell Proliferation ; Cells, Cultured ; Dogs ; Kidney Tubules/*cytology ; Membrane Proteins/metabolism ; Models, Biological ; Protein Interaction Maps ; Protein Transport ; Proteome/metabolism ; }, abstract = {Hypercalciuria is associated with kidney stone formation and impaired renal function. However, responses of renal tubular cells upon exposure to high-calcium environment remain largely unknown. We thus performed a proteomic analysis of altered proteins in renal tubular cells induced by high-calcium and evaluated functional significance of these changes. MDCK cells were maintained with or without 20 mM CaCl(2) for 72 h. Cellular proteins were then analyzed by two-dimensional electrophoresis (2-DE) (n = 5 gels derived from 5 independent culture flasks per group). Spot matching and quantitative intensity analysis revealed 20 protein spots (from a total of 700) that were differentially expressed between the two groups. These altered proteins were then identified by Q-TOF-MS and MS/MS analyses, including those involved in calcium binding, protein synthesis, carbohydrate metabolism, lipid metabolism, cell proliferation, mitosis regulation, apoptosis, cell migration, oxidative stress, and ion transport. Protein network analysis and functional validation revealed that high-calcium-exposed cells had 36.5% increase in calcium oxalate monohydrate (COM) crystal-binding capacity. This functional change was consistent to the expression data in which annexin A1 (ANXA1), a membrane-associated calcium-binding protein, was markedly increased on the apical surface of high-calcium-exposed cells. Pretreatment with anti-ANXA1 antibody could neutralize this increasing crystal-binding capacity. Moreover, high-calcium exposure caused defects in cell proliferation and wound healing. These expression and functional data demonstrate the enhanced crystal-binding capacity but impaired cell proliferation and wound healing in renal tubular cells induced by high-calcium. Taken together, these phenomena may contribute, at least in part, to the pathogenic mechanisms of hypercalciuria-induced nephrolithiasis and impaired renal function. Our in vitro study offers several candidates for further targeted functional studies to confirm their relevance in hypercalciuria and kidney stone disease in vivo.}, }
@article {pmid22610870, year = {2011}, author = {Gyawali, PR and Joshi, BR and Gurung, CK}, title = {Correlation of calcium, phosphorus, uric acid and magnesium level in serum and 24 hours urine of patients with urolithiasis.}, journal = {Kathmandu University medical journal (KUMJ)}, volume = {9}, number = {34}, pages = {54-56}, doi = {10.3126/kumj.v9i2.6289}, pmid = {22610870}, issn = {1812-2078}, mesh = {Adult ; Calcium/*metabolism ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Magnesium/*metabolism ; Male ; Nepal/epidemiology ; Phosphorus/*metabolism ; Prevalence ; Prospective Studies ; Risk Factors ; Time Factors ; Uric Acid/*metabolism ; Urinalysis/*methods ; Urolithiasis/*blood/epidemiology/*urine ; }, abstract = {UNLABELLED: BAKCGROUND: Urinary stones disease is common pathology encountered in urological practice in Nepal. Supersaturated urine and its stagnation are well known facts for the development of urolithiasis. Metabolic disorders like hypercalciuria, hyperuricaemia, hypocitraturia are also responsible for formation of urolithiasis.<br><br>OBJECTIVE: The aim of this study was to identify the level of calcium, phosphorus, uric acid, and magnesium in the blood and urine of Nepalese patients with urinary stones.<br><br>METHODS: This study was conducted over a period of six months (From May to November 2010). It is a descriptive cross sectional study and quantitative method was used for analysis. Primary data were collected and utilized from 79 cases.<br><br>RESULTS: The prevalence of urolithiasis in male patients was 65.8% and 34.2% in female patients (p less than 0.05). Serum calcium in stone former and non-stone former was 8.3+/-1.2 and 7.5+/-1.5 (p less than 0.01) respectively. Serum phosphorus and uric acid in both groups were statistically not significant (p value 0.269 and 0.597 respectively) though in 24 hours urine of stone formers value of phosphorus was 447.9+/-182.4 but in non-stone formers it was 186.5+/-118.7 (p less than 0.001). Magnesium level in urine was 48.1+/-69.7 and 131.4+/-86.9 (p less than 0.001) respectively.<br><br>CONCLUSION: Higher level of calcium in serum was found in patients with urolithiasis in our population. Though phosphate level in blood serum was not different in the both groups but in urine phosphate and magnesium levels were significantly different.}, }
@article {pmid22566661, year = {2012}, author = {Sun, B and Lembong, J and Normand, V and Rogers, M and Stone, HA}, title = {Spatial-temporal dynamics of collective chemosensing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {109}, number = {20}, pages = {7753-7758}, pmid = {22566661}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/*metabolism ; Animals ; Biological Clocks/physiology ; Calcium/*metabolism ; Cell Communication/*physiology ; Cell Count ; Fibroblasts/*metabolism ; Gap Junctions/*physiology ; Hydrogel, Polyethylene Glycol Dimethacrylate ; Image Processing, Computer-Assisted ; Mice ; Microscopy, Fluorescence ; NIH 3T3 Cells ; }, abstract = {Although the process of chemosensing by individual cells is intrisically stochastic, multicellular organisms exhibit highly regulated responses to external stimulations. Two key elements to understand the deterministic features of chemosensing are intercellular communications and the role of pacemaker cells. To characterize the collective behavior induced by these two factors, we study the spatial-temporal calcium dynamics of fibroblast cells in response to ATP stimulation. We find that closely packed cell colonies exhibit faster, more synchronized, and highly correlated responses compared to isolated cells. In addition, we demonstrate for chemosensing the existence of pacemaker cells and how the presence of gap junctions impact the first step of the collective response. By further comparing these results with the calcium dynamics of cells embedded in thin hydrogel films, where intercellular communication is only possible via diffusing molecules, we conclude that gap junctions are required for synchronized and highly correlated responses among cells in high density colonies. In addition, in high density cell colonies, both communication channels lead to calcium oscillations following the stimulation by external ATP. While the calcium oscillations associated with cells directly exposed to external flows were transient, the oscillations of hydrogel trapped cells can persist with a fundamental frequency and higher harmonics. Our observations and measurements highlight the crucial role of intercellular signaling for generating regulated spatial and temporal dynamics in cell colonies and tissues.}, }
@article {pmid22454531, year = {2012}, author = {Oliveira, AG and Aquino, DJ and Mahecha, GA and Oliveira, CA}, title = {Involvement of the transepithelial calcium transport disruption and the formation of epididymal stones in roosters.}, journal = {Reproduction (Cambridge, England)}, volume = {143}, number = {6}, pages = {835-844}, doi = {10.1530/REP-12-0034}, pmid = {22454531}, issn = {1741-7899}, mesh = {Animals ; Biological Transport/physiology ; Calcium/metabolism/physiology ; Calcium Signaling/*physiology ; Calcium-Binding Proteins/metabolism/physiology ; *Chickens/metabolism/physiology ; Epididymis/*pathology ; Male ; Models, Biological ; Plasma Membrane Calcium-Transporting ATPases/metabolism/physiology ; Poultry Diseases/*etiology/metabolism/pathology ; Sodium-Calcium Exchanger/metabolism/physiology ; TRPV Cation Channels/metabolism/physiology ; Urolithiasis/*etiology/metabolism/pathology/veterinary ; Urothelium/*metabolism/pathology ; }, abstract = {Epididymal lithiasis is a dysfunction of unknown origin characterized by the formation of calcium stones into the lumen of efferent ductules of roosters. Affected animals present an imbalance in the hormonal responsive systems that regulate the expression of proteins involved in the transepithelial calcium transport, as TRPV6, CaBP-D28K, NCX1, and PMCA. Because the efferent ductules are the major site of fluid and calcium reabsorption in excurrent ducts, it was hypothesized that impairment in local calcium homeostasis would lead to lithiasis. To test this hypothesis, we addressed the expression of these proteins in the epididymal region of affected animals. The present study focused on the investigation of the occurrence, tissue distribution, and physiological impact of the transepithelial calcium transport in roosters under normal and pathological conditions. The results showed that affected roosters presented a significant increase in TRPV6 and CaBP-D28k levels, whereas NCX1 and PMCA were not changed. Such alterations were more conspicuous in the proximal efferent ductules, in which was also observed accumulation of calcium within the epithelial cells. These findings provided the first evidences for the involvement of alteration in the expression of proteins essential for calcium reabsorption as a plausible mechanism for the formation of calcium stones within efferent ductules.}, }
@article {pmid22449672, year = {2012}, author = {Yasuda, K and Sasaki, K and Yamato, M and Rakugi, H and Isaka, Y and Hayashi, T}, title = {A case of nephrocalcinosis associated with primary aldosteronism.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {51}, number = {6}, pages = {625-627}, doi = {10.2169/internalmedicine.51.6543}, pmid = {22449672}, issn = {1349-7235}, mesh = {Adrenal Cortex Neoplasms/metabolism/surgery ; Adrenocortical Adenoma/metabolism/surgery ; Adult ; Calcium/*metabolism ; Calcium Phosphates/analysis ; Diagnosis, Differential ; Humans ; Hyperaldosteronism/*complications/diagnosis ; Hypertension/complications ; Kidney Calculi/chemistry ; Kidney Glomerulus/pathology ; Male ; Nephrocalcinosis/*etiology/pathology ; Nephrolithiasis/*etiology ; Tomography, X-Ray Computed ; }, abstract = {Herein, we report a 37-year-old man presenting with nephrocalcinosis associated with primary aldosteronism. Primary hyperaldosteronism is reported to facilitate urinary calcium excretion; however, renal calculi or calcinosis in this disorder has been rarely reported. The patient had renal dysfunction and calcification in the renal medulla on both kidneys. A kidney biopsy was performed. His renal dysfunction seemed to be mainly caused by hypertension and tubulointerstitial damage. Furthermore, von Kossa-positive stones were seen in some tubules. X-ray element analysis revealed that the stones were composed of calcium phosphate.}, }
@article {pmid22447589, year = {2012}, author = {Rodriguez-Navarro, C and Jroundi, F and Schiro, M and Ruiz-Agudo, E and González-Muñoz, MT}, title = {Influence of substrate mineralogy on bacterial mineralization of calcium carbonate: implications for stone conservation.}, journal = {Applied and environmental microbiology}, volume = {78}, number = {11}, pages = {4017-4029}, pmid = {22447589}, issn = {1098-5336}, mesh = {Bacteria/growth &amp; development/*metabolism ; Calcium/chemistry/metabolism ; Calcium Carbonate/*metabolism ; Construction Materials/analysis/*microbiology ; Microscopy, Atomic Force ; Microscopy, Electron, Scanning ; Minerals/*chemistry/metabolism ; Myxococcus xanthus/growth &amp; development/metabolism ; Silicates/chemistry/metabolism ; Substrate Specificity ; X-Ray Diffraction ; }, abstract = {The influence of mineral substrate composition and structure on bacterial calcium carbonate productivity and polymorph selection was studied. Bacterial calcium carbonate precipitation occurred on calcitic (Iceland spar single crystals, marble, and porous limestone) and silicate (glass coverslips, porous sintered glass, and quartz sandstone) substrates following culturing in liquid medium (M-3P) inoculated with different types of bacteria (Myxococcus xanthus, Brevundimonas diminuta, and a carbonatogenic bacterial community isolated from porous calcarenite stone in a historical building) and direct application of sterile M-3P medium to limestone and sandstone with their own bacterial communities. Field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), powder X-ray diffraction (XRD), and 2-dimensional XRD (2D-XRD) analyses revealed that abundant highly oriented calcite crystals formed homoepitaxially on the calcitic substrates, irrespective of the bacterial type. Conversely, scattered spheroidal vaterite entombing bacterial cells formed on the silicate substrates. These results show that carbonate phase selection is not strain specific and that under equal culture conditions, the substrate type is the overruling factor for calcium carbonate polymorph selection. Furthermore, carbonate productivity is strongly dependent on the mineralogy of the substrate. Calcitic substrates offer a higher affinity for bacterial attachment than silicate substrates, thereby fostering bacterial growth and metabolic activity, resulting in higher production of calcium carbonate cement. Bacterial calcite grows coherently over the calcitic substrate and is therefore more chemically and mechanically stable than metastable vaterite, which formed incoherently on the silicate substrates. The implications of these results for technological applications of bacterial carbonatogenesis, including building stone conservation, are discussed.}, }
@article {pmid22427523, year = {2012}, author = {Benoist, D and Stones, R and Drinkhill, MJ and Benson, AP and Yang, Z and Cassan, C and Gilbert, SH and Saint, DA and Cazorla, O and Steele, DS and Bernus, O and White, E}, title = {Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {302}, number = {11}, pages = {H2381-95}, pmid = {22427523}, issn = {1522-1539}, support = {G0701785/MRC_/Medical Research Council/United Kingdom ; G0900524/MRC_/Medical Research Council/United Kingdom ; G900524/MRC_/Medical Research Council/United Kingdom ; RG/11/10/28924/BHF_/British Heart Foundation/United Kingdom ; PG/08/027/24774/BHF_/British Heart Foundation/United Kingdom ; G0701776/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Action Potentials/physiology ; Animals ; Arrhythmias, Cardiac/*physiopathology ; Calcium/metabolism ; Calcium-Transporting ATPases/metabolism ; Electrocardiography ; Heart Failure/*etiology/*physiopathology ; Hypertension, Pulmonary/*complications ; Male ; Models, Animal ; Myocytes, Cardiac/pathology ; Rats ; Rats, Wistar ; Sarcoplasmic Reticulum/metabolism ; Ventricular Dysfunction, Right/*physiopathology ; }, abstract = {Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca(2+) handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca(2+) transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca(2+)-ATPase activity, increased sarcoplasmic reticular Ca(2+)-release fraction, and increased Ca(2+) spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca(2+) handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs.}, }
@article {pmid22403735, year = {2012}, author = {Procino, G and Mastrofrancesco, L and Tamma, G and Lasorsa, DR and Ranieri, M and Stringini, G and Emma, F and Svelto, M and Valenti, G}, title = {Calcium-sensing receptor and aquaporin 2 interplay in hypercalciuria-associated renal concentrating defect in humans. An in vivo and in vitro study.}, journal = {PloS one}, volume = {7}, number = {3}, pages = {e33145}, pmid = {22403735}, issn = {1932-6203}, support = {GGP04202/TI_/Telethon/Italy ; }, mesh = {Absorption/drug effects ; Animals ; Aquaporin 2/*metabolism ; Calcium/metabolism/urine ; Cell Line ; Cell Membrane/drug effects/metabolism ; Child ; Colforsin/pharmacology ; Cyclic AMP/metabolism ; Diuresis/drug effects ; Extracellular Space/drug effects/metabolism ; Female ; Humans ; Hypercalciuria/*metabolism/pathology ; Kidney/drug effects/*metabolism ; Male ; Mice ; Osmolar Concentration ; Protein Transport/drug effects ; Receptors, Calcium-Sensing/agonists/*metabolism ; Signal Transduction/drug effects ; Time Factors ; Vasopressins/metabolism ; Water/metabolism ; rhoA GTP-Binding Protein/metabolism ; }, abstract = {One mechanism proposed for reducing the risk of calcium renal stones is activation of the calcium-sensing receptor (CaR) on the apical membranes of collecting duct principal cells by high luminal calcium. This would reduce the abundance of aquaporin-2 (AQP2) and in turn the rate of water reabsorption. While evidence in cells and in hypercalciuric animal models supports this hypothesis, the relevance of the interplay between the CaR and AQP2 in humans is not clear. This paper reports for the first time a detailed correlation between urinary AQP2 excretion under acute vasopressin action (DDAVP treatment) in hypercalciuric subjects and in parallel analyzes AQP2-CaR crosstalk in a mouse collecting duct cell line (MCD4) expressing endogenous and functional CaR. In normocalciurics, DDAVP administration resulted in a significant increase in AQP2 excretion paralleled by an increase in urinary osmolality indicating a physiological response to DDAVP. In contrast, in hypercalciurics, baseline AQP2 excretion was high and did not significantly increase after DDAVP. Moreover DDAVP treatment was accompanied by a less pronounced increase in urinary osmolality. These data indicate reduced urinary concentrating ability in response to vasopressin in hypercalciurics. Consistent with these results, biotinylation experiments in MCD4 cells revealed that membrane AQP2 expression in unstimulated cells exposed to CaR agonists was higher than in control cells and did not increase significantly in response to short term exposure to forskolin (FK). Interestingly, we found that CaR activation by specific agonists reduced the increase in cAMP and prevented any reduction in Rho activity in response to FK, two crucial pathways for AQP2 translocation. These data support the hypothesis that CaR-AQP2 interplay represents an internal renal defense to mitigate the effects of hypercalciuria on the risk of calcium precipitation during antidiuresis. This mechanism and possibly reduced medulla tonicity may explain the lower concentrating ability observed in hypercalciuric patients.}, }
@article {pmid22361283, year = {2012}, author = {Powers, JG and Gilchrest, BA}, title = {What you and your patients need to know about vitamin D.}, journal = {Seminars in cutaneous medicine and surgery}, volume = {31}, number = {1}, pages = {2-10}, doi = {10.1016/j.sder.2011.11.008}, pmid = {22361283}, issn = {1558-0768}, mesh = {Age Factors ; Calcium/metabolism/therapeutic use ; Dietary Supplements ; Homeostasis ; Humans ; Immunity ; Musculoskeletal Physiological Phenomena ; Neoplasms/prevention &amp; control ; Nutrition Policy ; Prospective Studies ; Sex Factors ; Sunlight ; Sunscreening Agents/pharmacology ; Ultraviolet Rays ; Vitamin D/blood/*physiology/therapeutic use ; Vitamin D Deficiency/complications/therapy ; Vitamins/therapeutic use ; }, abstract = {"Vitamin D" is the term commonly used to denote the lipid-soluble hormone critical for calcium homeostasis and skeletal maintenance. A precursor to the active compound is found in many plants and animal tissues and can be absorbed from the gut; it can also be derived from cell membranes in the epidermis during ultraviolet B irradiation. This compound is then hydroxylated sequentially in the liver and kidney to produce the active hormone 1,25(OH)(2)D that binds its nuclear receptor to modulate gene expression. Recently, vitamin D hydroxylases and the nuclear receptor have been identified in many tissues, suggesting previously unrecognized roles for vitamin D. Some epidemiologic studies have also correlated low levels of the inactive storage form 25(OH)D with an increased incidence or prevalence of a variety of diseases, suggesting that large oral supplements and/or increased ultraviolet (UV) exposure might therefore improve individual health. However, randomized, prospective controlled trials comparing vitamin D supplements with placebo have not supported this belief. Moreover, current evidence supports the conclusion that protection from UV radiation does not compromise vitamin D status or lead to iatrogenic disease. In contrast, high vitamin D levels appear to incur a risk of kidney stones and other adverse effects. In the case of true vitamin D deficiency, supplements are a more reliable and quantifiable source of the vitamin than UV exposure.}, }
@article {pmid22352355, year = {2012}, author = {Rossi, F and Micheletti, E and Bruno, L and Adhikary, SP and Albertano, P and Philippis, RD}, title = {Characteristics and role of the exocellular polysaccharides produced by five cyanobacteria isolated from phototrophic biofilms growing on stone monuments.}, journal = {Biofouling}, volume = {28}, number = {2}, pages = {215-224}, doi = {10.1080/08927014.2012.663751}, pmid = {22352355}, issn = {1029-2454}, mesh = {Biofilms/*growth &amp; development ; *Biofouling ; Calcium/metabolism ; Chlorophyll/metabolism ; Chlorophyll A ; Cyanobacteria/isolation &amp; purification/metabolism/*physiology/radiation effects ; Ferrous Compounds/metabolism ; India ; Indoles/metabolism ; Magnesium/metabolism ; Minerals/metabolism ; Phenols/metabolism ; Phototrophic Processes ; Pigments, Biological/metabolism ; *Polysaccharides, Bacterial/chemistry/isolation &amp; purification/physiology ; Ultraviolet Rays ; }, abstract = {Three coccoid and two filamentous cyanobacterial strains were isolated from phototrophic biofilms exposed to intense solar radiation on lithic surfaces of the Parasurameswar Temple and Khandagiri caves, located in Orissa State, India. Based on to their morphological features, the three coccoid strains were assigned to the genera Gloeocapsosis and Gloeocapsa, while the two filamentous strains were assigned to the genera Leptolyngbya and Plectonema. Eleven to 12 neutral and acidic sugars were detected in the slime secreted by the five strains. The secretions showed a high affinity for bivalent metal cations, suggesting their ability to actively contribute to weakening the mineral substrata. The secretion of protective pigments in the polysaccharide layers, namely mycosporine amino acid-like substances (MAAs) and scytonemins, under exposure to UV radiation showed how the acclimation response contributes to the persistence of cyanobacteria on exposed lithoid surfaces in tropical areas.}, }
@article {pmid22341269, year = {2012}, author = {Sorensen, MD and Eisner, BH and Stone, KL and Kahn, AJ and Lui, LY and Sadetsky, N and Stoller, ML}, title = {Impact of calcium intake and intestinal calcium absorption on kidney stones in older women: the study of osteoporotic fractures.}, journal = {The Journal of urology}, volume = {187}, number = {4}, pages = {1287-1292}, pmid = {22341269}, issn = {1527-3792}, support = {R01 AR035583/AR/NIAMS NIH HHS/United States ; AR35582/AR/NIAMS NIH HHS/United States ; R01 AR035584/AR/NIAMS NIH HHS/United States ; AG05394/AG/NIA NIH HHS/United States ; R01 AG027576/AG/NIA NIH HHS/United States ; 2 R01 AG027574-22A1/AG/NIA NIH HHS/United States ; R01 AG005407/AG/NIA NIH HHS/United States ; R01 AR035582/AR/NIAMS NIH HHS/United States ; R01 AG005394/AG/NIA NIH HHS/United States ; AR35584/AR/NIAMS NIH HHS/United States ; R01 AG027574/AG/NIA NIH HHS/United States ; 2 R01 AG005394-22A1/AG/NIA NIH HHS/United States ; AG05407/AG/NIA NIH HHS/United States ; R01 AG027576-22/AG/NIA NIH HHS/United States ; AR35583/AR/NIAMS NIH HHS/United States ; }, mesh = {Aged ; Calcium/*metabolism ; Calcium, Dietary/*administration &amp; dosage/*metabolism ; Female ; Humans ; *Intestinal Absorption ; Kidney Calculi/*epidemiology/*metabolism ; Osteoporotic Fractures/metabolism ; Prospective Studies ; }, abstract = {PURPOSE: Intestinal calcium absorption is thought to have a critical role in nephrolithiasis. However, to our knowledge no study has directly assessed this association. Therefore, we explored the relationship among intestinal fractional calcium absorption, calcium intake and nephrolithiasis.<br><br>MATERIALS AND METHODS: The Study of Osteoporotic Fractures is a prospective cohort of 9,704 postmenopausal women recruited from population based listings in 1986 and followed for more than 20 years. Secondary analyses were performed of 7,982 women who reported their history of nephrolithiasis, of which 5,452 (68%) underwent an oral radioactive calcium assay (45Ca). The impact of dietary and supplemental calcium on intestinal fractional calcium absorption was evaluated, and factors independently associated with nephrolithiasis were determined.<br><br>RESULTS: Fractional calcium absorption decreased with increased calcium intake, with no difference between dietary and supplemental calcium. Fractional calcium absorption was higher in women with a nephrolithiasis history among all calcium intake groups. Increased dietary calcium intake reduced the likelihood of nephrolithiasis by 45% to 54% (p=0.03). Women with a history of nephrolithiasis were less likely to supplement calcium (p<0.001). In adjusted analyses women who supplemented calcium were 21% to 38% less likely to have a nephrolithiasis history (p=0.007) and there was a 24% increased risk of kidney stones for each 10% increase in fractional calcium absorption (p=0.008).<br><br>CONCLUSIONS: Fractional calcium absorption is higher in women with a history of nephrolithiasis. Higher intestinal fractional calcium absorption is associated with a greater risk of historical nephrolithiasis. Dietary and supplemental calcium decrease fractional calcium absorption, and may protect against nephrolithiasis.}, }
@article {pmid22321032, year = {2012}, author = {Gadge, NB and Jalalpure, SS}, title = {Curative treatment with extracts of Bombax ceiba fruit reduces risk of calcium oxalate urolithiasis in rats.}, journal = {Pharmaceutical biology}, volume = {50}, number = {3}, pages = {310-317}, doi = {10.3109/13880209.2011.604332}, pmid = {22321032}, issn = {1744-5116}, mesh = {Animals ; Bombax/*chemistry ; Calcium/metabolism ; Calcium Oxalate/*metabolism ; Disease Models, Animal ; Ethylene Glycol/toxicity ; Female ; Fruit ; Hyperoxaluria/complications ; Male ; Medicine, Traditional ; Phosphates/metabolism ; Plant Extracts/*pharmacology ; Rats ; Rats, Wistar ; Urolithiasis/*drug therapy/etiology/pathology ; }, abstract = {CONTEXT: Drawbacks of presently available treatments for urolithiasis necessitate finding the treatment of hyperoxaluria specifically aimed at reduction in oxalate excretion. Interestingly, many Indian tribes use Bombax ceiba L. (Bombacaceae) fruits as a traditional medicine for the treatment of urinary stones.<br><br>OBJECTIVE: The present study investigated the efficacy of B. ceiba fruit extracts as curative agents in experimentally induced calcium oxalate urolithiatic rats.<br><br>MATERIALS AND METHODS: Calcium oxalate lithiasis was induced in rats by oral administration of 0.75% ethylene glycol for 14 consecutive days. Treatments with aqueous and ethanol extract of B. ceiba fruit (400&#x2009;mg/kg body weight) was performed in the same manner for further 14 consecutive days. Cystone (750&#x2009;mg/kg body weight) was used as reference antiurolithiatic drug. The urinary excretion and kidney deposition of offending salt components, and serum biochemical parameters were investigated.<br><br>RESULTS: Oral administration of ethylene glycol resulted in hyperoxaluria and increased renal excretion of calcium and phosphate. However, supplementation with aqueous and ethanol extracts of B. ceiba fruit significantly (p&#x2009;<&#x2009;0.05) reduced the elevated urinary oxalate, showing a regulatory action on endogenous oxalate synthesis. The increased deposition of stone forming constituents in kidneys of calculogenic rats was also significantly lowered with curative treatment of aqueous and ethanol extract.<br><br>DISCUSSION AND CONCLUSION: The results indicate that the fruit of B. ceiba is endowed with lithontriptic activity warranting further development for curative treatment of urolithiasis.}, }
@article {pmid22295079, year = {2012}, author = {Jgamadze, D and Bergen, J and Stone, D and Jang, JH and Schaffer, DV and Isacoff, EY and Pautot, S}, title = {Colloids as mobile substrates for the implantation and integration of differentiated neurons into the mammalian brain.}, journal = {PloS one}, volume = {7}, number = {1}, pages = {e30293}, pmid = {22295079}, issn = {1932-6203}, support = {PN2 EY1018241/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Brain/*cytology ; Calcium/metabolism ; *Cell Differentiation ; Cell Survival ; Cell Transplantation/*methods ; Colloids ; Hippocampus/cytology/metabolism ; Induced Pluripotent Stem Cells/cytology ; Injections ; Ion Channels/genetics ; Luminescent Proteins/genetics ; Male ; Molecular Imaging ; *Motion ; Neural Stem Cells/cytology ; Neurons/*cytology/metabolism/*transplantation ; Rats ; Time Factors ; Transduction, Genetic ; }, abstract = {Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and there have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is that differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture growth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these problems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even transfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The transplanted cells have a 76% cell survival rate one week post-surgery. At this time, most transplanted neurons have left their beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute uniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the transplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation, calcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host neurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell survival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach, which could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising prospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons.}, }
@article {pmid22285391, year = {2012}, author = {Niimi, K and Yasui, T and Hirose, M and Hamamoto, S and Itoh, Y and Okada, A and Kubota, Y and Kojima, Y and Tozawa, K and Sasaki, S and Hayashi, Y and Kohri, K}, title = {Mitochondrial permeability transition pore opening induces the initial process of renal calcium crystallization.}, journal = {Free radical biology &amp; medicine}, volume = {52}, number = {7}, pages = {1207-1217}, doi = {10.1016/j.freeradbiomed.2012.01.005}, pmid = {22285391}, issn = {1873-4596}, mesh = {Animals ; Blotting, Western ; Calcium/*chemistry/*metabolism ; Calcium Oxalate/*metabolism ; Cells, Cultured ; Crystallization ; Cyclosporine/pharmacology ; Immunoenzyme Techniques ; Immunosuppressive Agents/pharmacology ; Kidney/*metabolism/*pathology ; Male ; Membrane Potential, Mitochondrial/drug effects ; Mitochondrial Membrane Transport Proteins/*metabolism ; Mitochondrial Permeability Transition Pore ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Renal tubular cell injury induced by oxidative stress via mitochondrial collapse is thought to be the initial process of renal calcium crystallization. Mitochondrial collapse is generally caused by mitochondrial permeability transition pore (mPTP) opening, which can be blocked by cyclosporine A (CsA). Definitive evidence for the involvement of mPTP opening in the initial process of renal calcium crystallization, however, is lacking. In this study, we examined the physiological role of mPTP opening in renal calcium crystallization in vitro and in vivo. In the in vitro study, cultured renal tubular cells were exposed to calcium oxalate monohydrate (COM) crystals and treated with CsA (2 μM). COM crystals induced depolarization of the mitochondrial membrane potential and generated oxidative stress as evaluated by Cu-Zn SOD and 4-HNE. Furthermore, the expression of cytochrome c and cleaved caspase 3 was increased and these effects were prevented by CsA. In the in vivo study, Sprague-Dawley rats were administered 1% ethylene glycol (EG) to generate a rat kidney stone model and then treated with CsA (2.5, 5.0, and 10.0 mg/kg/day) for 14 days. EG administration induced renal calcium crystallization, which was prevented by CsA. Mitochondrial collapse was demonstrated by transmission electron microscopy, and oxidative stress was evaluated by measuring Cu-Zn SOD, MDA, and 8-OHdG generated by EG administration, all of which were prevented by CsA. Collectively, our results provide compelling evidence for a role of mPTP opening and its associated mitochondrial collapse, oxidative stress, and activation of the apoptotic pathway in the initial process of renal calcium crystallization.}, }
@article {pmid22207105, year = {2012}, author = {Yang, L and Chen, JH and Cai, D and Wang, LY and Zha, XL}, title = {Osteopontin and integrin are involved in cholesterol gallstone formation.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {18}, number = {1}, pages = {BR16-23}, pmid = {22207105}, issn = {1643-3750}, mesh = {Animals ; Bile/*metabolism ; Blotting, Western ; Calcium/metabolism ; *Diet ; Female ; Gallbladder/metabolism ; Gallstones/*metabolism/pathology ; Guinea Pigs ; Humans ; Immunohistochemistry ; Integrin alphaV/*metabolism ; Liver/metabolism ; Male ; Osteopontin/blood/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {BACKGROUND: This study aimed to investigate the role of osteopontin and its receptor, integrin αv, in gallstone formation using human tissue specimens and a guinea pig lithogenic model.<br><br>MATERIAL/METHODS: The nucleation role of osteopontin was determined in patients' and normal gallbladder bile samples in vitro. Normal gallbladder was the control, and gallstone gallbladders were divided into group I (with normal epithelia) and group II (with degenerated epithelia) based on pathology change. Immunostaining, mRNA and protein expressions of osteopontin and integrin &#x3b1;v were analyzed. The animals were randomly divided into a lithogenic diet group and a normal diet group; the osteopontin mRNA expression in gallbladder and liver and osteopontin concentrations were determined.<br><br>RESULTS: Osteopontin prolonged nucleation time and inhibited the pro-nucleating role induced by calcium in human bile in vitro. Immunostaining for osteopontin and integrin &#x3b1;v in human gallbladder tissues showed a higher reactivity in Group I than control group and Group II. The immunostaining in Group II was weaker than control group; similar results were observed for mRNA and protein expression of osteopontin and integrin &#x3b1;v. In the animal assay, the mRNA expression and concentration of osteopontin in gallbladder and liver gradually increased at initial stages and decreased in later stages. The concentrations of osteopontin in bile and serum of guinea pig showed similar trends.<br><br>CONCLUSIONS: Our results suggest that osteopontin is involved in cholesterol gallstone formation, and the role of osteopontin might correlate with integrin &#x3b1;v and calcium.}, }
@article {pmid22178870, year = {2011}, author = {Fatima, A and Xu, G and Shao, K and Papadopoulos, S and Lehmann, M and Arnáiz-Cot, JJ and Rosa, AO and Nguemo, F and Matzkies, M and Dittmann, S and Stone, SL and Linke, M and Zechner, U and Beyer, V and Hennies, HC and Rosenkranz, S and Klauke, B and Parwani, AS and Haverkamp, W and Pfitzer, G and Farr, M and Cleemann, L and Morad, M and Milting, H and Hescheler, J and Saric, T}, title = {In vitro modeling of ryanodine receptor 2 dysfunction using human induced pluripotent stem cells.}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology}, volume = {28}, number = {4}, pages = {579-592}, pmid = {22178870}, issn = {1421-9778}, support = {R01 HL016152/HL/NHLBI NIH HHS/United States ; HL 16152/HL/NHLBI NIH HHS/United States ; }, mesh = {Action Potentials ; Calcium/metabolism ; Catecholamines/metabolism ; Cell Differentiation ; Colforsin/metabolism ; Cyclic AMP/metabolism ; Electrocardiography ; Heterozygote ; Humans ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Karyotyping ; *Models, Biological ; Mutation ; Myocytes, Cardiac/cytology/metabolism ; Patch-Clamp Techniques ; Phenotype ; Ryanodine Receptor Calcium Release Channel/genetics/*metabolism ; Tachycardia, Ventricular/metabolism/pathology ; }, abstract = {BACKGROUND/AIMS: Induced pluripotent stem (iPS) cells generated from accessible adult cells of patients with genetic diseases open unprecedented opportunities for exploring the pathophysiology of human diseases in vitro. Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is an inherited cardiac disorder that is caused by mutations in the cardiac ryanodine receptor type 2 gene (RYR2) and is characterized by stress-induced ventricular arrhythmia that can lead to sudden cardiac death in young individuals. The aim of this study was to generate iPS cells from a patient with CPVT1 and determine whether iPS cell-derived cardiomyocytes carrying patient specific RYR2 mutation recapitulate the disease phenotype in vitro.<br><br>METHODS: iPS cells were derived from dermal fibroblasts of healthy donors and a patient with CPVT1 carrying the novel heterozygous autosomal dominant mutation p.F2483I in the RYR2. Functional properties of iPS cell derived-cardiomyocytes were analyzed by using whole-cell current and voltage clamp and calcium imaging techniques.<br><br>RESULTS: Patch-clamp recordings revealed arrhythmias and delayed afterdepolarizations (DADs) after catecholaminergic stimulation of CPVT1-iPS cell-derived cardiomyocytes. Calcium imaging studies showed that, compared to healthy cardiomyocytes, CPVT1-cardiomyocytes exhibit higher amplitudes and longer durations of spontaneous Ca(2+) release events at basal state. In addition, in CPVT1-cardiomyocytes the Ca(2+)-induced Ca(2+)-release events continued after repolarization and were abolished by increasing the cytosolic cAMP levels with forskolin.<br><br>CONCLUSION: This study demonstrates the suitability of iPS cells in modeling RYR2-related cardiac disorders in vitro and opens new opportunities for investigating the disease mechanism in vitro, developing new drugs, predicting their toxicity, and optimizing current treatment strategies.}, }
@article {pmid22138758, year = {2012}, author = {Theka, T and Rodgers, A and Lewandowski, S and Webber, D and Allie-Hamdulay, S}, title = {Effects of vitamin E ingestion on plasma and urinary risk factors for calcium oxalate urolithiasis in two population groups having different stone-risk profiles: evidence of different physiological handling mechanisms.}, journal = {Urological research}, volume = {40}, number = {2}, pages = {113-120}, pmid = {22138758}, issn = {1434-0879}, mesh = {Administration, Oral ; Adolescent ; Adult ; *Black People ; Calcium Oxalate/*metabolism ; Chylomicrons/metabolism ; Citrates/metabolism ; Dietary Supplements ; Humans ; Male ; Risk Factors ; South Africa ; Thiobarbituric Acid Reactive Substances/metabolism ; Urolithiasis/*epidemiology/*ethnology/metabolism ; Vitamin E/administration &amp; dosage/blood/*pharmacology ; *White People ; Young Adult ; alpha-Tocopherol/metabolism ; }, abstract = {It has been demonstrated that vitamin E supplementation reduces calciuria and oxaluria and that it may also prevent oxalate-mediated peroxidative injury, all of which reduce the risk of calcium oxalate urolithiasis. In view of the significant difference in stone occurrence in black (B) and white (W) South Africans, we undertook to investigate the effects of vitamin E supplementation in subjects from these two groups. Five healthy males from each group ingested one capsule (400 IU) of vitamin E daily for 60 days. Blood and 24 h urine samples were collected at baseline and on day 60; 24 h dietary questionnaires were simultaneously completed. Urine composition was determined by routine analyses. Urinary and plasma TBARS were determined using a commercially available assay kit while plasma vitamin E was determined by reverse phase HPLC. Plasma vitamin E increased significantly in W but not in B. Urinary and plasma TBARS did not increase in either group. Urinary citrate increased significantly in both groups but the percentage increase in W (169%) was greater than that in B (82%). No other urinary parameter changed significantly. The increase in plasma vitamin E in W but not in B suggests either that the mechanism by which it is packaged into chylomicrons, which are secreted into the systemic circulation, is suppressed in the latter group or that it is differentially absorbed in the two groups. Similarly, to explain the greater increase in citraturia in W compared to B, we speculate that inhibition of lipogenesis of arachidonic acid by vitamin E, ultimately leading to an increase in citraturia, occurs to a lesser extent in B than in W.}, }
@article {pmid22137721, year = {2011}, author = {Xi, QL and Wang, SG and Ye, ZQ and Zhu, ZW and Li, C and Bai, J and Yu, X and Liu, JH}, title = {Effect of silencing VDR gene in kidney on renal epithelial calcium transporter proteins and urinary calcium excretion in genetic hypercalciuric stone-forming rats.}, journal = {Urology}, volume = {78}, number = {6}, pages = {1442.e1-7}, doi = {10.1016/j.urology.2011.08.051}, pmid = {22137721}, issn = {1527-9995}, mesh = {Analysis of Variance ; Animals ; Calbindins ; Calcitriol/blood ; Calcium/*metabolism ; Calcium Channels/metabolism ; Calcium-Transporting ATPases/metabolism ; Epithelium/metabolism ; Gene Expression Regulation ; Gene Silencing ; Hypercalciuria/genetics ; Kidney/enzymology/*metabolism ; Male ; Models, Animal ; Parathyroid Hormone/blood ; Phosphorus/blood ; RNA, Messenger/*metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Calcitriol/*genetics/*metabolism ; Receptors, Calcium-Sensing/*metabolism ; S100 Calcium Binding Protein G/metabolism ; Sodium-Calcium Exchanger/metabolism ; TRPV Cation Channels/metabolism ; }, abstract = {OBJECTIVE: To address the molecular mechanisms that the vitamin D receptor (VDR) in the kidney might contribute to decreased renal calcium reabsorption in idiopathic hypercalciuria using genetic hypercalciuric stone-forming (GHS) rats.<br><br>METHODS: We silenced the VDR gene in the GHS and normal control (NC) rat kidney in vivo using adenovirus vector-delivered microRNA targeting VDR through renal venous transduction. On days 3-21 after injection with adenovirus, the expression levels of the VDR, calcium-sensing receptor, and epithelial calcium transporters in the kidney were detected. The urine calcium and serum calcium, phosphorus, 1,25(OH)(2)D(3), and parathyroid hormone levels were measured.<br><br>RESULTS: The basal expression levels in the kidney tissues of VDR, calbindin-D(28k), and calcium-sensing receptor were significantly greater in the GHS rats than in the NC rats, and the basal expression levels of transient receptor potential vanilloid receptor subtype 5, transient receptor potential vanilloid receptor subtype 6, calbindin-D(9k), and plasma membrane calcium-adenosine triphosphatase were significantly lower in the GHS rats than in the NC rats. VDR knockdown in the kidney caused significant increase in renal transient receptor potential vanilloid receptor subtype 5, sodium/calcium exchanger, and calbindin-D(9k) expression levels in the GHS rats. The GHS rats excreted significantly more urine calcium after VDR knockdown. The serum calcium, phosphorus, parathyroid hormone, and 1,25(OH)(2)D(3) levels were not altered during the study period in the GHS and NC rats.<br><br>CONCLUSION: Our findings suggest that VDR knockdown in the kidney can upregulate the expression of transient receptor potential vanilloid receptor subtype 5 in GHS rats. However, VDR depletion results in an increase in urine calcium excretion. The role of VDR in the hypercalciuric formation needs to be elucidated further.}, }
@article {pmid22127335, year = {2012}, author = {Calvez, J and Poupin, N and Chesneau, C and Lassale, C and Tomé, D}, title = {Protein intake, calcium balance and health consequences.}, journal = {European journal of clinical nutrition}, volume = {66}, number = {3}, pages = {281-295}, doi = {10.1038/ejcn.2011.196}, pmid = {22127335}, issn = {1476-5640}, mesh = {Absorption ; Animals ; Bone Density/drug effects ; Bone Diseases/*etiology ; Bone and Bones/*drug effects ; Calcium/*metabolism ; *Diet ; Dietary Proteins/administration &amp; dosage/*pharmacology ; Fractures, Bone/etiology ; Humans ; Intestinal Mucosa/metabolism ; Kidney/*drug effects ; Kidney Diseases/*etiology ; }, abstract = {High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet.}, }
@article {pmid22116536, year = {2012}, author = {Wang, S and Wang, X and Wu, J and Lin, Y and Chen, H and Zheng, X and Zhou, C and Xie, L}, title = {Association of vitamin D receptor gene polymorphism and calcium urolithiasis in the Chinese Han population.}, journal = {Urological research}, volume = {40}, number = {4}, pages = {277-284}, pmid = {22116536}, issn = {1434-0879}, mesh = {Adult ; Aged ; Aged, 80 and over ; Asian People/*genetics ; Calcium/*metabolism ; Female ; Haplotypes ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Receptors, Calcitriol/*genetics ; Urolithiasis/*genetics ; }, abstract = {To investigate the effect of the vitamin D receptor (VDR) Fok I Bsm I Dde I Apa I Taq I polymorphism on the clinical presentation of calcium urolithiasis, 464 patients with urolithiasis and 450 age- and sex-matched healthy controls were recruited from The First Affiliated Hospital of Zhejiang University between January 2010 and March 2011. Five SNPs of VDR polymorphism were detected using polymerase chain reaction-based restriction analysis. The frequency of VDR Apa I genotypes between the patients and the healthy controls was significantly different (P = 0.006). Apa I a allele was found to be associated with increased risk of stone recurrence (P = 0.028). We also found Fok I Dde I Apa I showed a significant difference between male and female in the patients group (P < 0.05). Haplotype analysis of the five VDR polymorphisms showed a significant association with urolithiasis (global-P value = 0.0001). Genetic polymorphisms of VDR are important in the clinical presentation of patients with calcium urolithiasis in the Han population of southern China.}, }
@article {pmid21960240, year = {2011}, author = {Nagata, M and Takayama, T and Mugiya, S and Ohzono, S}, title = {[Pharmacotherapy for preventing calcium containing stone formation].}, journal = {Clinical calcium}, volume = {21}, number = {10}, pages = {1530-1534}, pmid = {21960240}, issn = {0917-5857}, mesh = {Allopurinol/*pharmacology/*therapeutic use ; Animals ; Calcium/*metabolism ; Citrates/pharmacology/therapeutic use ; Drugs, Chinese Herbal/pharmacology/therapeutic use ; Humans ; Magnesium Compounds/pharmacology/therapeutic use ; Phytotherapy ; Plant Extracts/pharmacology/therapeutic use ; Secondary Prevention ; Sodium Chloride Symporter Inhibitors/pharmacology/therapeutic use ; Urinary Calculi/*drug therapy/metabolism/*prevention &amp; control ; Vitamin B 6/pharmacology/therapeutic use ; Xanthine Oxidase/antagonists &amp; inhibitors ; }, abstract = {Many urinary tract stones consist of calcium, and has high relapse rate. Accordingly, it is very important to prevent calcium-containing stone formation. This paper describes about effects and mechanisms for Xanthine oxidase inhibitor, citrate formulation, magnesium formulation, thiazides, vitamin B(6), extract of Quercus salicina Blume and chorei-to (medical herb) . Recent new drugs and the elucidation of new metabolic pathways may lead to the development of prevention of urolithiasis.}, }
@article {pmid21960239, year = {2011}, author = {Moriyama, MT}, title = {[Diet therapy and life guidance to prevent calcium stones].}, journal = {Clinical calcium}, volume = {21}, number = {10}, pages = {1522-1529}, pmid = {21960239}, issn = {0917-5857}, mesh = {Calcium/*metabolism ; Dyslipidemias/complications ; Energy Intake ; Feeding Behavior ; Humans ; Hyperglycemia/complications ; Hypertension/complications ; *Life Style ; Obesity/complications ; Secondary Prevention ; Urinary Calculi/*diet therapy/etiology/metabolism/*prevention &amp; control ; }, abstract = {Urolithiasis patients have a low continuation rate with regard to visiting the hospital and undergoing periodic check-ups following therapy. The increased Westernization of diets has played a major role in its onset, and it is believed to be a lifestyle disease. Therefore, the prevention of relapse is difficult without improving the patients' lifestyle and eating habits, and it has been defined as a disease with an extremely high relapse rate. On the other hand, it is believed that the opportunity for periodic visits to the hospital and check-ups can be assured by continuously performing careful dietary interventions appropriate for each patient and by educating patients about the disease, thereby contributing to the prevention of relapses of urolithiasis.}, }
@article {pmid21960233, year = {2011}, author = {Hamamoto, S and Taguchi, K and Fujii, Y}, title = {[Molecular mechanism of renal stone formation].}, journal = {Clinical calcium}, volume = {21}, number = {10}, pages = {1481-1487}, pmid = {21960233}, issn = {0917-5857}, mesh = {Agglutination ; Animals ; Calcium/metabolism ; Calcium Oxalate/metabolism ; Cell Adhesion ; Crystallization ; Glycoproteins/physiology ; Humans ; Kidney Calculi/chemistry/*genetics/*metabolism ; Kidney Tubules/cytology/injuries/metabolism ; Macrophages/physiology ; Oxalates/metabolism ; }, abstract = {Urolithiasis is a multifactorial disease involving environmental and gentic factors. Calcium-containing stones, which are>90% of all stones, detected most frequently ; however, radically effective prevention and detailed investigation of crystal formation have not been established. Renal stone formation is a complex multistep process that includes supersaturation, crystal nucleation, growth, and aggregation. In the early stage of crystal formation, exposure to high concentrations of oxalate can induce renal tubular cell injury, following crystal attachment to renal tubular cell in which stone matrix proteins or urinary high molecular substances play an important role as a promoter or inhibitor respectively. Recent study speculated that renal macrophage could englobe crystals and might digest them. In this part, we propose the molecular mechanism that has been newly investigated recently, in renal stone formation.}, }
@article {pmid21960231, year = {2011}, author = {Aruga, S and Honma, Y}, title = {[Renal calcium excretion and urolithiasis].}, journal = {Clinical calcium}, volume = {21}, number = {10}, pages = {1465-1472}, pmid = {21960231}, issn = {0917-5857}, mesh = {Adenylyl Cyclases/genetics ; Bone Resorption/etiology ; Calcium/*metabolism ; Citric Acid/metabolism ; Dietary Proteins/adverse effects ; Humans ; Hypercalciuria/*complications/drug therapy/genetics ; Kidney/*metabolism ; Kidney Calculi/*etiology/metabolism ; Oxalates/metabolism ; Phosphates/metabolism ; Receptors, Calcium-Sensing/genetics ; Risk Factors ; Sodium Chloride, Dietary/adverse effects ; Uric Acid/metabolism ; }, abstract = {Patients with urolithiasis have been increasing in the world, especially morbidity of calcium nephrolithiasis has been increasing in the advanced countries. The changes in the environmental factors including alternation of diet are said to be associated with the increment of morbidity of kidney stone. Idiopathic hypercalciuria is one of the most important risk factor of calcium nephrolithiasis and is classified into absorptive, resorptive, and renal leak. Though the origins of these three types of hypercalciuria are different, increased bone resorption and increased calcium absorption from gut tend to be observed simultaneously. Not only genetic abnormalities in the proteins which are involved in calcium metabolisms but environmental factors such as high sodium intake and chronic acid load caused by increased ingestion of animal protein have been considered to be associated with increased urinary calcium excretion. Renal metabolisms of oxalate and phosphate which are important compositions of calcium containing stone, uric acid as a promoter and citrate as a inhibitor of nephrolithiasis are also described.}, }
@article {pmid21960230, year = {2011}, author = {Kohjimoto, Y and Sasaki, Y and Hara, I}, title = {[Clinical strategies for prevention of drug-induced urinary calculi].}, journal = {Clinical calcium}, volume = {21}, number = {10}, pages = {1457-1463}, pmid = {21960230}, issn = {0917-5857}, mesh = {Allopurinol/adverse effects ; Anti-Bacterial Agents/*adverse effects ; Ascorbic Acid/adverse effects ; Benzbromarone/adverse effects ; Calcium/metabolism ; Calcium Compounds/adverse effects ; Carbonic Anhydrase Inhibitors/adverse effects ; Crystallization ; Diuretics/*adverse effects ; Drug Combinations ; Furosemide/adverse effects ; Glucocorticoids/adverse effects ; Humans ; Magnesium Silicates/adverse effects ; Oxalates/metabolism ; Protease Inhibitors/*adverse effects ; Purines/metabolism ; Time Factors ; Triamterene/*adverse effects ; Urinary Calculi/*chemically induced/chemistry/*prevention &amp; control ; Vitamin D/adverse effects ; }, abstract = {Drug-induced urinary calculi, although they account for only 1-2% of urinary calculi, deserve consideration because most of them are preventable. In the drug-containing calculi resulting from the crystallization of a certain drug and its metabolites in the urine, stone analysis can identify the responsible drug. While, in the drug-induced metabolic calculi caused by interference with calcium, oxalate and purine metabolism, careful clinical inquiry is necessary to reveal involvement of a certain drug in stone formation. Better awareness of the possible drugs with lithogenic potential and close surveillance of patients on long-term treatment with these drugs are necessary. Especially, in patients with a history of urolithiaisis, prescription of lithogenic drugs deserve careful consideration.}, }
@article {pmid21960228, year = {2011}, author = {Okuyama, M}, title = {[Epidemiology of urolithiasis].}, journal = {Clinical calcium}, volume = {21}, number = {10}, pages = {1442-1447}, pmid = {21960228}, issn = {0917-5857}, mesh = {Body Mass Index ; Calcium/metabolism ; Calcium, Dietary/administration &amp; dosage ; Dietary Fats/adverse effects ; Dietary Proteins/adverse effects ; Eating/physiology ; Feeding Behavior ; Female ; Global Health ; Humans ; Incidence ; Japan/epidemiology ; Male ; Prevalence ; Time Factors ; Urolithiasis/*epidemiology/etiology ; Weight Gain ; }, abstract = {Recently, urolithiasis is increasing in the world. The onset of urolithiasis is considered to associate with high protein and fat dietary habits. In the articles, using epidemiological method and research, the prevalence and incidence of the upper urinary tract stones as kidney and ureter is described. In addition, the association between dietary intake and calcium metabolism is reviewed.}, }
@article {pmid21947122, year = {2011}, author = {Reilly, RF and Huang, CL}, title = {The mechanism of hypocalciuria with NaCl cotransporter inhibition.}, journal = {Nature reviews. Nephrology}, volume = {7}, number = {11}, pages = {669-674}, pmid = {21947122}, issn = {1759-507X}, mesh = {Animals ; Calcium/urine ; Calcium Metabolism Disorders/*chemically induced/urine ; Diet, Sodium-Restricted ; Disease Models, Animal ; Gitelman Syndrome/metabolism ; Humans ; Kidney Calculi/*drug therapy/*prevention &amp; control ; Kidney Tubules, Distal/drug effects/metabolism ; Kidney Tubules, Proximal/drug effects/metabolism ; Mice ; Mice, Knockout ; Sodium Chloride Symporter Inhibitors/administration &amp; dosage/*adverse effects ; Sodium-Potassium-Chloride Symporters/metabolism ; }, abstract = {Thiazide diuretics are used to prevent the recurrence of calcium-containing kidney stones. The ability of these drugs to reduce urinary calcium excretion has a key role in this process. Although studies have shown a reduction in the recurrence rate of calcium-containing stones in patients treated with thiazides, whether hypocalciuria results from increased calcium reabsorption in the proximal or distal nephron is still unclear. When extracellular fluid volume is considerably reduced, the proximal tubule is likely to have a major role in thiazide-induced hypocalciuria. This process frequently occurs when high doses of thiazides and sodium restriction are prescribed for the treatment of kidney stone disease. The distal tubule is predominantly involved in NaCl cotransporter inhibition-induced hypocalciuria when the extracellular fluid volume is not reduced, a clinical scenario observed in patients with Gitelman syndrome. In this Perspectives article, we discuss the evidence supporting the hypocalciuric effects of NaCl cotransporter inhibition in the proximal and distal nephron.}, }
@article {pmid21940456, year = {2011}, author = {Huang, YA and Stone, LM and Pereira, E and Yang, R and Kinnamon, JC and Dvoryanchikov, G and Chaudhari, N and Finger, TE and Kinnamon, SC and Roper, SD}, title = {Knocking out P2X receptors reduces transmitter secretion in taste buds.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {31}, number = {38}, pages = {13654-13661}, pmid = {21940456}, issn = {1529-2401}, support = {R56 DC006308/DC/NIDCD NIH HHS/United States ; R56 DC006308-06/DC/NIDCD NIH HHS/United States ; R01 DC007630/DC/NIDCD NIH HHS/United States ; R01 DC000374/DC/NIDCD NIH HHS/United States ; R01 DC000374-22/DC/NIDCD NIH HHS/United States ; R01 DC006308/DC/NIDCD NIH HHS/United States ; P30 DC004657/DC/NIDCD NIH HHS/United States ; R01 DC007630-05/DC/NIDCD NIH HHS/United States ; R01 DC007495/DC/NIDCD NIH HHS/United States ; P30DC004657/DC/NIDCD NIH HHS/United States ; 5R01DC000374/DC/NIDCD NIH HHS/United States ; P30 DC004657-01/DC/NIDCD NIH HHS/United States ; 2R01DC007630/DC/NIDCD NIH HHS/United States ; R01DC006308/DC/NIDCD NIH HHS/United States ; R01 DC007495-05/DC/NIDCD NIH HHS/United States ; R01DC007495/DC/NIDCD NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/*metabolism ; Animals ; Calcium/metabolism ; Connexins/metabolism ; Male ; Mice ; Mice, Inbred Strains ; Mice, Knockout ; Nerve Tissue Proteins/metabolism ; Potassium Chloride/pharmacology ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Purinergic P2X/*biosynthesis/genetics ; Receptors, Purinergic P2X2/*biosynthesis ; Synaptic Transmission/genetics/*physiology ; TRPM Cation Channels/metabolism ; Taste/physiology ; Taste Buds/drug effects/*metabolism/ultrastructure ; }, abstract = {In response to gustatory stimulation, taste bud cells release a transmitter, ATP, that activates P2X2 and P2X3 receptors on gustatory afferent fibers. Taste behavior and gustatory neural responses are largely abolished in mice lacking P2X2 and P2X3 receptors [P2X2 and P2X3 double knock-out (DKO) mice]. The assumption has been that eliminating P2X2 and P2X3 receptors only removes postsynaptic targets but that transmitter secretion in mice is normal. Using functional imaging, ATP biosensor cells, and a cell-free assay for ATP, we tested this assumption. Surprisingly, although gustatory stimulation mobilizes Ca(2+) in taste Receptor (Type II) cells from DKO mice, as from wild-type (WT) mice, taste cells from DKO mice fail to release ATP when stimulated with tastants. ATP release could be elicited by depolarizing DKO Receptor cells with KCl, suggesting that ATP-release machinery remains functional in DKO taste buds. To explore the difference in ATP release across genotypes, we used reverse transcriptase (RT)-PCR, immunostaining, and histochemistry for key proteins underlying ATP secretion and degradation: Pannexin1, TRPM5, and NTPDase2 (ecto-ATPase) are indistinguishable between WT and DKO mice. The ultrastructure of contacts between taste cells and nerve fibers is also normal in the DKO mice. Finally, quantitative RT-PCR show that P2X4 and P2X7, potential modulators of ATP secretion, are similarly expressed in taste buds in WT and DKO taste buds. Importantly, we find that P2X2 is expressed in WT taste buds and appears to function as an autocrine, positive feedback signal to amplify taste-evoked ATP secretion.}, }
@article {pmid21911305, year = {2012}, author = {Konstantynowicz, J and Porowski, T and Zoch-Zwierz, W and Wasilewska, J and Kadziela-Olech, H and Kulak, W and Owens, SC and Piotrowska-Jastrzebska, J and Kaczmarski, M}, title = {A potential pathogenic role of oxalate in autism.}, journal = {European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society}, volume = {16}, number = {5}, pages = {485-491}, doi = {10.1016/j.ejpn.2011.08.004}, pmid = {21911305}, issn = {1532-2130}, mesh = {Adolescent ; Autistic Disorder/blood/*metabolism/urine ; Calcium Oxalate/blood/*metabolism/urine ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Male ; Oxalic Acid/blood/*metabolism/urine ; }, abstract = {BACKGROUND: Although autistic spectrum disorders (ASD) are a strongly genetic condition certain metabolic disturbances may contribute to clinical features. Metabolism of oxalate in children with ASD has not yet been studied.<br><br>AIM: The objective was to determine oxalate levels in plasma and urine in autistic children in relation to other urinary parameters.<br><br>METHOD: In this cross-sectional study, plasma oxalate (using enzymatic method with oxalate oxidase) and spontaneous urinary calcium oxalate (CaOx) crystallization (based on the Bonn-Risk-Index, BRI) were determined in 36 children and adolescents with ASD (26 boys, 10 girls) aged 2-18 years and compared with 60 healthy non-autistic children matched by age, gender and anthropometric traits.<br><br>RESULTS: Children with ASD demonstrated 3-fold greater plasma oxalate levels [5.60 (5th-95th percentile: 3.47-7.51)] compared with reference [(1.84 (5th-95th percentile: 0.50-4.70) &#x3bc;mol/L (p&#xa0;<&#xa0;0.05)] and 2.5-fold greater urinary oxalate concentrations (p&#xa0;<&#xa0;0.05). No differences between the two groups were found in urinary pH, citraturia, calciuria or adjusted CaOx crystallization rates based on BRI. Despite significant hyperoxaluria no evidence of kidney stone disease or lithogenic risk was observed in these individuals.<br><br>CONCLUSIONS: Hyperoxalemia and hyperoxaluria may be involved in the pathogenesis of ASD in children. Whether this is a result of impaired renal excretion or an extensive intestinal absorption, or both, or whether Ox may cross the blood brain barrier and disturb CNS function in the autistic children remains unclear. This appears to be the first report of plasma and urinary oxalate in childhood autism.}, }
@article {pmid21908029, year = {2012}, author = {Arrabal-Polo, MA and Arrabal-Martin, M and de Haro-Muñoz, T and Poyatos-Andujar, A and Palæo-Yago, F and Zuluaga-Gomez, A}, title = {Biochemical determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis.}, journal = {Urology}, volume = {79}, number = {1}, pages = {48-54}, doi = {10.1016/j.urology.2011.07.1382}, pmid = {21908029}, issn = {1527-9995}, mesh = {Adult ; Age Distribution ; Biomarkers/metabolism ; Calcium/*metabolism ; Chi-Square Distribution ; Cross-Sectional Studies ; Female ; Humans ; Incidence ; Kidney Calculi/chemistry/metabolism ; Male ; Middle Aged ; Nephrolithiasis/*diagnosis/*epidemiology ; Osteocalcin/metabolism ; Parathyroid Hormone/metabolism ; Phosphorus/*metabolism ; Prognosis ; Recurrence ; Risk Assessment ; Severity of Illness Index ; Sex Distribution ; Spain ; }, abstract = {OBJECTIVE: To analyze the biochemical alterations in plasma and the urine determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis.<br><br>METHODS: We performed a cross-sectional study of 120 patients divided into 2 groups: group 1, 60 patients without nephrolithiasis; and group 2, 60 patients with severe and/or recurrent calcium nephrolithiasis. In all patients, a study of renal function, calcium metabolism, and bone remodeling markers, and a study of the lithogenic factors were performed in urine after fasting and in 24-hour urine samples.<br><br>RESULTS: We observed greater values for phosphorus in group 1 than in group 2 (P=.03). Also, we found greater values for intact parathyroid hormone (P=.01), osteocalcin (P=.000), and &#x3b2;-crosslaps (P=.000) in group 2 than in group 1. In the 24-hour urine samples, significant differences were found between groups 1 and 2 in calciuria (11.7 vs 17.4 mg/dL; P=.000), citraturia (50.6 vs 33.5 mg/dL; P=.002), calcium/creatinine quotient (0.14 vs 0.20; P=.001), calcium/citrate quotient (0.05 vs 0.13; P=.04), and calcium/creatinine quotient after fasting (0.09 vs 0.16; P=.000).<br><br>CONCLUSION: We consider the determinants of severe and/or recurrent calcium lithiasis to be hypercalciuria and hypocitraturia and a calcium/citrate quotient>0.06. As risk markers we can consider phosphatemia<2.9 mg/dL, phosphate/chlorine quotient>35, alkaline phosphatase>80 U/L, intact parathyroid hormone>60 pg/mL, osteocalcin>16 ng/mL, &#x3b2;-crosslaps>0.400 ng/mL, and &#x3b2;-crosslaps/osteocalcin quotient>0.028.}, }
@article {pmid21856593, year = {2011}, author = {Miller, PD}, title = {Vitamin D, calcium, and cardiovascular mortality: a perspective from a plenary lecture given at the annual meeting of the American Association of Clinical Endocrinologists.}, journal = {Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists}, volume = {17}, number = {5}, pages = {798-806}, doi = {10.4158/EP11203.RA}, pmid = {21856593}, issn = {1934-2403}, mesh = {Calcium/*metabolism ; Cardiovascular Diseases/*metabolism/*mortality ; Congresses as Topic ; Humans ; Vitamin D/*metabolism ; }, abstract = {OBJECTIVE: To examine data showing associations between serum 25-hydroxyvitamin D levels and calcium intake and cardiovascular mortality.<br><br>METHODS: The articles reviewed include those published from 1992-2011 derived from search engines (PubMed, Scopus, Medscape) using the following search terms: vitamin D, calcium, cardiovascular events, cardiovascular mortality, all-cause mortality, vascular calcification, chronic kidney disease, renal stones, and hypercalciuria. Because these articles were not weighted (graded) on the level of evidence, this review reflects my own perspective on the data and how they should be applied to clinical management.<br><br>RESULTS: For skeletal health, vitamin D and calcium are both needed to ensure proper skeletal growth (modeling) and repair (remodeling). Nutritional deficiencies of either vitamin D or calcium may lead to a spectrum of metabolic bone disorders. Excessive consumption of either nutrient has been linked to a variety of medical disorders, such as hypercalcemia or renal stones. There have also been associations between vitamin D or calcium intake and cardiovascular disease. However, neither of these associations have established evidence nor known causality for increasing cardiovascular risk or all-cause mortality in patients with creatinine clearances greater than 60 mL/min. In patients with more severe chronic kidney disease, stronger data link excess calcium (or phosphorus) intake and increase in vascular calcification, but not mortality. The safe upper limit for vitamin D intake is at least 4000 IU daily and probably 10 000 IU daily; for calcium, the safe upper limit is between 2000 and 3000 mg daily.<br><br>CONCLUSIONS: While no solid scientific evidence validates that serum vitamin D levels between 15 and 70 ng/mL are associated with increased cardiovascular disease risk, stronger but inconsistent evidence shows an association between calcium supplementation greater than 500 mg daily and an increase in cardiovascular disease risk. Most professional societies suggest that replacement levels of these nutrients be personalized with the goal of reaching a 25-hydroxyvitamin D concentration between 30 and 50 ng/mL and a calcium intake of 1200 mg daily.}, }
@article {pmid21784822, year = {2011}, author = {Renkema, KY and Bindels, RJ and Hoenderop, JG}, title = {Role of the calcium-sensing receptor in reducing the risk for calcium stones.}, journal = {Clinical journal of the American Society of Nephrology : CJASN}, volume = {6}, number = {8}, pages = {2076-2082}, doi = {10.2215/CJN.00480111}, pmid = {21784822}, issn = {1555-905X}, mesh = {Adaptation, Physiological ; Animals ; Calcium/*metabolism/urine ; Calcium Channels/deficiency/genetics ; Crystallization ; Disease Models, Animal ; Homeostasis ; Humans ; Hypercalciuria/genetics/metabolism ; Kidney/*metabolism ; Mice ; Mice, Knockout ; Nephrolithiasis/etiology/genetics/metabolism/*prevention &amp; control ; Receptors, Calcium-Sensing/*metabolism ; TRPV Cation Channels/deficiency/genetics ; }, abstract = {The tight control of blood Ca2+ levels within a narrow range is essential for the performance of vital physiologic functions. Muscle contraction, neuronal excitation, and intracellular signaling processes acquisitively require Ca2+. It is the concerted action of intestine, bone, and kidney that controls the Ca2+ balance through the regulation of intestinal absorption, bone (de)mineralization, and renal excretion of Ca2+, respectively. Along the nephron, fine-tuning of blood Ca2+ levels takes place by Ca2+ reabsorption. The calciotropic hormones regulate Ca2+ transport processes, leading to whole-body Ca2+ homeostasis and, importantly, preserving a constant Ca2+ concentration in the blood. Defects in renal Ca2+ handling can lead to hypercalciuria, consecutive kidney stone formation, and obstructive nephropathy. Here we give an overview of the key players involved in normal Ca2+ management and describe the in-depth investigations on a renal hypercalciuric model of disease, the Trpv5 knockout mouse, which naturally displays molecular adaptations that prevent Ca2+ precipitation in the kidney.}, }
@article {pmid21707782, year = {2012}, author = {Clauss, M and Burger, B and Liesegang, A and Del Chicca, F and Kaufmann-Bart, M and Riond, B and Hässig, M and Hatt, JM}, title = {Influence of diet on calcium metabolism, tissue calcification and urinary sludge in rabbits (Oryctolagus cuniculus).}, journal = {Journal of animal physiology and animal nutrition}, volume = {96}, number = {5}, pages = {798-807}, doi = {10.1111/j.1439-0396.2011.01185.x}, pmid = {21707782}, issn = {1439-0396}, mesh = {Animal Feed/*analysis ; Animal Nutritional Physiological Phenomena ; Animals ; Calcinosis/*veterinary ; Calcium/*metabolism/urine ; Diet/*veterinary ; Feces/chemistry ; Female ; Male ; Rabbits/blood/*physiology/*urine ; Urinary Bladder ; }, abstract = {Rabbits absorb more calcium (Ca) from their diet than they require, and excrete surplus via urine, which therefore contains a typical 'sludge'. This makes rabbits susceptible to Ca-containing uroliths. But given the Ca content of diets of free-ranging specimens, and the limited reports of urinary sludge and Ca contents in free-ranging lagomorphs, we can suspect that rabbits are naturally adapted to high urinary Ca loads. We fed four groups of New Zealand hybrid rabbits [n = 28, age at start 5-6 weeks) pelleted diets consisting of lucerne hay only (L, Ca 2.32% dry matter (DM)], lucerne:oats 1:1 (LG, Ca 1.36%), grass hay only (G, Ca 1.04%), or grass:oats 1:1 (GG, 0.83%) for 25 weeks, with water available ad libitum. Diets were not supplemented with Ca, phosphorus, or vitamin D. Rabbits on diets LG and GG had lower food and water intakes, lower faeces and urine output, grew faster and had higher body mass at slaughter (mainly attributable to adipose tissue). Apparent Ca digestibility decreased in the order L-LG-G/GG. Rabbits on L had larger and heavier kidneys, more urinary sediment at sonography, and a higher urinary Ca content than the other groups. No animal showed signs of urolithiasis/calcinosis at X-ray, sonography, or gross pathology. Kidney/aorta histology only sporadically indicated Ca deposits, with no systematic difference between groups. Under the conditions of the experiment, dietary Ca loads in legume hay do not appear problematic for rabbits, and other factors, such as water supply and level of activity may be important contributors to urolithiasis development in veterinary patients. However, due to the lower Ca content of grass hay, the significantly lower degree of urinary sludge formation, and the significantly higher water intake related with grass hay feeding, grass hay-dominated diets are to be recommended for rabbits in which urolithiasis prevention is an issue.}, }
@article {pmid21652546, year = {2012}, author = {Esposito, T and Rendina, D and Aloia, A and Formicola, D and Magliocca, S and De Filippo, G and Muscariello, R and Mossetti, G and Gianfrancesco, F and Strazzullo, P}, title = {The melatonin receptor 1A (MTNR1A) gene is associated with recurrent and idiopathic calcium nephrolithiasis.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {27}, number = {1}, pages = {210-218}, doi = {10.1093/ndt/gfr216}, pmid = {21652546}, issn = {1460-2385}, mesh = {Adult ; Base Sequence ; Biomarkers/*metabolism ; Calcium/*metabolism ; Case-Control Studies ; DNA/genetics ; DNA Mutational Analysis ; Electrophoretic Mobility Shift Assay ; Female ; Humans ; Kidney Calculi/*genetics/pathology ; Male ; Middle Aged ; Nephrolithiasis/*genetics/pathology ; Polymorphism, Single Nucleotide/*genetics ; Prognosis ; Real-Time Polymerase Chain Reaction ; Receptor, Melatonin, MT1/*genetics ; *Recurrence ; }, abstract = {BACKGROUND: Experimental evidence indicate that melatonin regulates some renal tubular functions via specific melatonin receptors (MTNRs) located in the kidney of several avian and mammalian species, including humans. We hypothesized that single nucleotide polymorphisms (SNPs) in the melatonin receptor 1A gene (MTNR1A) might influence the risk of calcium nephrolithiasis.<br><br>METHODS: We performed a systematic analysis of the MTNR1A gene in 246 recurrent calcium stone formers (136 men, 110 women; mean age 40.2 &#xb1; 12.0 years; body mass index 25.8 &#xb1; 4.5 kg/m2) and 269 healthy controls comparable for age and gender without a history of nephrolithiasis.<br><br>RESULTS: Two SNPs in Intron 1 of MTNR1A were significantly associated with calcium nephrolithiasis: rs13140012 (P = 0.0004) and rs6553010 (P = 0.009). The haplotypes resulting from the two SNPs were also differently distributed between stone formers and controls, the haplotype A-T being more represented among stone formers (P = 0.00001) and the haplotype T-C being more common in healthy controls (P = 0.00001). Preliminary functional studies showed that the SNP rs13140012 could modify the binding sites for transcription factors.<br><br>CONCLUSION: The results of this case-control study indicate a strong association between allelic variants of MTNR1A and recurrent calcium nephrolithiasis.}, }
@article {pmid21629339, year = {2011}, author = {Felsenfeld, AJ and Levine, BS and Kleeman, CR}, title = {Fuller Albright and our current understanding of calcium and phosphorus regulation and primary hyperparathyroidism.}, journal = {Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia}, volume = {31}, number = {3}, pages = {346-357}, doi = {10.3265/Nefrologia.pre2011.Mar.10774}, pmid = {21629339}, issn = {1989-2284}, mesh = {Calcium/*metabolism ; History, 20th Century ; Humans ; Hyperparathyroidism, Primary/*metabolism ; Intestinal Absorption ; Phosphorus/*metabolism ; Renal Insufficiency/etiology ; }, abstract = {The major contributions of Fuller Albright to our understanding of calcium and phosphorus regulation and primary hyperparathyroidism are highlighted. Albright was the first investigator to initiate a systematic study of mineral metabolism. With resources limited to the measurement of serum calcium and phosphorus and the infusion of parathyroid extract, Albright used balance studies to establish a framework for our understanding of calcium and phosphorus regulation and primary hyperparathyroidism. Albright was the first to show that the etiology of primary hyperparathyroidism could be from either an adenoma or hyperplasia of the parathyroid glands and stone disease was a separate manifestation of primary hyperparathyroidism. Albright also showed that: 1) a renal threshold for calcium excretion was present in hypoparathyroid patients; 2) correction of hypocalcemia in hypoparathyroid patients with vitamin D had a phosphaturic action; 3) renal failure reduced the intestinal absorption of calcium in primary hyperparathyroidism; 4) the ''hungry bone'' syndrome developed after parathyroidectomy in severe primary hyperparathyroidism; and 5) a target organ can fail to respond to a hormone. He also suggested that a malignant tumor could be responsible for ectopic hormone production. Finally, our review integrates the observations of Albright with our current knowledge of calcium regulation and disorders.}, }
@article {pmid21621547, year = {2011}, author = {Oliveira, AG and Oliveira, CA}, title = {Epididymal lithiasis in roosters: in the middle of the way there was a stone.}, journal = {Life sciences}, volume = {89}, number = {15-16}, pages = {588-594}, doi = {10.1016/j.lfs.2011.04.021}, pmid = {21621547}, issn = {1879-0631}, mesh = {Animals ; Calcium/metabolism ; Chickens/*physiology ; Epididymis/*pathology ; Genitalia/physiology ; Homeostasis/physiology ; Infertility, Male/etiology/pathology/veterinary ; Lithiasis/*pathology/*veterinary ; Male ; Poultry Diseases/*pathology ; Reproduction/physiology ; Testicular Diseases/*pathology/*veterinary ; }, abstract = {The epididymal region plays an important role in the reproduction of roosters, as it is the site of functions important in the maintenance of fertility, including fluid and calcium reabsorption and sperm surface modifications. About 10 years ago, a reproductive dysfunction characterized by the formation of luminal calcium stones in the epididymal region of roosters was described. This anomaly, known as epididymal lithiasis, is associated with a significant decrease in the fertility of affected roosters. This reproductive anomaly has been observed in multiple countries and is thought to negatively impact the poultry industry; however, the cause of epididymal lithiasis has not been fully determined. Several hypotheses have been proposed to explain the origin of epididymal lithiasis, including the presence of an infectious agent within the epididymal region, an autoimmune response, increased dietary calcium and vitamin D3 intake and the presence of genetic susceptibility factors; however, none of these has been proven to be the primary cause of the calcium stone formation. Nonetheless, considerable evidence suggests that regardless of the primary cause of epididymal lithiasis, this anomaly could result from a hormonal imbalance or a local impairment of calcium homeostasis in the epididymal region. The objectives of this mini-review are to 1) summarize the reproductive alterations observed in animals affected by epididymal lithiasis, 2) discuss the hypotheses proposed to explain the cause of luminal stone formation and 3) provide perspectives for future studies of this reproductive disorder.}, }
@article {pmid21554525, year = {2011}, author = {Arrabal-Polo, MA and Arrabal-Martin, M and de Haro-Munoz, T and Lopez-Leon, VM and Merino-Salas, S and Ochoa-Hortal, MA and Garrido-Gomez, J and Lahoz-Garcia, C and Zuluaga-Gomez, A}, title = {Mineral density and bone remodelling markers in patients with calcium lithiasis.}, journal = {BJU international}, volume = {108}, number = {11}, pages = {1903-8; discussion 1908}, doi = {10.1111/j.1464-410X.2011.10167.x}, pmid = {21554525}, issn = {1464-410X}, mesh = {Adult ; Biomarkers/metabolism ; Bone Density/*physiology ; Bone Remodeling/*physiology ; Calcium/metabolism ; Female ; Femur ; Humans ; Hypercalciuria/complications/physiopathology ; Kidney Calculi/*etiology/physiopathology ; Lumbar Vertebrae ; Male ; Middle Aged ; Osteocalcin/metabolism ; }, abstract = {UNLABELLED: What's known on the subject? and What does the study add? Hypercalciuria is related with bone mineral density loss. This study demonstrates the relationship between recurrent calcium nephrolithiasis and bone mineral density loss and their correlation with bone markers.<br><br>OBJECTIVES: &#x2022;&#x2002;To show that a relationship exists between the loss of bone mineral density (BMD) and calcium renal lithiasis and that bone remodelling markers correlate with changes in BMD. &#x2022;&#x2002;It is possible that many cases hypercalciuria are related to the increase of bone turnover and the predominance of bone resorption phenomena.<br><br>PATIENTS AND METHODS: &#x2022;&#x2002;The present study comprised a transversal investigation in three groups: group O, without lithiasis; group A, with a single episode of lithiasis; and group B, with relapsed calcium renal lithiasis. &#x2022;&#x2002;An analysis was made of body mass index; abdominal X-ray and/or urography and renal ultrasonography; osteocalcin and &#x3b2;-crosslaps bone markers; calcium and citrate concentrations in the urine; and femur and spinal column bone densitometry. &#x2022;&#x2002;The results were analyzed by analysis of variance and Pearson's correlation coefficient.<br><br>RESULTS: &#x2022;&#x2002;Patients with relapsed calcium renal lithiasis present a greater BMD loss than those in the O or A groups. &#x2022;&#x2002;Densitometry: T-score femur -0.2 group O, -0.5 group A, -1.2 group B (P= 0.001); T-score column -0.6 group O, -0.6 group A, -1.3 group B (P= 0.05). &#x2022;&#x2002;A statistically significant negative correlation exists between values of &#x3b2;-crosslaps and T-score femur (R=-0.251; P= 0.009) and T-score column (R=-0.324; P= 0.001); thus, a higher concentration of &#x3b2;-crosslaps was accompanied by a lower value of the T-score and a greater loss of BMD. &#x2022;&#x2002;A positive relationship is observed between &#x3b2;-crosslaps and osteocalcin (R= 0.611; P < 0.001) and between calciuria and cocient &#x3b2;-crosslaps/osteocalcin (R= 0.303; P= 0.001).<br><br>CONCLUSIONS: &#x2022;&#x2002;A statistically significant relationship is shown between the loss of BMD and relapsed calcium renal lithiasis. &#x2022;&#x2002;Determination of bone remodelling markers (i.e. osteocalcin and &#x3b2;-crosslaps) facilitates the diagnosis of osteopaenia/osteoporosis in these patients.}, }
@article {pmid21544885, year = {2012}, author = {Tayefi-Nasrabadi, H and Sadigh-Eteghad, S and Aghdam, Z}, title = {The effects of the hydroalcohol extract of Rosa canina L. fruit on experimentally nephrolithiasic Wistar rats.}, journal = {Phytotherapy research : PTR}, volume = {26}, number = {1}, pages = {78-85}, doi = {10.1002/ptr.3519}, pmid = {21544885}, issn = {1099-1573}, mesh = {Animals ; Antioxidants/pharmacology/*therapeutic use ; Calcium/metabolism ; Calcium Oxalate/*metabolism ; Citric Acid/metabolism ; Dietary Supplements ; Drinking Water ; Ethylene Glycol ; Fruit ; Kidney/drug effects/metabolism ; Kidney Calculi/chemically induced/metabolism/*prevention &amp; control ; Lipid Peroxides/metabolism ; Liver/drug effects/metabolism ; Male ; *Phytotherapy ; Plant Extracts/pharmacology/*therapeutic use ; Potassium Citrate/administration &amp; dosage ; Random Allocation ; Rats ; Rats, Wistar ; Rosa/*chemistry ; }, abstract = {This research evaluated the possible therapeutic potential of Rosa canina (RC) as a preventive agent in experimentally induced calcium oxalate (CaOx) nephrolithiasis with ethylene glycol (1% EG) in rats. In this experiment, 50 Wistar rats were divided randomly into five groups (n = 10). These groups received tap drinking water (group I), 1% EG (group II), 250 mg/kg RC + 1% EG (group III), 500 mg/kg RC + 1% EG (group IV), or 2.5 g/kg potassium citrate + 1% EG (group V) for a period of 30 days. Blood and urine were collected for biochemical analysis, and the liver and kidneys were prepared for total lipid peroxides, calcium content and histological evaluation. The extract was analysed for total phenolics, flavonoids, ascorbic acid, citric acid and radical scavenger activity. The supplementation of the hydromethanol RC extract contributed to reducing the kidney and liver lipid peroxides to optimum levels in rats that had been treated with EG-induced CaOx lithiasis. The extract also decreased renal and urinary calcium contents, decreased the size and number of CaOx calculi in the kidneys, and significantly increased citrate excretion without changing the volume, pH, or urinary concentrations of oxalate in comparison with the control group. According to these results, RC can be useful as a preventive agent against the formation of CaOx kidney stones.}, }
@article {pmid21505756, year = {2012}, author = {Spivacow, FR and Negri, AL and del Valle, EE and Fradinger, E and Martinez, C and Polonsky, A}, title = {Persistence of hypercalciuria after successful surgical treatment for primary hyperparathyroidism.}, journal = {International urology and nephrology}, volume = {44}, number = {3}, pages = {857-863}, pmid = {21505756}, issn = {1573-2584}, mesh = {Aged ; Calcium/blood/urine ; Creatinine/blood/urine ; Female ; Humans ; Hypercalciuria/blood/complications/*etiology ; Hyperparathyroidism, Primary/complications/surgery/*urine ; Kidney Calculi/*etiology/urine ; Male ; Middle Aged ; Parathyroid Hormone/blood ; Parathyroidectomy ; Phosphorus/blood/urine ; Postoperative Period ; Preoperative Period ; Retrospective Studies ; }, abstract = {UNLABELLED: Primary hyperparathyroidism (PHPT) causes hypercalciuria and stone disease in a subset of patients. Hypercalciuria typically normalizes after surgery, although the risk of stone formation may persist up to 10 years. There are few reports in the literature that show persistent hypercalciuria despite normalization of serum calcium after parathyroid surgery. We retrospectively analyzed 111 patients with PHPT from the osteoporosis, and stone clinics seen between 1999 and 2006. We selected only patients who had a complete metabolic profile that included 24-hour collections before and at least 3 months after parathyroidectomy. We excluded patients who had creatinine clearance <60 ml/min/1.73 m(2). Fifty-four patients were selected for further analysis, 46 with baseline hypercalciuria and 8 with normocalciuria. Changes in filtered load of calcium and fractional excretion of calcium were evaluated before and after parathyroid surgery. Total and ionized calcium and phosphorus normalized in all patients after surgery (24 ± 19 months); fractional excretion of calcium decreased, but did not normalize. Hypercalciuria persisted after surgery in 30.7% (n = 12/39) of the women and 50% (n = 4/8) of men. Of the patients in whom calciuria normalized after parathyroidectomy, 43.3% (n = 13/30) had kidney stones before surgery, whereas kidney stones were present in 87.5% (n = 14/16) in those in whom hypercalciuria persisted postsurgery. In hypercalciuric men and women before surgery in whom hypercalciuria persisted after surgery, fractional excretion of calcium was significantly higher than that in patients with normocalciuria.<br><br>CONCLUSIONS: Persistently increased fractional excretion of calcium could explain the sustained increased risk of stone disease in patients with PHPT for many years after successful parathyroidectomy.}, }
@article {pmid21441130, year = {2011}, author = {Letavernier, E and Traxer, O and Daudon, M and Tligui, M and Hubert-Brierre, J and Guerrot, D and Sebag, A and Baud, L and Haymann, JP}, title = {Determinants of osteopenia in male renal-stone-disease patients with idiopathic hypercalciuria.}, journal = {Clinical journal of the American Society of Nephrology : CJASN}, volume = {6}, number = {5}, pages = {1149-1154}, pmid = {21441130}, issn = {1555-905X}, mesh = {Adult ; *Bone Diseases, Metabolic/diagnosis/epidemiology/metabolism ; Calcification, Physiologic ; Calcium/blood/urine ; Calcium, Dietary/administration &amp; dosage/pharmacokinetics ; Humans ; *Hypercalciuria/diagnosis/epidemiology/metabolism ; *Kidney Calculi/diagnosis/epidemiology/metabolism ; Logistic Models ; Male ; Middle Aged ; *Osteoporosis/diagnosis/epidemiology/metabolism ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; }, abstract = {BACKGROUND AND OBJECTIVES: Bone demineralization is frequent in renal-stone formers with hypercalciuria. Although this pathologic link has been recognized for decades, the underlying mechanisms and risk factors associated with osteopenia/osteoporosis in this population remain partially understood.<br><br>This study retrospectively analyzed determinants of low bone mineral density (BMD) in 65 idiopathic hypercalciuric male renal-stone formers. Clinical and biologic evaluation included BMD measurement, bone-remodeling markers, analysis of calcium metabolism with oral calcium load test, and dietary inquiry.<br><br>RESULTS: Patients with osteopenia (n=23, 35% of the population) presented significantly higher fasting calciuria as compared with normal bone density patients (n=42) (calcium/creatinine ratio was 0.32 versus 0.24 mmol/mmol; P=0.006). Analysis of the whole population revealed a negative association between fasting hypercalciuria and BMD (P = 0.003), independent of confounding variables including body-mass index and tobacco consumption. The fasting calcium/creatinine ratio above 0.25 mmol/mmol was associated with a 3.8-fold increase in the risk of low BMD.<br><br>CONCLUSION: In our study, fasting hypercalciuria after a 2-day calcium-restricted diet appears as the only biologic factor associated with low BMD, suggesting a bone-calcium efflux. Our results support the view of a parathyroid-independent pathologic process that remains to be identified. Hypercalciuric patients with low BMD do not excrete more calcium in 24-hour urine samples than patients without low BMD.}, }
@article {pmid21435718, year = {2011}, author = {Petersen, OH and Gerasimenko, OV and Tepikin, AV and Gerasimenko, JV}, title = {Aberrant Ca(2+) signalling through acidic calcium stores in pancreatic acinar cells.}, journal = {Cell calcium}, volume = {50}, number = {2}, pages = {193-199}, doi = {10.1016/j.ceca.2011.02.010}, pmid = {21435718}, issn = {1532-1991}, support = {G0300076/MRC_/Medical Research Council/United Kingdom ; G0700167/MRC_/Medical Research Council/United Kingdom ; G8801575/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Acids/*metabolism ; Acinar Cells/*metabolism ; Bile Acids and Salts/metabolism ; Calcium/*metabolism ; *Calcium Signaling ; Cholecystokinin/metabolism ; Cyclic ADP-Ribose/metabolism ; Endoplasmic Reticulum/drug effects/metabolism ; Fatty Acids, Monounsaturated/pharmacology ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; NADP/analogs &amp; derivatives/pharmacology ; Pancreas, Exocrine/*cytology/metabolism ; Pancreatitis/metabolism/pathology ; Secretory Vesicles/metabolism ; Vacuolar Proton-Translocating ATPases/metabolism ; }, abstract = {Pancreatic acinar cells possess a very large Ca(2+) store in the endoplasmic reticulum, but also have extensive acidic Ca(2+) stores. Whereas the endoplasmic reticulum is principally located in the baso-lateral part of the cells, although with extensions into the granular area, the acidic stores are exclusively present in the apical part. The two types of stores can be differentiated pharmacologically because the endoplasmic reticulum accumulates Ca(2+) via SERCA pumps, whereas the acidic pools require functional vacuolar H(+) pumps in order to maintain a high intra-organellar Ca(2+) concentration. The human disease acute pancreatitis is initiated by trypsinogen activation in the apical pole and this is mostly due to either complications arising from gall bladder stones or excessive alcohol consumption. Attention has therefore been focussed on assessing the acute effects of bile acids as well as alcohol metabolites. The evidence accumulated so far indicates that bile acids and fatty acid ethyl esters - the non-oxidative products of alcohol and fatty acids - exert their pathological effects primarily by excessive Ca(2+) release from the acidic stores. This occurs by opening of the very same release channels that are also responsible for normal stimulus-secretion coupling, namely inositol trisphosphate and ryanodine receptors. The inositol trisphosphate receptors are of particular importance and the results of gene deletion experiments indicate that the fatty acid ethyl esters mainly utilize sub-types 2 and 3.}, }
@article {pmid21422754, year = {2011}, author = {Telci, D and Dogan, AU and Ozbek, E and Polat, EC and Simsek, A and Cakir, SS and Yeloglu, HO and Sahin, F}, title = {KLOTHO gene polymorphism of G395A is associated with kidney stones.}, journal = {American journal of nephrology}, volume = {33}, number = {4}, pages = {337-343}, doi = {10.1159/000325505}, pmid = {21422754}, issn = {1421-9670}, mesh = {Adult ; Alleles ; Calcium/metabolism ; Exons ; Female ; Genotype ; Glucuronidase/*genetics ; Humans ; Kidney Calculi/*genetics ; Klotho Proteins ; Male ; Middle Aged ; Phosphates/metabolism ; *Polymorphism, Genetic ; Risk ; Risk Factors ; }, abstract = {BACKGROUND/AIMS: KLOTHO, a type-1 transmembrane protein with glucurodinase activity, is expressed in tissues responsible for calcium homeostasis such as the kidney, parathyroid gland and the epithelium of the choroid plexus in the brain. Given the emerging evidence indicating a novel regulatory function for KLOTHO protein in renal calcium and phosphate homeostasis, the present study aims to investigate the association between KLOTHO genetic polymorphisms and kidney stone (KS).<br><br>METHODS: KLOTHO gene polymorphisms G395A in the promoter region, F252V in exon 2, and C1818T in exon 4 were investigated in 108 patients with renal calcium stone formation and 51 age-matched healthy volunteers with no history of renal stone formation, using polymerase chain reaction.<br><br>RESULTS: GG genotype of G395A KLOTHO polymorphism had approximately 2-fold increased KS risk compared with the homozygous genotype AA and heterozygote GA (OR 1.849, 95% CI 1.016-3.364, p = 0.044). We also found that non-A allele carriers had significantly higher KS risk associated with the KS clinical characteristics including hypercalcemia, hypophosphatemia and phosphaturia.<br><br>CONCLUSION: Our findings suggested that the G395A polymorphism of KLOTHO gene is associated with the KSs and may act as a risk factor for the development of KS disease.}, }
@article {pmid21420116, year = {2011}, author = {Chou, YH and Juo, SH and Chiu, YC and Liu, ME and Chen, WC and Chang, CC and Chang, WP and Chang, JG and Chang, WC}, title = {A polymorphism of the ORAI1 gene is associated with the risk and recurrence of calcium nephrolithiasis.}, journal = {The Journal of urology}, volume = {185}, number = {5}, pages = {1742-1746}, doi = {10.1016/j.juro.2010.12.094}, pmid = {21420116}, issn = {1527-3792}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Calcium/*metabolism ; Calcium Channels/*genetics ; Calcium Signaling/*genetics ; Case-Control Studies ; Chi-Square Distribution ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Nephrolithiasis/*genetics ; ORAI1 Protein ; *Polymorphism, Single Nucleotide ; Recurrence ; Risk ; Taiwan ; }, abstract = {PURPOSE: Store-operated calcium entry has been considered an important factor to regulate inflammatory reactions in nonexcitable cells. However, the effects of genetic polymorphisms of ORAI1, a main component of store-operated calcium channels, on nephrolithiasis and stone recurrence remain unclear. We investigated the association between calcium containing nephrolithiasis and genetic variants of ORAI1 gene in Taiwanese patients.<br><br>MATERIALS AND METHODS: A case-control study was performed in 136 patients with nephrolithiasis and 500 controls. Five tagging single nucleotide polymorphisms of ORAI1 were selected for genotyping. ORAI1 genotypes were determined by TaqMan&#xae; assay. Hardy-Weinberg equilibrium in cases and controls was assessed, and genetic effects were evaluated by the chi-square test and sliding window haplotype analysis. Subset analysis was done according to family history.<br><br>RESULTS: Two single nucleotide polymorphisms (rs12313273 and rs6486795) of the ORAI1 gene were associated with the risk of nephrolithiasis. The C allele carrier for rs12313273 was strongly related to recurrent stone forming in patients. On sliding window analysis the results of the 2 (rs12313273 and rs7135617) and the 3 (rs12313273, rs7135617 and rs6486795) single nucleotide polymorphism haplotypes had more significant effects on the risk of nephrolithiasis than the single nucleotide polymorphism rs12313273.<br><br>CONCLUSIONS: To our knowledge this is the first study identifying the novel polymorphisms of the ORAI1 gene, which may predispose to the risk of calcium nephrolithiasis and disease recurrence.}, }
@article {pmid21340610, year = {2011}, author = {Gürgöze, MK and Sarı, MY}, title = {Results of medical treatment and metabolic risk factors in children with urolithiasis.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {26}, number = {6}, pages = {933-937}, pmid = {21340610}, issn = {1432-198X}, mesh = {Adolescent ; Calcium Metabolism Disorders/complications/*diet therapy/metabolism ; Child ; Child, Preschool ; Citric Acid/urine ; Cystinuria/diagnosis/urine ; Female ; Humans ; Hypercalciuria/diagnosis/urine ; Hyperoxaluria/diagnosis/urine ; Infant ; Male ; Phosphates/urine ; Prospective Studies ; Risk Factors ; Treatment Outcome ; Uric Acid/urine ; Urinalysis ; Urolithiasis/complications/*diet therapy/metabolism ; }, abstract = {Data on conservative treatment in children with urolithiasis are limited. The aim of the study was to determine the metabolic etiology and results of conservative treatment in children with urolithiasis. We evaluated the clinical presentation and metabolic features of 112 children with urolithiasis. The mean age at diagnosis of urolithiasis was 3.9 (range 0.1-18) years, and follow-up duration was 16.7 (range 1-36) months. The most common presenting symptoms were flank or abdominal pain and restlessness (25%). Urine analysis revealed metabolic abnormalities in 92% of cases, including hypocitraturia (42%), hyperoxaluria (32.1%), hypercalcuria (25%), hyperuricosuria (9.8%), and cystinuria (2.7%). Patients who had metabolic risk factors were treated according to underlying metabolic abnormalities. About half of these patients were stone free or stones were diminished in size. These results showed that early recognition and treatment of urinary metabolic abnormalities will reduce the number of invasive procedures and renal damage in children with urolithiasis.}, }
@article {pmid21329669, year = {2011}, author = {Chutipongtanate, S and Thongboonkerd, V}, title = {Ceftriaxone crystallization and its potential role in kidney stone formation.}, journal = {Biochemical and biophysical research communications}, volume = {406}, number = {3}, pages = {396-402}, doi = {10.1016/j.bbrc.2011.02.053}, pmid = {21329669}, issn = {1090-2104}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/*chemistry/pharmacokinetics ; Calcium/chemistry/metabolism ; Ceftriaxone/administration &amp; dosage/*chemistry/pharmacokinetics ; Cell Adhesion ; Cell Line ; Crystallization ; Dogs ; Humans ; Kidney Calculi/*chemistry ; Nephrolithiasis/*chemically induced ; }, abstract = {Drug-induced nephrolithiasis contributes to 1-2% of the incidence of renal calculi. We examined whether ceftriaxone at therapeutic doses could be crystallized in the urine and also explored its role in kidney stone formation. Crystallization was induced by mixing ceftriaxone sodium at therapeutic urinary excretion levels (0.5-4.0 mg/ml) to calcium chloride at physiologic urinary concentration (5mM) in deionized (dI) water or artificial urine (AU). The results showed that ceftriaxone was crystallized with free calcium in dose- and time-dependent manner. These ceftriaxone/calcium crystals showed birefringence property under polarized microscope. Individual crystals had needle-shape (5-100 μm in length), whereas the aggregated form had star-burst and irregular-plate shape (40-200 μm in diameter) (note that the crystal sizes were much larger than renal tubular lumens). Calcium-depletion assay revealed that crystallization required free calcium as a substrate. In AU, crystallization remained although it was partially inhibited when compared to that in dI water. Finally, these crystals could tightly adhere onto renal tubular cell surface. Our data demonstrated that ceftriaxone at therapeutic levels could be crystallized with free calcium in the urine under physiologic condition. We hypothesize that tubular occlusion and crystal-cell adhesion may play important role in pathogenic mechanisms of ceftriaxone-induced nephrolithiasis.}, }
@article {pmid21289988, year = {2011}, author = {Zeng, J and Yang, F and Zhang, W and Gong, Q and Du, Y and Ling, J}, title = {Association between dental pulp stones and calcifying nanoparticles.}, journal = {International journal of nanomedicine}, volume = {6}, number = {}, pages = {109-118}, pmid = {21289988}, issn = {1178-2013}, mesh = {Adult ; Calcium/*chemistry/metabolism ; Culture Techniques ; *Dental Pulp Calcification ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunohistochemistry ; Microscopy, Electron, Transmission ; Middle Aged ; Nanoparticles/*chemistry ; Phosphates/chemistry/metabolism ; }, abstract = {The etiology of dental pulp stones, one type of extraskeletal calcification disease, remains elusive to date. Calcifying nanoparticles (CNPs), formerly referred to as nanobacteria, were reported to be one etiological factor in a number of extraskeletal calcification diseases. We hypothesized that CNPs are involved in the calcification of the dental pulp tissue, and therefore investigated the link between CNPs and dental pulp stones. Sixty-five freshly collected dental pulp stones, each from a different patient, were analyzed. Thirteen of the pulp stones were examined for the existence of CNPs in situ by immunohistochemical staining (IHS), indirect immunofluorescence staining (IIFS), and transmission electron microscope (TEM). The remaining 52 pulp stones were used for isolation and cultivation of CNPs; the cultured CNPs were identified and confirmed via their shape and growth characteristics. Among the dental pulp stones examined in situ, 84.6% of the tissue samples staines positive for CNPs antigen by IHS; the corresponding rate by IIFS was 92.3 %. In 88.2% of the cultured samples, CNPs were isolated and cultivated successfully. The CNPs were visible under TEM as 200-400 nm diameter spherical particles surrounded by a compact crust. CNPs could be detected and isolated from a high percentage of dental pulp stones, suggesting that CNPs might play an important role in the calcification of dental pulp.}, }
@article {pmid21170867, year = {2010}, author = {Petrazzuolo, O and Trepiccione, F and Zacchia, M and Capasso, G}, title = {Hypertension and renal calcium transport.}, journal = {Journal of nephrology}, volume = {23 Suppl 16}, number = {}, pages = {S112-7}, pmid = {21170867}, issn = {1121-8428}, mesh = {Animals ; Calcium/*metabolism ; Disease Models, Animal ; Humans ; Hypercalciuria/etiology ; Hypertension/complications/*metabolism ; Ion Transport ; Kidney/*metabolism ; Parathyroid Hormone/metabolism ; }, abstract = {Calcium homeostasis is altered in hypertensive patients. Indeed several investigators have reported that sodium-sensitive hypertension is associated with hypercalciuria. On the other hand, an independent clinical association exists between the occurrence of urolithiasis and hypertension, but the molecular mechanism(s) involved in stone formation by high blood pressure have not been so far clarified. To understand this association, it is obvious that we should analyze the effect of hypertension on the transport proteins involved in the renal calcium handling. In the kidney, the tubular reabsorption of calcium may proceed through transcellular and paracellular routes. At variance with the proximal tubule, along the distal segment, calcium transport is entirely sodium independent and occurs via the transcellular pathway. In particular, transcellular calcium reabsorption proceeds through a well-controlled sequence of events consisting of luminal calcium entry via the epithelial calcium channel (TRPV5), cytosolic diffusion of calcium bound to calbindin-D28K, and basolateral extrusion of calcium through the Na/Ca exchanger (NCX1) and plasma membrane Ca-ATPase (PMCA). It is highly likely that these proteins may be altered in hypertensive disease thus justifying and explaining the reported hypercalciuria. Experiments in hypertensive strains of animals exhibiting hypercalciuria may help to solve this puzzle.}, }
@article {pmid21272865, year = {2011}, author = {Swaddiwudhipong, W and Mahasakpan, P and Limpatanachote, P and Krintratun, S}, title = {An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: a population study.}, journal = {Environmental research}, volume = {111}, number = {4}, pages = {579-583}, doi = {10.1016/j.envres.2011.01.007}, pmid = {21272865}, issn = {1096-0953}, mesh = {Adolescent ; Adult ; Aged ; Cadmium/*urine ; Environmental Exposure/statistics &amp; numerical data ; Environmental Pollutants/*urine ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Thailand/epidemiology ; Urinary Calculi/*epidemiology/urine ; Young Adult ; }, abstract = {Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinary excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population.}, }
@article {pmid21179406, year = {2010}, author = {Chadwick, W and Zhou, Y and Park, SS and Wang, L and Mitchell, N and Stone, MD and Becker, KG and Martin, B and Maudsley, S}, title = {Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses.}, journal = {PloS one}, volume = {5}, number = {12}, pages = {e14352}, pmid = {21179406}, issn = {1932-6203}, support = {//Intramural NIH HHS/United States ; }, mesh = {Aging ; Brain-Derived Neurotrophic Factor/metabolism ; Calcium/metabolism ; Cell Line, Tumor/drug effects ; Gene Expression Regulation ; Genomics ; Homeostasis ; Humans ; Hydrogen Peroxide/pharmacology ; Ligands ; Models, Biological ; Neurons/*metabolism ; Oxidative Stress ; Peroxides/*chemistry ; Proteomics/methods ; }, abstract = {Oxidative exposure of cells occurs naturally and may be associated with cellular damage and dysfunction. Protracted low level oxidative exposure can induce accumulated cell disruption, affecting multiple cellular functions. Accumulated oxidative exposure has also been proposed as one of the potential hallmarks of the physiological/pathophysiological aging process. We investigated the multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural cells to understand how they respond to the continued presence of oxidative stressors. We show that minimal protracted oxidative stresses induce complex molecular and physiological alterations in cell functionality. Upon chronic exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a multifactorial response to the stressor. To fully appreciate the peroxide-mediated cellular effects, we assessed these adaptive effects at the genomic, proteomic and cellular signal processing level. Combined analyses of these multiple levels of investigation revealed a complex cellular adaptive response to the protracted peroxide exposure. This adaptive response involved changes in cytoskeletal structure, energy metabolic shifts towards glycolysis and selective alterations in transmembrane receptor activity. Our analyses of the global responses to chronic stressor exposure, at multiple biological levels, revealed a viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations.}, }
@article {pmid21123491, year = {2011}, author = {Hering-Smith, KS and Schiro, FR and Pajor, AM and Hamm, LL}, title = {Calcium sensitivity of dicarboxylate transport in cultured proximal tubule cells.}, journal = {American journal of physiology. Renal physiology}, volume = {300}, number = {2}, pages = {F425-32}, pmid = {21123491}, issn = {1522-1466}, support = {DK54952/DK/NIDDK NIH HHS/United States ; P20RR017659/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Cells, Cultured ; Citrates/metabolism ; Dicarboxylic Acid Transporters/*metabolism ; Kidney Tubules, Proximal/*metabolism ; Opossums ; Rabbits ; Succinic Acid/metabolism ; }, abstract = {Urinary citrate is an important inhibitor of calcium nephrolithiasis and is primarily determined by proximal tubule reabsorption. The major transporter to reabsorb citrate is Na(+)-dicarboxylate cotransporter (NaDC1), which transports dicarboxylates, including the divalent form of citrate. We previously found that opossum kidney (OK) proximal tubule cells variably express either divalent or trivalent citrate transport, depending on extracellular calcium. The present studies were performed to delineate the mechanism of the effect of calcium on citrate and succinate transport in these cells. Transport was measured using isotope uptake assays. In some studies, NaDC1 transport was studied in Xenopus oocytes, expressing either the rabbit or opossum ortholog. In the OK cell culture model, lowering extracellular calcium increased both citrate and succinate transport by more than twofold; the effect was specific in that glucose transport was not altered. Citrate and succinate were found to reciprocally inhibit transport at low extracellular calcium (<60 μM), but not at normal calcium (1.2 mM); this mutual inhibition is consistent with dicarboxylate transport. The inhibition varied progressively at intermediate levels of extracellular calcium. In addition to changing the relative magnitude and interaction of citrate and succinate transport, decreasing calcium also increased the affinity of the transport process for various other dicarboxylates. Also, the affinity for succinate, at low concentrations of substrate, was increased by calcium removal. In contrast, in oocytes expressing NaDC1, calcium did not have a similar effect on transport, indicating that NaDC1 could not likely account for the findings in OK cells. In summary, extracellular calcium regulates constitutive citrate and succinate transport in OK proximal tubule cells, probably via a novel transport process that is not NaDC1. The calcium effect on citrate transport parallels in vivo studies that demonstrate the regulation of urinary citrate excretion with urinary calcium excretion, a process that may be important in decreasing urinary calcium stone formation.}, }
@article {pmid21123489, year = {2011}, author = {Bergsland, KJ and Zisman, AL and Asplin, JR and Worcester, EM and Coe, FL}, title = {Evidence for net renal tubule oxalate secretion in patients with calcium kidney stones.}, journal = {American journal of physiology. Renal physiology}, volume = {300}, number = {2}, pages = {F311-8}, pmid = {21123489}, issn = {1522-1466}, support = {P01 DK056788/DK/NIDDK NIH HHS/United States ; P01 DK56788/DK/NIDDK NIH HHS/United States ; UL1 RR024999/RR/NCRR NIH HHS/United States ; }, mesh = {Adult ; Calcium/metabolism ; Diet ; Female ; Humans ; Hypercalciuria/*metabolism ; Kidney Calculi/*metabolism ; Kidney Tubules/*metabolism ; Male ; Middle Aged ; Oxalates/blood/*metabolism ; }, abstract = {Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range.}, }
@article {pmid21091994, year = {2010}, author = {Wu, Z and Shen, W}, title = {Progesterone inhibits L-type calcium currents in gallbladder smooth muscle cells.}, journal = {Journal of gastroenterology and hepatology}, volume = {25}, number = {12}, pages = {1838-1843}, doi = {10.1111/j.1440-1746.2010.06299.x}, pmid = {21091994}, issn = {1440-1746}, mesh = {Adenylyl Cyclases/metabolism ; Animals ; Calcium/*metabolism ; Calcium Channel Blockers/*pharmacology ; Calcium Channels, L-Type/*drug effects/metabolism ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/antagonists &amp; inhibitors/metabolism ; Dose-Response Relationship, Drug ; Enzyme Activation ; Enzyme Activators/pharmacology ; Gallbladder/cytology/*drug effects/metabolism ; Guinea Pigs ; In Vitro Techniques ; Male ; Membrane Potentials ; Myocytes, Smooth Muscle/*drug effects/metabolism ; Patch-Clamp Techniques ; Potassium/metabolism ; Progesterone/*pharmacology ; Protein Kinase Inhibitors/pharmacology ; Time Factors ; }, abstract = {BACKGROUND AND AIM: The incidence of gallbladder stones is higher in women during pregnancy than in men. Progesterone can inhibit gallbladder motility and facilitate gallstone formation. However, the ionic mechanisms have not been fully illuminated. This study sought to investigate the effects of progesterone on L-type calcium currents and voltage-dependent potassium currents in gallbladder smooth muscle cells.<br><br>METHODS: Gallbladder smooth muscle cells were isolated by enzymatic digestion from adult guinea pigs. Ionic currents were recorded by the whole-cell patch clamp method.<br><br>RESULTS: Progesterone inhibited L-type calcium currents in a concentration-dependent manner. The characteristic of current-voltage curve was not significantly altered. The amplitude of calcium currents was gradually suppressed, reached a steady-state level within 4-6 min, and restored partly after washout. In the presence of protein kinase A (PKA) inhibitor, Rp-cAMP, the inhibitory effect induced by progesterone was apparently attenuated, whereas forskolin, a direct activator of adenylate cyclase, could suppress L-type calcium channel. However, progesterone did not significantly affect voltage-dependent potassium currents.<br><br>CONCLUSIONS: Progesterone inhibits L-type calcium channel by cAMP/PKA pathway in gallbladder smooth muscle cells. This may be an important mechanism for the gallbladder hypomotility induced by progesterone.}, }
@article {pmid21051502, year = {2011}, author = {Rendina, D and De Filippo, G and Zampa, G and Muscariello, R and Mossetti, G and Strazzullo, P}, title = {Characteristic clinical and biochemical profile of recurrent calcium-oxalate nephrolithiasis in patients with metabolic syndrome.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {26}, number = {7}, pages = {2256-2263}, doi = {10.1093/ndt/gfq664}, pmid = {21051502}, issn = {1460-2385}, mesh = {Adult ; Calcium/*metabolism ; Calcium Oxalate/*chemistry ; *Diet, Sodium-Restricted ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Kidney Function Tests ; Male ; Metabolic Syndrome/*complications ; Middle Aged ; Nephrolithiasis/*etiology ; Oxalates/*metabolism ; Prognosis ; Recurrence ; Risk Factors ; }, abstract = {BACKGROUND: Metabolic syndrome is a risk factor for nephrolithiasis. This study was performed to evaluate the clinical and biochemical profile of calcium-oxalate nephrolithiasis in stone formers with metabolic syndrome.<br><br>METHODS: A total of 526 recurrent stone formers, 184 of them with metabolic syndrome, and 214 controls were examined on a free diet and after a sodium-restricted diet (sodium intake < 100 mmol/24 h).<br><br>RESULTS: On free diet, stone formers with metabolic syndrome showed higher sodium excretion [mean (95% confidence interval), 196 (176-218) vs 160 (150-168) mmol/24 h; P < 0.01] and lower citrate excretion [2.23 (1.99-2.58) vs 2.84 (2.51-3.17) mmol/24 h; P < 0.01] compared to controls, whereas stone formers without metabolic syndrome showed higher calcium and oxalate excretion [5.43 (5.01-5.82) vs 3.58 (2.84-4.19) and 0.34 (0.32-0.36) vs 0.26 (0.20-0.31)m mmol/24 h for calcium and oxalate, respectively; P < 0.01] and lower citrate excretion [2.18 (1.98-2.38) vs 2.84 (2.51-3.17) mmol/24 h; P < 0.01] compared to controls. The ion activity product of urinary calcium-oxalate salts was similar between stone formers with and without metabolic syndrome [1.41 (1.31-1.59) vs 1.40 (1.35-1.45); P > 0.05]. After the test diet, this index was lower in diet-compliant stone formers with metabolic syndrome compared to diet-compliant stone formers without metabolic syndrome [1.15 (1.10-1.21) vs 1.39 (1.31-1.45); P < 0.01].<br><br>CONCLUSIONS: The biochemical profiles and responses to the sodium-restricted diet were significantly different between stone formers with metabolic syndrome and those without. Dietary habits play a central role in the pathogenesis of nephrolithiasis in stone formers with metabolic syndrome.}, }
@article {pmid20962745, year = {2011}, author = {Vezzoli, G and Terranegra, A and Arcidiacono, T and Soldati, L}, title = {Genetics and calcium nephrolithiasis.}, journal = {Kidney international}, volume = {80}, number = {6}, pages = {587-593}, doi = {10.1038/ki.2010.430}, pmid = {20962745}, issn = {1523-1755}, mesh = {Calcium/*metabolism ; Gene Expression Profiling ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Kidney Calculi/chemistry/genetics ; Models, Biological ; Nephrocalcinosis/genetics/metabolism ; Nephrolithiasis/*genetics/*metabolism ; Receptors, Calcium-Sensing/genetics ; }, abstract = {Calcium nephrolithiasis is one of the most prevalent uronephrologic disorders in the western countries. Studies in families and twins evidenced a genetic predisposition to calcium nephrolithiasis. Family-based or case-control studies of single-candidate genes evidenced the possible involvement of calcium-sensing receptor (CASR), vitamin D receptor (VDR), and osteopontin (OPN) gene polymorphisms in stone formation. The only high-throughput genome-wide association study identified claudin 14 (CLDN14) gene as a possible major gene of nephrolithiasis. Specific phenotypes were related with these genes: CASR gene in normocitraturic patients, VDR gene in hypocitraturic patients with severe clinical course, and CLDN14 gene in hypercalciuric patients. The pathogenetic weight of these genes remains unclear, but an alteration of their expression may occur in stone formers. Technological skills, accurate clinical examination, and a detailed phenotype description are the basis to get new insight about the genetic basis of nephrolithiasis.}, }
@article {pmid20947503, year = {2010}, author = {Touchberry, CD and Bales, IK and Stone, JK and Rohrberg, TJ and Parelkar, NK and Nguyen, T and Fuentes, O and Liu, X and Qu, CK and Andresen, JJ and Valdivia, HH and Brotto, M and Wacker, MJ}, title = {Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) potentiates cardiac contractility via activation of the ryanodine receptor.}, journal = {The Journal of biological chemistry}, volume = {285}, number = {51}, pages = {40312-40321}, pmid = {20947503}, issn = {1083-351X}, support = {R01 HL055438/HL/NHLBI NIH HHS/United States ; 1RC2AR058962-0110/AR/NIAMS NIH HHS/United States ; R0I-HL055438/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Fluorescent Dyes/pharmacology ; Fura-2/pharmacology ; Homeostasis/drug effects/physiology ; Hypoglycemic Agents/pharmacology ; Insulin/pharmacology ; Lipid Bilayers/metabolism ; Mice ; Mice, Knockout ; Muscle Proteins/genetics/*metabolism ; Myocardial Contraction/drug effects/*physiology ; Myocytes, Cardiac/cytology/*metabolism ; Phosphatidylinositol Phosphates/genetics/*metabolism ; Phosphoric Monoester Hydrolases/genetics/metabolism ; Ryanodine/pharmacology ; Ryanodine Receptor Calcium Release Channel/genetics/*metabolism ; Sarcoplasmic Reticulum/genetics/metabolism ; }, abstract = {Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is the most recently identified phosphoinositide, and its functions have yet to be fully elucidated. Recently, members of our muscle group have shown that PI(3,5)P2 plays an important role in skeletal muscle function by altering Ca(2+) homeostasis. Therefore, we hypothesized that PI(3,5)P2 may also modulate cardiac muscle contractility by altering intracellular Ca(2+) ([Ca(2+)](i)) in cardiac myocytes. We first confirmed that PI(3,5)P2 was present and increased by insulin treatment of cardiomyocytes via immunohistochemistry. To examine the acute effects of PI(3,5)P2 treatment, electrically paced left ventricular muscle strips were incubated with PI(3,5)P2. Treatment with PI(3,5)P2 increased the magnitude of isometric force, the rate of force development, and the area associated with the contractile waveforms. These enhanced contractile responses were also observed in MIP/Mtmr14(-/-) mouse hearts, which we found to have elevated levels of PI(3,5)P2. In cardiac myocytes loaded with fura-2, PI(3,5)P2 produced a robust elevation in [Ca(2+)](i). The PI(3,5)P2-induced elevation of [Ca(2+)](i) was not present in conditions free of extracellular Ca(2+) and was completely blocked by ryanodine. We investigated whether the phosphoinositide acted directly with the Ca(2+) release channels of the sarcoplasmic reticulum (ryanodine receptors; RyR2). PI(3,5)P2 increased [(3)H]ryanodine binding and increased the open probability (P(o)) of single RyR2 channels reconstituted in lipid bilayers. This strongly suggests that the phosphoinositide binds directly to the RyR2 channel. Thus, we provide inaugural evidence that PI(3,5)P2 is a powerful activator of sarcoplasmic reticulum Ca(2+) release and thereby modulates cardiac contractility.}, }
@article {pmid20881241, year = {2010}, author = {Elizondo, MR and Budi, EH and Parichy, DM}, title = {trpm7 regulation of in vivo cation homeostasis and kidney function involves stanniocalcin 1 and fgf23.}, journal = {Endocrinology}, volume = {151}, number = {12}, pages = {5700-5709}, pmid = {20881241}, issn = {1945-7170}, support = {F31 DK074369/DK/NIDDK NIH HHS/United States ; P01 GM078195/GM/NIGMS NIH HHS/United States ; R01 HD040165/HD/NICHD NIH HHS/United States ; R01 HD40165/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Calcium/*metabolism ; Embryo, Nonmammalian ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors/genetics/*metabolism ; Gene Expression Regulation, Developmental/physiology ; Glycoproteins/genetics/*metabolism ; Homeostasis/physiology ; Kidney/*physiology ; Larva ; Magnesium/*metabolism ; Mutation ; Protein Serine-Threonine Kinases ; TRPM Cation Channels/genetics/*metabolism ; Zebrafish ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {The transient receptor potential melastatin 7 (trpm7) channel kinase is a primary regulator of magnesium homeostasis in vitro. Here we show that trpm7 is an important regulator of cation homeostasis as well as kidney function in vivo. Using zebrafish trpm7 mutants, we show that early larvae exhibit reduced levels of both total magnesium and total calcium. Accompanying these deficits, we show that trpm7 mutants express higher levels of stanniocalcin 1 (stc1), a potent regulator of calcium homeostasis. Using transgenic overexpression and morpholino oligonucleotide knockdown, we demonstrate that stc1 modulates both calcium and magnesium levels in trpm7 mutants and in the wild type and that levels of these cations are restored to normal in trpm7 mutants when stc1 activity is blocked. Consistent with defects in both calcium and phosphate homeostasis, we further show that trpm7 mutants develop kidney stones by early larval stages and exhibit increased levels of the anti-hyperphosphatemic factor, fibroblast growth factor 23 (fgf23). Finally, we demonstrate that elevated fgf23 expression contributes to kidney stone formation by morpholino knockdown of fgf23 in trpm7 mutants. Together, these analyses reveal roles for trpm7 in regulating cation homeostasis and kidney function in vivo and implicate both stc1 and fgf23 in these processes.}, }
@article {pmid20842614, year = {2010}, author = {Knight, J and Assimos, DG and Easter, L and Holmes, RP}, title = {Metabolism of fructose to oxalate and glycolate.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {42}, number = {12}, pages = {868-873}, pmid = {20842614}, issn = {1439-4286}, support = {R01 DK073732-04/DK/NIDDK NIH HHS/United States ; R01 DK73732/DK/NIDDK NIH HHS/United States ; R01 DK073732/DK/NIDDK NIH HHS/United States ; M01 RR007122/RR/NCRR NIH HHS/United States ; M01 RR07122/RR/NCRR NIH HHS/United States ; }, mesh = {Adult ; Calcium/metabolism ; Calcium Oxalate/urine ; Female ; Fructose/adverse effects/*metabolism ; Glycolates/*metabolism ; Hep G2 Cells ; Humans ; Kidney Calculi/etiology/metabolism ; Male ; Oxalates/*metabolism/urine ; Risk Factors ; }, abstract = {Much attention has been recently directed at fructose consumption because of its association with obesity and subsequent development of chronic diseases. It was recently reported that an increased fructose intake increases the risk of forming kidney stones. It was postulated that fructose consumption may increase urinary oxalate, a risk factor for calcium oxalate kidney stone disease. However, conflicting results have been obtained in human studies examining the relationship between fructose metabolism and oxalate synthesis. To test whether fructose intake influences urinary excretions impacting kidney stone risk, healthy subjects consumed diets controlled in their contents of fructose, oxalate, calcium, and other nutrients. Subjects consumed diets containing 4, 13, and 21% of calories as fructose in a randomized order. No changes in the excretions of oxalate, calcium, and uric acid were observed. In vitro investigations with cultured liver cells incubated with (13)C-labeled sugars indicated that neither fructose nor glucose was converted to oxalate by these cells. Fructose metabolism accounted for 12.4 ± 1.6% of the glycolate detected in the culture medium and glucose 6.4 ± 0.9%. Our results suggest that mechanisms for stone risk associated with fructose intake may lie in factors other than those affecting the major stone risk parameters in urine.}, }
@article {pmid20823364, year = {2010}, author = {Hurst, K}, title = {Primary hyperparathyroidism as a secondary cause of depression.}, journal = {Journal of the American Board of Family Medicine : JABFM}, volume = {23}, number = {5}, pages = {677-680}, doi = {10.3122/jabfm.2010.05.090199}, pmid = {20823364}, issn = {1558-7118}, mesh = {Adult ; Anti-Anxiety Agents/therapeutic use ; Antidepressive Agents, Second-Generation/therapeutic use ; Calcium/metabolism ; Depressive Disorder/drug therapy/*etiology/metabolism ; Female ; Humans ; Hyperparathyroidism, Primary/*psychology/surgery ; Kidney Calculi/metabolism ; Parathyroidectomy ; Suicidal Ideation ; Treatment Outcome ; }, abstract = {A 27-year-old woman was initially diagnosed and treated for depression with suicide ideation. Thirteen months later, kidney stones, an elevated parathyroid hormone, and elevated calcium levels led to a diagnosis of primary hyperparathyroidism. The patient was treated for hyperparathyroidism by resection of the superior right parathyroid gland. When the calcium levels were regulated, the patient's moods, concentration, and memory were back to baseline.}, }
@article {pmid20632168, year = {2010}, author = {Worcester, EM and Coe, FL}, title = {Evidence for altered renal tubule function in idiopathic calcium stone formers.}, journal = {Urological research}, volume = {38}, number = {4}, pages = {263-269}, pmid = {20632168}, issn = {1434-0879}, support = {P01 DK056788/DK/NIDDK NIH HHS/United States ; UL1 RR024999/RR/NCRR NIH HHS/United States ; NIDDK PO1 56788//PHS HHS/United States ; }, mesh = {Animals ; Calcium/metabolism ; Humans ; Kidney/physiopathology ; Kidney Calculi/*physiopathology ; Kidney Tubules, Proximal/*physiopathology ; Lithium/metabolism ; Phosphates/metabolism ; Rats ; }, abstract = {Patients who form calcium kidney stones often have metabolic disorders such as idiopathic hypercalciuria (IH) that reflect abnormalities in mineral handling in the kidney. Renal handling of calcium is altered by ingestion of nutrients such as carbohydrates, protein, and sodium, and patients with IH appear to be more sensitive to these stimuli. Studies using probes such as diuretics or lithium clearance have the ability to clarify which nephron segments are involved in the altered renal calcium transport with nutrient seen in IH. Studies in the genetic hypercalciuric rat demonstrate alterations in both proximal tubule and thick ascending limb calcium reabsorption. Similar studies in humans have begun to provide evidence about the corresponding abnormalities in stone formers with IH. A pattern of altered renal tubule transport in calcium stone formers is suggested by the frequency of such findings as decreased tubular maximal reabsorption of phosphate and abnormal urine acidification as well as hypercalciuria in such patients, not explained by monogenic transport abnormalities.}, }
@article {pmid20595678, year = {2010}, author = {Bindels, RJ}, title = {2009 Homer W. Smith Award: Minerals in motion: from new ion transporters to new concepts.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {21}, number = {8}, pages = {1263-1269}, doi = {10.1681/ASN.2010010001}, pmid = {20595678}, issn = {1533-3450}, mesh = {Animals ; Awards and Prizes ; Calcium/*metabolism ; Humans ; Ion Pumps/*metabolism ; Magnesium/*metabolism ; Mice ; Nephrons/metabolism ; }, abstract = {The kidneys play a critical role in maintaining the systemic balance of Mg(2+) and Ca(2+) cations. The reabsorptive capacity of these divalent cations adapt to changes in their plasma concentrations. Active reabsorption of Mg(2+) and Ca(2+) takes place in the distal convoluted and connecting tubules, respectively, and is initiated by cellular transport through selective transient receptor potential (TRP) channels located along the luminal membrane and modulated by hormonal stimuli. Recent characterization of underlying molecular defects in renal Mg(2+) handling illuminate complex transport processes in the kidney and their contribution to the overall mineral balance. Likewise, studies of Ca(2+) transport proteins in null mice disclose molecular mechanisms maintaining normal plasma Ca(2+) levels and the hypercalciuria-related adaptations important in the prevention of kidney stones. Current knowledge of Mg(2+) and Ca(2+) transport is summarized here as comprehensive cellular models of the distal nephron.}, }
@article {pmid20565975, year = {2010}, author = {Vandenbeuch, A and Tizzano, M and Anderson, CB and Stone, LM and Goldberg, D and Kinnamon, SC}, title = {Evidence for a role of glutamate as an efferent transmitter in taste buds.}, journal = {BMC neuroscience}, volume = {11}, number = {}, pages = {77}, pmid = {20565975}, issn = {1471-2202}, support = {P30 DC004657/DC/NIDCD NIH HHS/United States ; P30 DC04657/DC/NIDCD NIH HHS/United States ; R01 DC007495/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism ; Glutamic Acid/*metabolism/pharmacology ; Immunohistochemistry ; Mice ; Mice, Transgenic ; Neurons, Efferent/drug effects/*metabolism ; Receptors, Kainic Acid/*metabolism ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2X2 ; Reverse Transcriptase Polymerase Chain Reaction ; Taste Buds/drug effects/*metabolism ; Vesicular Glutamate Transport Protein 1/metabolism ; Vesicular Glutamate Transport Protein 2/metabolism ; }, abstract = {BACKGROUND: Glutamate has been proposed as a transmitter in the peripheral taste system in addition to its well-documented role as an umami taste stimulus. Evidence for a role as a transmitter includes the presence of ionotropic glutamate receptors in nerve fibers and taste cells, as well as the expression of the glutamate transporter GLAST in Type I taste cells. However, the source and targets of glutamate in lingual tissue are unclear. In the present study, we used molecular, physiological and immunohistochemical methods to investigate the origin of glutamate as well as the targeted receptors in taste buds.<br><br>RESULTS: Using molecular and immunohistochemical techniques, we show that the vesicular transporters for glutamate, VGLUT 1 and 2, but not VGLUT3, are expressed in the nerve fibers surrounding taste buds but likely not in taste cells themselves. Further, we show that P2X2, a specific marker for gustatory but not trigeminal fibers, co-localizes with VGLUT2, suggesting the VGLUT-expressing nerve fibers are of gustatory origin. Calcium imaging indicates that GAD67-GFP Type III taste cells, but not T1R3-GFP Type II cells, respond to glutamate at concentrations expected for a glutamate transmitter, and further, that these responses are partially blocked by NBQX, a specific AMPA/Kainate receptor antagonist. RT-PCR and immunohistochemistry confirm the presence of the Kainate receptor GluR7 in Type III taste cells, suggesting it may be a target of glutamate released from gustatory nerve fibers.<br><br>CONCLUSIONS: Taken together, the results suggest that glutamate may be released from gustatory nerve fibers using a vesicular mechanism to modulate Type III taste cells via GluR7.}, }
@article {pmid20553254, year = {2011}, author = {Xi, Q and Wang, S and Ye, Z and Liu, J and Yu, X and Zhu, Z and Su, S and Bai, J and Li, C}, title = {Adenovirus-delivered microRNA targeting the vitamin D receptor reduces intracellular Ca[2+] concentrations by regulating the expression of Ca[2+]-transport proteins in renal epithelial cells.}, journal = {BJU international}, volume = {107}, number = {8}, pages = {1314-1319}, doi = {10.1111/j.1464-410X.2010.09444.x}, pmid = {20553254}, issn = {1464-410X}, mesh = {Adenoviridae/genetics ; Animals ; Blotting, Western ; Calcium/*metabolism ; Calcium Channels/genetics/metabolism ; Cell Line ; Disease Models, Animal ; *Gene Expression Regulation ; Gene Targeting/*methods ; Hypercapnia/genetics/metabolism ; Intracellular Fluid/metabolism ; Kidney Cortex/metabolism/pathology ; MicroRNAs/*genetics ; Microscopy, Confocal ; Plasma Membrane Calcium-Transporting ATPases/biosynthesis/*genetics ; RNA, Viral/genetics ; Rats ; Receptors, Calcitriol/*genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Urothelium/*metabolism/pathology ; }, abstract = {UNLABELLED: What’s known on the subject? and What does the study add? Experimental data have shown that VDR overexpression in the duodenum and kidney cortex is a biological characteristic of genetic hypercalciuric stone-forming rats (GHS rat), and a link between idiopathic calcium stone formation and the microstatellite marker D12S339 (near the VDR locus) has been proven in humans. Our study shows that VDR can positively regulate the mRNA and protein expression of TRPV5, calbindin-D28k and PMCA1b in NRK cell lines. VDR knockdown results in a decrease in intracellular Ca[2+] concentration in NRK cell lines. The effect of the elevated VDR level in the kidney on hypercalciuria and the underlying mechanisms need to be further addressed.<br><br>OBJECTIVE: &#x2022; To determine the effects of vitamin D receptor (VDR) on hypercalciuria and the mechanisms underlying such effects.<br><br>MATERIALS AND METHODS: &#x2022; The adenovirus vector-delivered microRNA targeting rat VDR was constructed. We infected the normal rat kidney epithelial cell line NRK (Cellbank, China) with the adenovirus and then collected the cells at 0, 48, 72, 96, 120 h after infection. The mRNA and protein levels of VDR and VDR-dependent epithelial Ca2+ transport proteins were detected using real-time polymerase chain reaction and Western blot assays, respectively. &#x2022; Fluorescent Ca&#xb2;&#x207a; indicator Fluo-4 NW (Fluo-4 NW calcium assay kit, Molecular Probes, Invitrogen, USA) and laser scanning confocal microscope (Olympus, FV500-IX71, Japan) were used to detect the cytosolic free Ca&#xb2;&#x207a; concentration at different time points after infection.<br><br>RESULTS: &#x2022; The mRNA and protein level of VDR, transient receptor potential vanilloid receptor subtype 5 (TRPV5), calbindin-D28k and plasma membrane Ca&#xb2;&#x207a;-ATPase (PMCA1b) in infected NRK cells was significantly lower at 72 and 96 h after infection than that in control cells. &#x2022; There was no significant difference between the two groups in the mRNA and protein level of TRPV6 and the Na&#x207a;/Ca&#xb2;&#x207a;-exchanger (NCX1). &#x2022; Furthermore, VDR knockdown results in a decrease in intracellular Ca&#xb2;&#x207a; concentration ([Ca&#xb2;&#x207a;]i) in NRK cell lines.<br><br>CONCLUSIONS: &#x2022; Our study shows that VDR can positively regulate the mRNA and protein expression of TRPV5, calbindin-D28k and PMCA1b, but not of TRPV6 or NCX1, in NRK cell lines. VDR knockdown results in a decrease in [Ca&#xb2;&#x207a;]i in NRK cell lines. &#x2022; The effect of the elevated VDR level in the kidney on hypercalciuria and the mechanisms underlying need to be further addressed.}, }
@article {pmid20445282, year = {2010}, author = {Ohshima, H}, title = {[Secondary osteoporosis UPDATE. Bone loss due to bed rest and human space flight study].}, journal = {Clinical calcium}, volume = {20}, number = {5}, pages = {709-716}, pmid = {20445282}, issn = {0917-5857}, mesh = {*Bed Rest ; Bone Resorption ; Bone and Bones/metabolism ; Calcium/metabolism ; Humans ; Osteoporosis/*etiology/prevention &amp; control ; Risk ; *Space Flight ; Urolithiasis/etiology ; Weightlessness/*adverse effects ; }, abstract = {Bone loss and renal stone are significant medical concerns for bed rest subjects and space flight astronauts. Bone mineral loss occurs as secondary osteoporosis due to the unloading of weight bearing bones during bed rest and space flight. Increased bone resorption and bone metabolic uncoupling promote bone loss through the release of calcium from unloaded weight bearing bones. The rate of bone mineral loss during bed rest and space flight is about 1-2 percent per month, and recovery requires a period three or four times longer. To prevent bone loss caused by bed rest and space flight, a prophylactic countermeasure program based on scientific evidence should be developed.}, }
@article {pmid20431193, year = {2010}, author = {Brown, DM and Dickson, C and Duncan, P and Al-Attili, F and Stone, V}, title = {Interaction between nanoparticles and cytokine proteins: impact on protein and particle functionality.}, journal = {Nanotechnology}, volume = {21}, number = {21}, pages = {215104}, doi = {10.1088/0957-4484/21/21/215104}, pmid = {20431193}, issn = {1361-6528}, mesh = {Adsorption ; Analysis of Variance ; Calcium/chemistry/metabolism ; Cell Line ; HL-60 Cells ; Humans ; Intercellular Adhesion Molecule-1/chemistry/metabolism ; Interleukin-8/*chemistry/metabolism ; Nanoparticles/adverse effects/*chemistry ; Particle Size ; Soot/*chemistry/metabolism/pharmacokinetics ; Tumor Necrosis Factor-alpha/*chemistry/metabolism ; }, abstract = {There is increased use of nanomaterials in many applications due to their unique properties, such as their high surface area and surface reactivity. However, the potential health effects to workers, consumers and the environment exposed to nanoparticles (NPs) is unknown. The aim of this study was to investigate whether NPs which may enter the body could adsorb proteins and whether this interaction affects both the particle and the protein function. The cytokines IL-8 and TNF-alpha were adsorbed significantly more by 14 nm carbon black (CB) compared with a similar dose of 260 nm CB. Uncoated 14 nm CB particles produced a significant increase in intracellular calcium [Ca(2 +)](i) which was greater than a similar mass dose of 260 nm CB. The 260 nm CB produced an increase in ICAM-1 expression in A549 epithelial cells at a comparable dose of 14 nm CB, and after coating with TNF-alpha 260 nm CB produced significantly more ICAM-1 expression compared with control cells. TNF-alpha bound to 14 nm CB induced a level of ICAM-1 expression that was no greater than the control level, suggesting that the TNF-alpha activity may be inhibited. These results suggest that NP-protein interaction results both in a decrease in protein function and particle activity in the cellular assays tested and this is currently being investigated.}, }
@article {pmid20157217, year = {2010}, author = {Valle Díaz de la Guardia, F and Arrabal Martín, M and Arrabal Polo, MA and Quirosa Flores, S and Miján Ortiz, JL and Zuluaga Gómez, A}, title = {Renal lithiasis in patients with primary hyperparathyroidism. Evolution and treatment.}, journal = {Archivos espanoles de urologia}, volume = {63}, number = {1}, pages = {32-40}, pmid = {20157217}, issn = {1576-8260}, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Hyperparathyroidism, Primary/*complications/surgery ; Kidney Calculi/*complications ; Male ; Middle Aged ; Parathyroidectomy ; Retrospective Studies ; }, abstract = {OBJECTIVES: The relationship between hyperparathyroidism and lithiasis is quite known, so the study of parathyroid glands is especially mandatory in the face of relapses. Our objective is to analyze both primary hyperparathyroidism (PHPT) associated with renal lithiasis and the evolution of this condition after parathyroidectomy, as well as to study factors associated with the presence of lithiasis or bone pathology, and carry out a review on bibliography.<br><br>METHODS: We describe a retrospective study of a series comprising 287 cases of hyperparathyroidism: 237 of them were primary and the remaining 50, secondary. We have included: sex, age, evolution time and symptoms, diagnostic tests (biochemical, radiological and histological). Factors such as number of episodes prior to diagnosis and treatments were analyzed in patients with symptomatic lithiasis to know whether patients exhibited residual lithiasis after the management of calculi or whether patients underwent episodes after parathyroidectomy, or whether or not they were treated. Statistical analysis was carried out through SPSS 15.0 for Windows.<br><br>RESULTS: Forty five percent of the patients had suffered lithiasis episodes; 50%, osteopenia/osteoporosis; 23%, musculoskeletal pain; 23%, asthenia and/or depressive syndrome. In 13.5% of cases, diagnosis was supported by the presence of hypercalcemia; no other symptoms were detected. We have analyzed factors that favor or inhibit renal lithiasis formation and compared biochemical parameters from the group of primary hyperthyroidism that exhibited lithiasis (41 patients) with those patients who did not (49). We noted that lithiasis patients showed higher values of calcium, alkaline phosphatase, intact PTH, mean PTH, osteocalcin, and chlorine/phosphate, calciuria and phosphaturia indexes. Student's t test on two independent samples revealed significant statistical differences in calcium levels (p<0.05), intact PTH (<.05) and osteocalcin.<br><br>CONCLUSIONS: Primary hyperparathyroidism patients with lithiasis presented higher values of parathormone, alkaline phosphatase, osteocalcin, and Cl/P and calciuria indexes than lithiasis-free PHPT patients. These patients exhibit objective improvement of symptoms after parathyroidectomy, and rarely a recurrence of lithiasis, a factor that generally coincides with persistence of residual lithiasis.}, }
@article {pmid20144595, year = {2010}, author = {Liu, CC and Huang, SP and Tsai, LY and Wu, WJ and Juo, SH and Chou, YH and Huang, CH and Wu, MT}, title = {The impact of osteopontin promoter polymorphisms on the risk of calcium urolithiasis.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {411}, number = {9-10}, pages = {739-743}, doi = {10.1016/j.cca.2010.02.007}, pmid = {20144595}, issn = {1873-3492}, mesh = {Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; Calcium/*metabolism/urine ; Drinking Behavior ; Female ; Gene Frequency ; Genotype ; Heterozygote ; Homozygote ; Humans ; Male ; Middle Aged ; Osteopontin/*genetics/urine ; Polymorphism, Genetic/*genetics ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/*genetics ; Risk Factors ; Uric Acid/urine ; Urolithiasis/*genetics/urine ; Young Adult ; }, abstract = {BACKGROUND: Osteopontin (OPN) is an important modulator of urolithiasis formation. Three functional polymorphisms (-66T/G, -156delG/G, and -443T/G) on the promoter region of the OPN gene have been found to affect the gene expression and transcriptional activity. This study investigated the association of those three functional polymorphisms with the risk of calcium urolithiasis.<br><br>METHODS: A total of 249 cases diagnosed with calcium urolithiasis and 247 age- and sex-matched healthy controls were recruited from Kaohsiung Medical University Hospital between June, 2003 and February, 2007. All subjects completed a detailed questionnaire survey, and provided blood and urine samples for biochemical evaluations. Three single nucleotide polymorphisms were determined by using TaqMan 5' allelic discrimination assay.<br><br>RESULTS: In-156delG/G polymorphism, subjects who carried delG allele had a significantly higher risk of developing calcium urolithiasis than those with G allele (odds ratio=1.39; 95% confidence interval=1.02-1.90; P=0.037). In stone cases, subjects with delG/G and delG/delG genotypes also had significantly higher urinary ratio of calcium to OPN than those with G/G genotype (11.8+/-15.9 vs 7.08+/-5.26, P=0.021).<br><br>CONCLUSIONS: The -156 delG/G polymorphism of OPN gene could serve as a candidate genetic marker used to evaluate the risk of calcium urolithiasis.}, }
@article {pmid20139080, year = {2010}, author = {Aihara, T and Nakamura, M and Ueki, S and Hara, H and Miki, M and Arata, T}, title = {Switch action of troponin on muscle thin filament as revealed by spin labeling and pulsed EPR.}, journal = {The Journal of biological chemistry}, volume = {285}, number = {14}, pages = {10671-10677}, pmid = {20139080}, issn = {1083-351X}, mesh = {Animals ; Calcium/metabolism ; Chickens ; Cysteine/chemistry/genetics/metabolism ; *Electron Spin Resonance Spectroscopy ; Muscle Fibers, Skeletal/*chemistry/metabolism ; Muscle, Skeletal/*chemistry/metabolism ; Mutagenesis, Site-Directed ; Mutation/genetics ; Protein Conformation ; Rabbits ; *Spin Labels ; Troponin C/*chemistry/genetics/metabolism ; Troponin I/*chemistry/genetics/metabolism ; }, abstract = {We have used pulsed electron-electron double resonance (PELDOR) spectroscopy to measure the distance between spin labels at Cys(133) of the regulatory region of TnI (TnI133) and a native or genetically substituted cysteine of TnC (TnC44, TnC61, or TnC98). In the +Ca(2+) state, the TnC44-TnI133-T distance was 42 A, with a narrow distribution (half-width of 9 A), suggesting that the regulatory region binds the N-lobe of TnC. Distances for TnC61-TnI133 and TnC98-TnI133 were also determined to be 38 A (width of 12 A) and 22 A (width of 3.4 A), respectively. These values were all consistent with recently published crystal structure (Vinogradova, M. V., Stone, D. B., Malanina, G. G., Karatzaferi, C., Cooke, R., Mendelson, R. A., and Fletterick, R. J. (2005) Proc. Natl Acad. Sci. U.S.A. 102, 5038-5043). Similar distances were obtained with the same spin pairs on a reconstituted thin filament in the +Ca(2+) state. In the -Ca(2+) state, the distances displayed broad distributions, suggesting that the regulatory region of TnI was physically released from the N-lobe of TnC and consequently fluctuated over a variety of distances on a large scale (20-80 A). The interspin distance appeared longer on the filament than on troponin alone, consistent with the ability of the region to bind actin. These results support a concept that the regulatory region of TnI, as a molecular switch, binds to the exposed hydrophobic patch of TnC and traps the inhibitory region of TnI away from actin in Ca(2+) activation of muscle.}, }
@article {pmid20130196, year = {2010}, author = {Chouhan, AK and Zhang, J and Zinsmaier, KE and Macleod, GT}, title = {Presynaptic mitochondria in functionally different motor neurons exhibit similar affinities for Ca2+ but exert little influence as Ca2+ buffers at nerve firing rates in situ.}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, volume = {30}, number = {5}, pages = {1869-1881}, pmid = {20130196}, issn = {1529-2401}, support = {R01 NS061914/NS/NINDS NIH HHS/United States ; R01 NS061914-02/NS/NINDS NIH HHS/United States ; R21 NS055202/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Drosophila ; Larva ; Mitochondria/*metabolism/ultrastructure ; Motor Neurons/*metabolism/ultrastructure ; Presynaptic Terminals/*metabolism/ultrastructure ; Urinary Bladder Calculi/metabolism ; }, abstract = {Mitochondria accumulate within nerve terminals and support synaptic function, most notably through ATP production. They can also sequester Ca(2+) during nerve stimulation, but it is unknown whether this limits presynaptic Ca(2+) levels at physiological nerve firing rates. Similarly, it is unclear whether mitochondrial Ca(2+) sequestration differs between functionally different nerve terminals. We addressed these questions using a combination of synthetic and genetically encoded Ca(2+) indicators to examine cytosolic and mitochondrial Ca(2+) levels in presynaptic terminals of tonic (MN13-Ib) and phasic (MNSNb/d-Is) motor neurons in Drosophila, which, as we determined, fire during fictive locomotion at approximately 42 Hz and approximately 8 Hz, respectively. Mitochondrial Ca(2+) sequestration starts in both terminals at approximately 250 nM, exhibits a similar Ca(2+)-uptake affinity (approximately 410 nM), and does not require Ca(2+) release from the endoplasmic reticulum. Nonetheless, mitochondrial Ca(2+) uptake in type Is terminals is more responsive to low-frequency nerve stimulation and this is due to higher cytosolic Ca(2+) levels. Since type Ib terminals have a higher mitochondrial density than Is terminals, it seemed possible that greater mitochondrial Ca(2+) sequestration may be responsible for the lower cytosolic Ca(2+) levels in Ib terminals. However, genetic and pharmacological manipulations of mitochondrial Ca(2+) uptake did not significantly alter nerve-stimulated elevations in cytosolic Ca(2+) levels in either terminal type within physiologically relevant rates of stimulation. Our findings indicate that presynaptic mitochondria have a similar affinity for Ca(2+) in functionally different nerve terminals, but do not limit cytosolic Ca(2+) levels within the range of motor neuron firing rates in situ.}, }
@article {pmid21534441, year = {2010}, author = {Holt, K}, title = {Calcium imbalance, resulting disorders and the available prevention and treatment options.}, journal = {The Journal of practical nursing}, volume = {60}, number = {4}, pages = {13-21}, pmid = {21534441}, issn = {0022-3867}, mesh = {Calcium Metabolism Disorders/*therapy ; Calcium, Dietary ; Dietary Supplements ; Humans ; Hypercalcemia/diagnosis/physiopathology/therapy ; Hypocalcemia/diagnosis/physiopathology/therapy ; Kidney Calculi/physiopathology/prevention &amp; control ; Neoplasms/physiopathology/prevention &amp; control ; Nutrition Policy ; Osteoporosis/physiopathology/prevention &amp; control ; }, }
@article {pmid20007079, year = {2009}, author = {Luo, YL and Wang, YL and Li, NL and Zheng, TZ and Zhang, L and She, YL and Hu, SM}, title = {Actions of genistein on contractile response of smooth muscle isolated from guinea pig gallbladder.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {8}, number = {6}, pages = {614-619}, pmid = {20007079}, issn = {1499-3872}, mesh = {Animals ; Calcium/metabolism ; Dose-Response Relationship, Drug ; Female ; Gallbladder/*drug effects/metabolism ; Gallstones/chemically induced ; Genistein/adverse effects/*pharmacology ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction/*drug effects ; Muscle, Smooth/*drug effects/metabolism ; Phytoestrogens/adverse effects/*pharmacology ; Receptors, Histamine H2/drug effects/metabolism ; Sarcoplasmic Reticulum/drug effects/metabolism ; Signal Transduction/drug effects ; }, abstract = {BACKGROUND: Defective contractile motility of the gallbladder is an important factor for gallstone formation. Estrogen might increase the risk of gallstones and cholecystitis, and estradiol inhibits the contractile activity of isolated strips of guinea pig gallbladder. The potential risks associated with hormone replacement therapy (HRT) include symptomatic gallstones. Phytoestrogen have been used to treat menopause syndromes by replacing traditional estrogen. This experiment aimed to determine the effects of the phytoestrogen genistein on the contractile response of smooth muscle strips isolated from guinea pig gallbladder and its possible mechanism of action.<br><br>METHODS: Guinea pigs were sacrificed to remove the whole gallbladder. Two or three smooth muscle strips were cut longitudinally. Each strip was suspended in a tissue chamber containing Krebs solution. After 2 hours of equilibration, contractile response indexes were recorded. Different concentrations of genistein were added to the chamber and the contractile responses were measured. Each antagonist was added 2 minutes before genistein to study possible mechanisms. The effect of genistein on calcium-dependent contraction curves and biphasic contraction in calcium-free Krebs solution were measured.<br><br>RESULTS: Genistein decreased the resting tension dose-dependently, and reduced the mean contractile amplitude and frequency in gallbladder strips. Ranitidine partly inhibited the effect of genistein, but methylene blue, Nomega-nitro-L-arginine, and propranolol hydrochloride did not influence this action. Genistein had no significant effects on calcium-dependent contraction. Genistein reduced the first contraction induced by acetylcholine chloride, but did not affect the second contraction caused by CaCl2.<br><br>CONCLUSIONS: Genistein relaxed smooth muscle isolated from the gallbladder of guinea pigs and this might contribute to the formation of gallstones. The inhibitory action might be related to H2 receptors and the release of intracellular Ca2+ from sarcoplasmic reticulum. Replacing traditional estrogen with phytoestrogen to treat menopause syndromes may increase the risk of gallstone formation.}, }
@article {pmid19921167, year = {2010}, author = {Bibilash, BS and Vijay, A and Fazil Marickar, YM}, title = {Stone composition and metabolic status.}, journal = {Urological research}, volume = {38}, number = {3}, pages = {211-213}, pmid = {19921167}, issn = {1434-0879}, mesh = {Calcium Metabolism Disorders/*pathology/physiopathology ; Humans ; Kidney Calculi/*chemistry/*metabolism ; Risk Factors ; Urolithiasis/*pathology/physiopathology ; }, abstract = {This paper aims to study the correlation between biochemical risk factors of the stone former and the type of oxalate stone formed, namely calcium oxalate monohydrate (COM) and calcium oxalate dehydrate (COD). A retrospective study of 487 patients who had been attending the urinary stone clinic, Trivandrum during 1998-2007 was conducted. The stones retrieved from them were subjected to chemical analysis and FTIR spectrographic analysis. They were categorized into COM, COD, mixed COM+COD and others. Of 142 pure calcium oxalate stone patients, 87 were predominantly COM stone formers and 55 COD stone formers. Their metabolic status of 24 h urine and serum was assessed. The values of urine calcium, phosphorus, uric acid, magnesium, creatinine, oxalate, citric acid, sodium and potassium, serum values of calcium, phosphorus, uric acid, magnesium and creatinine and calculated values of creatinine clearance, tubular reabsorption of phosphate, calcium magnesium ratio and calcium oxalate ratio were recorded. Comparison was made between the COM stone group and the COD stone group. Patients forming COM stones had significantly higher mean values for urine calcium (P < 0.05), oxalate (P < 0.01) and magnesium (P < 0.05) levels and significantly lower level of urine calcium-oxalate ratio (P < 0.01) and urine calcium-magnesium ratio (P < 0.01) compared to COD stone forming patients. All other values failed to show significant difference. Patients, with higher urine oxalate, formed COM stones. Those with low magnesium (which is an inhibitor) formed more of COD stones. Urine calcium was high in both groups without showing significant variation from the mean. In patients with high calcium-oxalate and calcium-magnesium ratios, there is higher chance of forming a COD stone than COM. Identification of the crystallization pattern of the calcium stone will help in selecting treatment modalities.}, }
@article {pmid19846138, year = {2009}, author = {Rodgers, A and Lewandowski, S and Allie-Hamdulay, S and Pinnock, D and Baretta, G and Gambaro, G}, title = {Evening primrose oil supplementation increases citraturia and decreases other urinary risk factors for calcium oxalate urolithiasis.}, journal = {The Journal of urology}, volume = {182}, number = {6}, pages = {2957-2963}, doi = {10.1016/j.juro.2009.08.021}, pmid = {19846138}, issn = {1527-3792}, mesh = {Adolescent ; Adult ; *Black People ; *Calcium Oxalate/metabolism ; Citrates/*urine ; *Dietary Supplements ; Humans ; Linoleic Acids/*therapeutic use ; Male ; Oenothera biennis ; Plant Oils/*therapeutic use ; Risk Factors ; Urolithiasis/metabolism/*prevention &amp; control ; *White People ; Young Adult ; gamma-Linolenic Acid/*therapeutic use ; }, abstract = {PURPOSE: We investigated the effects of gamma-linolenic acid (an omega-6 polyunsaturated fatty acid) in the form of evening primrose oil on calcium oxalate urinary stone risk factors in 2 ethnic groups.<br><br>MATERIALS AND METHODS: Eight black and 8 white healthy male subjects ingested 1,000 mg evening primrose oil (Natrodale, Kuils River, South Africa) daily for 20 days while following a free diet. Arachidonic acid content was determined by a dietary questionnaire. On days 0, 10 and 20, and 4 days after protocol 24-hour urine samples were collected. Samples were analyzed using routine assays.<br><br>RESULTS: Citraturia increased significantly in each group. Urinary oxalate showed a tendency to decrease in black subjects. Calciuria and the Tiselius risk index decreased significantly in each group. Carryover effects were observed.<br><br>CONCLUSIONS: To our knowledge increased citraturia has not been previously reported for any essential fatty acid. We hypothesize that evening primrose oil inhibits lipogenesis, thereby decreasing citrate consumption. For the decrease in oxaluria we suggest that evening primrose oil alters membrane fatty acid composition, thereby inhibiting the modulation of protein kinases that lead to hyperoxaluria. In regard to decreased calciuria we suggest that evening primrose oil modulates delta-5 and/or delta-6-desaturase, thereby inhibiting the production of arachidonic acid and prostaglandin E2, which influence calciuria. The different response in the 2 groups with respect to oxaluria confirms previously reported differences in sensitivity toward supplemental ingestion. Data suggest that evening primrose oil supplementation should be investigated as a possible conservative treatment for calcium oxalate urolithiasis.}, }
@article {pmid19835652, year = {2009}, author = {Centeno, V and de Barboza, GD and Marchionatti, A and Rodríguez, V and Tolosa de Talamoni, N}, title = {Molecular mechanisms triggered by low-calcium diets.}, journal = {Nutrition research reviews}, volume = {22}, number = {2}, pages = {163-174}, doi = {10.1017/S0954422409990126}, pmid = {19835652}, issn = {1475-2700}, mesh = {Adipose Tissue/metabolism ; Animals ; Body Mass Index ; Bone and Bones/*metabolism ; Calcium/deficiency/metabolism ; Calcium, Dietary/administration &amp; dosage/*metabolism ; Diet ; Female ; Homeostasis ; Hormones/*metabolism ; Humans ; Hypertension/metabolism ; Immune System/*metabolism ; Insulin Resistance ; Intestinal Mucosa/*metabolism ; Kidney/*metabolism ; Lipid Metabolism ; Neoplasms/etiology ; Osteoporosis/metabolism ; Risk Factors ; Signal Transduction ; }, abstract = {Ca is not only essential for bone mineralisation, but also for regulation of extracellular and intracellular processes. When the Ca2+ intake is low, the efficiency of intestinal Ca2+ absorption and renal Ca2+ reabsorption is increased. This adaptive mechanism involves calcitriol enhancement via parathyroid hormone stimulation. Bone is also highly affected. Low Ca2+ intake is considered a risk factor for osteoporosis. Patients with renal lithiasis may be at higher risk of recurrence of stone formation when they have low Ca2+ intake. The role of dietary Ca2+ on the regulation of lipid metabolism and lipogenic genes in adipocytes might explain an inverse relationship between dairy intake and BMI. Dietary Ca2+ restriction produces impairment of the adipocyte apoptosis and dysregulation of glucocorticosteroid metabolism in the adipose tissue. An inverse relationship between hypertension and a low-Ca2+ diet has been described. Ca2+ facilitates weight loss and stimulates insulin sensitivity, which contributes to the decrease in the blood pressure. There is also evidence that dietary Ca2+ is associated with colorectal cancer. Dietary Ca2+ could alter the ratio of faecal bile acids, reducing the cytotoxicity of faecal water, or it could activate Ca2+-sensing receptors, triggering intracellular signalling pathways. Also it could bind luminal antigens, transporting them into mucosal mononuclear cells as a mechanism of immunosurveillance and promotion of tolerance. Data relative to nutritional Ca2+ and incidences of other human cancers are controversial. Health professionals should be aware of these nutritional complications and reinforce the dairy intakes to ensure the recommended Ca2+ requirements and prevent diseases.}, }
@article {pmid19779706, year = {2009}, author = {Marickar, YM}, title = {Calcium oxalate stone and gout.}, journal = {Urological research}, volume = {37}, number = {6}, pages = {345-347}, pmid = {19779706}, issn = {1434-0879}, mesh = {Calcium/metabolism ; Calcium Oxalate/*metabolism ; Case-Control Studies ; Gout/*metabolism ; Humans ; Phosphorus/metabolism ; Uric Acid/metabolism ; Urinary Calculi/*metabolism ; }, abstract = {Gout is well known to be produced by increased uric acid level in blood. The objective of this paper is to assess the relationship between gout and calcium oxalate stone formation in the humans. 48 patients with combination of gout and calcium oxalate stone problem were included. The biochemical values of this group were compared with 38 randomly selected uric acid stone patients with gout, 43 stone patients with gout alone, 100 calcium oxalate stone patients without gout and 30 controls, making a total of 259 patients. Various biochemical parameters, namely serum calcium, phosphorus and uric acid and 24-h urine calcium, phosphorus, uric acid, oxalate, citrate and magnesium were analysed. ANOVA and Duncan's multiple-range tests were performed to assess statistical significance of the variations. The promoters of stone formation, namely serum calcium (P < 0.05), phosphorus (P < 0.05) and uric acid (P < 0.05) and urine calcium (P < 0.05), uric acid (P < 0.05) and oxalate (P < 0.05) were significantly variable in the different groups. The inhibitor citrate (P < 0.05) was also significantly variable. Multiple-range test showed that the promoters, namely serum calcium (P < 0.05) and urine uric acid (P < 0.05) were in a significantly higher range in the gouty patients, gouty uric acid stone patients and gouty calcium oxalate stone patients compared to the non-gouty patients and controls. Urine oxalate (P < 0.0001) was in the highest range in the gouty calcium oxalate or gouty uric acid stones patients. The inhibitor urine citrate (P < 0.001) was significantly lower in the gouty, gouty uric acid and gouty calcium oxalate patients. Serum uric acid was highest in the non-stone gouty patients, followed by the gouty uric acid stone formers and gouty calcium oxalate stone patients. The high values of promoters, namely uric acid and calcium in the gouty stone patients indicate the tendency for urinary stone formation in the gouty stone patients. There is probably a correlation between gout and calcium oxalate urinary stone. We presume this mechanism is achieved through the uric acid metabolism. The findings point to the summation effect of metabolic changes in development of stone disease.}, }
@article {pmid19648675, year = {2009}, author = {Hu, G and Duan, L and Hu, X and Li, J and Yang, G and Tang, H}, title = {[Clinical trial on pancreatic duct stones caused by chronic pancreatitis].}, journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences}, volume = {34}, number = {7}, pages = {630-633}, pmid = {19648675}, issn = {1672-7347}, mesh = {Adult ; Aged ; Calcium/metabolism ; Calculi/*etiology/metabolism ; Female ; Humans ; Lactoferrin/metabolism ; Lithostathine/*metabolism ; Male ; Middle Aged ; Pancreatic Diseases/metabolism ; *Pancreatic Ducts ; Pancreatic Juice/*metabolism ; Pancreatitis, Chronic/*complications ; }, abstract = {OBJECTIVE: To determine the possible mechanism for chronic pancreatitis causing pancreatic duct stones.<br><br>METHODS: A total of 172 patients with chronic pancreatitis (n=67), pancreatic duct stones (n=62), and pancreatic injury (n=43), admitted to from August 2000 to October 2008, preoperatively diagnosed by endoscopic retrograde cholangiopancreatograpby(ERCP) or computed tomography(CT), and intraoperatively confirmed by exploration and biopsy, were divided into 3 groups. Pancreatic fluid was drawn to test the concentrations of pancreatic stone protein (PSP), lactoferrin (LF) and Ca2+.<br><br>RESULTS: The chronic pancreatitis (the CP group) presented hard consistency, shrinkage and nodular fibrosis of the pancreas; besides the above symptoms, the pancreatic duct stones (the PS group) presented dilatation of the pancreatic ductal system with various stones; pancreatic injury (the PI group) presented broken pancreas of different grades with fluid or blood. Compared with that of the PI group, PSP concentration of both the PS group and the CP group was elevated (P<0.05), and was more apparent in the CP group. Concentrations of LF and Ca2+ were also elevated (P<0.05), which were more obvious in the PS group.<br><br>CONCLUSION: Decreased concentrations of PSP and increased concentrations of LF and Ca2+ may play very important roles in chronic pancreatitis causing pancreatic duct stones.}, }
@article {pmid19626931, year = {2009}, author = {Stoermann Chopard, C and Jaeger, P}, title = {[Is kidney stone a bone disease?].}, journal = {Revue medicale suisse}, volume = {5}, number = {207}, pages = {1314-1317}, pmid = {19626931}, issn = {1660-9379}, mesh = {Adult ; *Bone Density ; Bone Diseases, Metabolic/complications/epidemiology/*metabolism/therapy ; Bone and Bones/metabolism ; Calcium/metabolism ; Calcium, Dietary/administration &amp; dosage ; Dietary Proteins ; Feeding Behavior ; Humans ; Hypercalciuria/metabolism ; Incidence ; Meta-Analysis as Topic ; Nephrolithiasis/epidemiology/etiology/*metabolism/therapy ; Osteoporosis/metabolism ; Risk Factors ; Switzerland/epidemiology ; Treatment Outcome ; }, abstract = {Idiopathic calcium stone formation affects 10% of the adult western population in a lifetime and is, consequently, a real public health problem in these countries. Abnormalities of bone metabolism with osteopenia have been found in patients with idiopathic hypercalciuria. The type of diet (high protein intake, calcium restriction) and some mediators (cytokines, calcitriol) are involved in the pathophysiology of bone alterations. The purpose of this article is to discuss the link between calcium nephrolithiasis and bone density, factors implicated in bone loss and how to treat this pathology.}, }
@article {pmid19561606, year = {2009}, author = {Thorleifsson, G and Holm, H and Edvardsson, V and Walters, GB and Styrkarsdottir, U and Gudbjartsson, DF and Sulem, P and Halldorsson, BV and de Vegt, F and d'Ancona, FC and den Heijer, M and Franzson, L and Christiansen, C and Alexandersen, P and Rafnar, T and Kristjansson, K and Sigurdsson, G and Kiemeney, LA and Bodvarsson, M and Indridason, OS and Palsson, R and Kong, A and Thorsteinsdottir, U and Stefansson, K}, title = {Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density.}, journal = {Nature genetics}, volume = {41}, number = {8}, pages = {926-930}, pmid = {19561606}, issn = {1546-1718}, mesh = {Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Bone Density/*genetics ; Calcium/metabolism ; Chromosomes, Human, Pair 21/genetics ; Claudins ; Female ; *Genetic Predisposition to Disease ; Humans ; Kidney Calculi/*genetics ; Membrane Proteins/*genetics ; Middle Aged ; Molecular Sequence Data ; Mutation/*genetics ; }, abstract = {Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the CLDN14 gene that associate with kidney stones (OR = 1.25 and P = 4.0 x 10(-12) for rs219780[C]). Approximately 62% of the general population is homozygous for rs219780[C] and is estimated to have 1.64 times greater risk of developing the disease compared to noncarriers. The CLDN14 gene is expressed in the kidney and regulates paracellular permeability at epithelial tight junctions. The same variants were also found to associate with reduced bone mineral density at the hip (P = 0.00039) and spine (P = 0.0077).}, }
@article {pmid19517103, year = {2009}, author = {Khan, SR and Canales, BK}, title = {Genetic basis of renal cellular dysfunction and the formation of kidney stones.}, journal = {Urological research}, volume = {37}, number = {4}, pages = {169-180}, pmid = {19517103}, issn = {1434-0879}, support = {R01 DK059765/DK/NIDDK NIH HHS/United States ; R01 DK065658/DK/NIDDK NIH HHS/United States ; R01DK065658/DK/NIDDK NIH HHS/United States ; R01DK59765/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism ; Cells/metabolism ; Citric Acid/metabolism ; Crystallization ; Humans ; Kidney/*metabolism/*physiopathology ; Kidney Calculi/*genetics/*metabolism ; Kidney Tubules/metabolism ; Mucoproteins/metabolism ; Oxalates/metabolism ; Uromodulin ; }, abstract = {Nephrolithiasis is a result of formation and retention of crystals within the kidneys. The driving force behind crystal formation is urinary supersaturation with respect to the stone-forming salts, which means that crystals form when the concentrations of participating ions are higher than the thermodynamic solubility for that salt. Levels of supersaturation are kept low and under control by proper functioning of a variety of cells including those that line the renal tubules. It is our hypothesis that crystal deposition, i.e., formation and retention in the kidneys, is a result of impaired cellular function, which may be intrinsic and inherent or triggered by external stimuli and challenges. Cellular impairment or dysfunction affects the supersaturation, by influencing the excretion of participating ions such as calcium, oxalate and citrate and causing hypercalciuria, hyperoxaluria or hypocitraturia. The production and excretion of macromolecular promoters and inhibitors of crystallization is also dependent upon proper functioning of the renal epithelial cells. Insufficient or ineffective crystallization modulators such as osteopontin, Tamm-Horsfall protein, bikunin, etc. are most likely produced by the impaired cells.}, }
@article {pmid19425219, year = {2009}, author = {Moriyama, MT and Suga, K and Miyazawa, K and Tanaka, T and Higashioka, M and Noda, K and Oka, M and Tanaka, M and Suzuki, K}, title = {Inhibitions of urinary oxidative stress and renal calcium level by an extract of Quercus salicina Blume/Quercus stenophylla Makino in a rat calcium oxalate urolithiasis model.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {16}, number = {4}, pages = {397-401}, doi = {10.1111/j.1442-2042.2009.02268.x}, pmid = {19425219}, issn = {1442-2042}, mesh = {Animals ; Calcium/analysis/*metabolism ; *Calcium Oxalate/metabolism ; Disease Models, Animal ; Kidney/chemistry/drug effects/*metabolism ; Male ; Oxidative Stress/*drug effects ; Plant Extracts/pharmacology/*therapeutic use ; *Quercus ; Rats ; Rats, Sprague-Dawley ; Urolithiasis/metabolism/*prevention &amp; control ; }, abstract = {OBJECTIVES: To clarify the mechanism of Urocalun, an extract of Quercus salicina Blume/Quercus stenophylla Makino (QS), in the treatment of urolithiasis.<br><br>METHODS: Rat calcium oxalate urolithiasis was induced by oral administration of ethylene glycol and the vitamin D3 analog alfa-calcidol for 14 days. QS extract was repeatedly given to rats. After the last administration, biochemistries in urine and plasma, renal calcium, and urinary malondialdehyde (an oxidative stress marker) were measured.<br><br>RESULTS: Ethylene glycol and alfa-calcidol treatment increased urinary malondialdehyde and renal calcium levels. This increase was significantly suppressed by the administration of QS extract, suggesting that the inhibition of renal calcium accumulation by QS extract is due to its antioxidative activity.<br><br>CONCLUSIONS: These findings suggest that the antioxidative activity of QS extract plays a role in the prevention of stone formation and recurrence in urolithiasis.}, }
@article {pmid19350280, year = {2009}, author = {Porowski, T and Konstantynowicz, J and Zoch-Zwierz, W and Kirejczyk, JK and Taranta-Janusz, K and Korzeniecka-Kozerska, A}, title = {Spontaneous urinary calcium oxalate crystallization in hypercalciuric children.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {24}, number = {9}, pages = {1705-1710}, pmid = {19350280}, issn = {1432-198X}, mesh = {Adolescent ; Calcium Oxalate/*urine ; Child ; Child, Preschool ; Comorbidity ; Crystallization ; Female ; Humans ; Hydrogen-Ion Concentration ; Hypercalciuria/diagnosis/epidemiology/*urine ; Kidney Calculi/diagnosis/epidemiology/*urine ; Male ; Poland/epidemiology ; Risk Factors ; Urinalysis ; }, abstract = {Idiopathic hypercalciuria is the most important predisposing risk factor for calcium oxalate (CaOx) renal stone formation. We assessed the associations between spontaneous CaOx crystallization based on the Bonn Risk Index (BRI), urinary pH, calciuria, oxaluria, and citraturia in 140 Caucasian patients with hypercalciuria, aged 4-17 years, and compared the findings with those in 210 normocalciuric controls. Of the 140 hypercalciuric patients, 58 had renal stones, and 82 had recurrent erythrocyturia, renal colic, or urinary obstructive symptoms-but without stones. Urinary ionized calcium ([Ca(2+)]) levels were measured using a selective electrode, while the onset of crystallization was determined using a photometer and titration with 40 mmol/L ammonium oxalate (Ox(2-)). The calculation of the BRI was based on the [Ca(2+)]:Ox(2-) ratio. The BRI values were 12-fold higher in hypercalciuric children than in healthy controls, but no differences were found in the BRI between subjects with urinary stones and those with urolithiasis-like symptoms. An increased BRI suggested an association with hypercalciuria, lower urinary pH, hypocitraturia, and hypooxaluria. These data indicate that hypercalciuria is an important factor associated with increased urinary CaOx crystallization, although the causal pathways need further investigation. Determination of the BRI in children with hypercalciuria may improve the risk assessment of kidney stones.}, }
@article {pmid19300989, year = {2009}, author = {Rodgers, A and Bungane, N and Allie-Hamdulay, S and Lewandowski, S and Webber, D}, title = {Calciuria, oxaluria and phosphaturia after ingestion of glucose, xylitol and sorbitol in two population groups with different stone-risk profiles.}, journal = {Urological research}, volume = {37}, number = {3}, pages = {121-125}, pmid = {19300989}, issn = {1434-0879}, mesh = {Adolescent ; Adult ; Black People ; Calcium/*urine ; Dietary Carbohydrates/*administration &amp; dosage/*adverse effects/metabolism ; Double-Blind Method ; Glucose/administration &amp; dosage/adverse effects/metabolism ; Humans ; Male ; Oxalates/*urine ; Phosphates/*urine ; Risk Factors ; Sorbitol/administration &amp; dosage/adverse effects/metabolism ; South Africa ; Urolithiasis/*etiology/metabolism/*urine ; White People ; Xylitol/administration &amp; dosage/adverse effects/metabolism ; Young Adult ; }, abstract = {The effects of glucose, sorbitol and xylitol ingestion on calciuria, oxaluria and phosphaturia in healthy black and white males on a standardized diet were investigated. After ingestion, they collected urine hourly for 3 h. Glucose decreased phosphaturia in blacks. Sorbitol decreased phosphaturia in both groups and increased oxaluria in whites. Xylitol increased oxaluria in blacks. Decreases in phosphaturia are attributed to penetration by phosphate into cells leading to decreases in phosphatemia and the renal filtered load. We suggest that this mechanism is more sensitive in blacks. We speculate that the increase in oxaluria after sorbitol ingestion occurs via its conversion to glyoxylate and that this pathway may be blocked in blacks. For the increase in oxaluria after xylitol ingestion, it is hypothesized that ketohexokinase and aldolase may be more active in blacks. Our results demonstrate, for the first time, a urinary effect due to sorbitol ingestion and an ethnic dependency of these and other effects.}, }
@article {pmid19299893, year = {2009}, author = {Taylor, JG and Bushinsky, DA}, title = {Calcium and phosphorus homeostasis.}, journal = {Blood purification}, volume = {27}, number = {4}, pages = {387-394}, doi = {10.1159/000209740}, pmid = {19299893}, issn = {1421-9735}, mesh = {Bone and Bones/metabolism ; Calcium/*metabolism ; *Homeostasis ; Humans ; Intestinal Mucosa/metabolism ; Kidney/metabolism ; Phosphorus/*metabolism ; }, abstract = {Calcium and phosphorus homeostasis relies on a complex, tightly regulated system involving many ions and hormones. The regulation of calcium and phosphorus is controlled by the actions of these ions and hormones on the intestine, kidneys and bone. Disturbances in the serum level of calcium and/or phosphorus can lead to significant pathology, including kidney stones and bone disease. In addition to parathyroid hormone and vitamin D, recently identified factors such as fibroblast growth factors and klotho play an important role in maintaining mineral ion homeostasis. The identification of subfamily V transient receptor potential cation channels (TRPV channels), Na/P(i) cotransporters, the vitamin D receptor and the calcium-sensing receptor have further advanced our understanding of this complex physiology. In this review we discuss the current understanding of the relationships between the ions, hormones, and transporters that maintain calcium and phosphorus homeostasis.}, }
@article {pmid19216637, year = {2009}, author = {Gómez-Núñez, JG and Alvarez, UM and Fernández, F and Aceves, JG and Loske, AM}, title = {Interaction of intracorporeal lithotripters with Proteus mirabilis inoculated inside artificial calcium and struvite stones.}, journal = {Journal of endourology}, volume = {23}, number = {3}, pages = {519-522}, doi = {10.1089/end.2008.0264}, pmid = {19216637}, issn = {1557-900X}, mesh = {Calcium/*metabolism ; Lithotripsy/*instrumentation ; Magnesium Compounds/*metabolism ; Microbial Viability ; Phosphates/*metabolism ; Proteus mirabilis/*cytology ; Struvite ; }, abstract = {BACKGROUND AND PURPOSE: Renal calculi may contain bacteria that can remain active inside the stone and produce bacteremia and/or endotoxemia after lithotripsy. Urinary tract infection associated with urinary stones represents high morbidity. The purpose of this research was to use novel artificial struvite stones inoculated with living bacteria and to study the effect of four different intracorporeal lithotripters on bacterial inactivation after in vitro lithotripsy.<br><br>MATERIALS AND METHODS: Two types of artificial kidney stone models (calcium sulphate and mixed struvite-calcium sulphate) were manufactured and infected with Proteus mirabilis. Stones were fractured using either electrohydraulic, laser, ultrasonic, or pneumatic lithotripters. Bacterial viability was determined before and after the lithotripsy.<br><br>RESULTS: Bacterial inactivation was not affected by the stone matrix; ie, calcium or struvite. The four tested lithotripters were almost equally efficient at reducing the viability of P mirabilis in both the low and the high energy setting.<br><br>CONCLUSIONS: We were able to obtain novel artificial struvite stones infected with bacteria. Intracorporeal lithotripters are efficient at reducing the viability of P mirabilis in vitro. Tested stone materials play a minor role regarding inactivation. Whether the bactericidal effect reported is desirable or not is still to be answered, because the presence of endotoxin from cell lysis may increase the risk of urosepsis.}, }
@article {pmid19160242, year = {2009}, author = {Escribano, J and Balaguer, A and Pagone, F and Feliu, A and Roqué I Figuls, M}, title = {Pharmacological interventions for preventing complications in idiopathic hypercalciuria.}, journal = {The Cochrane database of systematic reviews}, volume = {2009}, number = {1}, pages = {CD004754}, pmid = {19160242}, issn = {1469-493X}, mesh = {Adult ; Diuretics/*therapeutic use ; Drinking ; Humans ; Hypercalciuria/complications/diet therapy/*drug therapy ; Kidney Calculi/etiology/*prevention &amp; control ; Randomized Controlled Trials as Topic ; Thiazides/*therapeutic use ; Water/administration &amp; dosage ; }, abstract = {BACKGROUND: Idiopathic hypercalciuria is an inherited metabolic abnormality characterised by excessive amounts of calcium excreted into the urine in patients with normal serum levels of calcium. The morbidity of hypercalciuria is related to kidney stone disease and bone demineralization. In children, hypercalciuria can cause recurrent haematuria, frequency-dysuria syndrome, urinary tract infection and abdominal and lumbar pain. Several pharmacological treatments have been described that can decrease the levels of urinary calcium or its index of urinary crystallization.<br><br>OBJECTIVES: To assess the benefits and harms of pharmacological interventions for preventing complications and decreasing urological symptoms in patients with idiopathic hypercalciuria.<br><br>SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), handsearched relevant conference proceedings and reference lists of articles.<br><br>SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTS that compared any pharmacological intervention for preventing complications in idiopathic hypercalciuria, with placebo, other pharmacological intervention or a different administration mode or dose of the same treatment given for a minimum duration of four months and had a follow-up period of at least six months.<br><br>DATA COLLECTION AND ANALYSIS: Four authors assessed the studies for inclusion and extracted the data. Disagreements were resolved through discussion. Results were expressed as risk ratios (RR) with 95% confidence intervals (CI) or mean difference (MD).<br><br>MAIN RESULTS: Five studies (316 adult patients) were included. Four compared thiazides with standard treatment (periodic clinical follow-up and increased water intake) or specific dietary recommendations and one analysed the effect of thiazide plus a neutral potassium salt. There was a significant decrease in the number of new stone recurrences in those treated with thiazides (RR 1.61, 95% CI 1.33 to 1.96), although the follow-up periods varied. The stone formation rate also showed a statistically significant decrease in the patients treated with diuretics (MD -0.18, 95% CI -0.30 to -0.06). Thiazides plus potassium salts significantly decreased calciuria and vitamin D levels.<br><br>AUTHORS' CONCLUSIONS: There is some evidence that in patients with idiopathic hypercalciuria and recurrent stones, the addition of thiazides to a normal or modified diet for short to long periods (five months to three years) reduced the number of stone recurrences and decreased the stone formation rate. Thiazides and neutral potassium phosphate decreased calciuria in symptomatic patients with idiopathic hypercalciuria. There were no studies investigating the effect of pharmacological treatment on other clinical complications or asymptomatic idiopathic hypercalciuria.}, }
@article {pmid19134407, year = {2008}, author = {Yang, Y and Qiao, JH and An, JH and Zhang, Y and Yu, T and Jia, B and Ma, ZS}, title = {[Detection of SLC34A2 in patients with pulmonary alveolar microlithiasis and the effect of SLC34A2 on transportation of calcium and phosphate in human alveolar epithelial cells].}, journal = {Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases}, volume = {31}, number = {12}, pages = {908-911}, pmid = {19134407}, issn = {1001-0939}, mesh = {Alveolar Epithelial Cells/cytology ; Calcium/*metabolism ; Calculi/metabolism/*pathology ; Cell Line ; Extracellular Fluid/metabolism ; Humans ; Phosphates/*metabolism ; Pulmonary Alveoli/cytology/*metabolism/*pathology ; RNA, Messenger/genetics ; Sodium-Phosphate Cotransporter Proteins, Type IIb/*genetics ; Transfection ; }, abstract = {OBJECTIVE: To detect the mutation of SLC34A2 in patients with pulmonary alveolar microlithiasis and to study the effect of SLC34A2 on transportation of calcium and phosphate in human alveolar epithelial cell (A549) cells.<br><br>METHODS: The gene SLC34A2 was detected by segmentation-PCR and gene sequencing. RNA was obtained by Trizol from fresh lung tissues and the target gene was acquired by RT-PCR. Eukaryotic expression of recombinant pcDNA3.1(+)-SLC34A2 was constructed and SLC34A2 was transfected to A549 cells by liposome. The expression of SLC34A2 mRNA was detected by RT-PCR, and the content of calcium and phosphate of the extracellular fluid was measured by commercial kits. The cell experiments consisted of 3 groups including a control group (5 x 10(5)/well, one well), a blank group (5 x 10(5)/well, one well), a transfection group (5 x 10(5)/well, four wells). Every experiment was repeated 6 times.<br><br>RESULTS: No mutation was found in patients with pulmonary alveolar microlithiasis. SLC34A2 cDNA was successfully amplified and the eukaryotic expression recombinant pcDNA3.1(+)-SLC34A2 was successfully constructed. The amount of SLC34A2 mRNA of the transfected cells was significantly higher (2.48 +/- 0.45), compared to the control cells (0.55 +/- 0.07) and the blank cells (0.60 +/- 0.06), q = 16.25, 15.78, all P < 0.01. The content of calcium and phosphate in the supernatant of the transfected cells was lower [(0.110 +/- 0.016) mmol/L, (3.8 +/- 0.4) mmol/L], compared with the control [(0.254 +/- 0.047) mmol/L, (7.3 +/- 0.8) mmol/L] and the blank (0.262 +/- 0.041) mmol/L, (7.1 +/- 0.4) mmol/L], q = 8.657 - 13.892, all P < 0.01.<br><br>CONCLUSIONS: In human lung alveolar epithelial cells, the content of calcium and phosphate in cell supernatant decreased with increased amount of SLC34A2 mRNA. Mutation of SLC34A2 may not be at the DNA level.}, }
@article {pmid19122701, year = {2008}, author = {Singh, VK and Singh, V and Rai, AK and Thakur, SN and Rai, PK and Singh, JP}, title = {Quantitative analysis of gallstones using laser-induced breakdown spectroscopy.}, journal = {Applied optics}, volume = {47}, number = {31}, pages = {G38-47}, doi = {10.1364/ao.47.000g38}, pmid = {19122701}, issn = {1539-4522}, mesh = {Adult ; Calcium/metabolism ; Calibration ; Equipment Design ; Gallstones/metabolism ; Humans ; *Lasers ; Male ; Metals/chemistry ; Middle Aged ; Spectrophotometry/methods ; Spectrophotometry, Atomic/methods ; Spectrum Analysis/*methods ; Thermodynamics ; Time Factors ; }, abstract = {The utility of laser-induced breakdown spectroscopy (LIBS) for categorizing different types of gallbladder stone has been demonstrated by analyzing their major and minor constituents. LIBS spectra of three types of gallstone have been recorded in the 200-900 nm spectral region. Calcium is found to be the major element in all types of gallbladder stone. The spectrophotometric method has been used to classify the stones. A calibration-free LIBS method has been used for the quantitative analysis of metal elements, and the results have been compared with those obtained from inductively coupled plasma atomic emission spectroscopy (ICP-AES) measurements. The single-shot LIBS spectra from different points on the cross section (in steps of 0.5 mm from one end to the other) of gallstones have also been recorded to study the variation of constituents from the center to the surface. The presence of different metal elements and their possible role in gallstone formation is discussed.}, }
@article {pmid19066877, year = {2009}, author = {Grases, F and Prieto, RM and Gomila, I and Sanchis, P and Costa-Bauzá, A}, title = {Phytotherapy and renal stones: the role of antioxidants. A pilot study in Wistar rats.}, journal = {Urological research}, volume = {37}, number = {1}, pages = {35-40}, pmid = {19066877}, issn = {1434-0879}, mesh = {Animals ; Antioxidants/*pharmacology ; Calcium/metabolism ; Catechin/pharmacology ; Crystallization ; Ethylene Glycol/toxicity ; Kidney Calculi/chemically induced/*drug therapy/metabolism/pathology ; Male ; *Phytotherapy ; Pilot Projects ; Plant Extracts/pharmacology ; Rats ; Rats, Wistar ; }, abstract = {Since ancient times, various herbal preparations have been used in renal lithiasis therapy, but conclusive scientific data on their therapeutic effects and efficacy are not available. To address this issue, the present study evaluated the antilithiasic activity of a traditional Mallorcan herbal preparation, and compared its effects with those of the antioxidant flavonoids, catechin and epicatechin. Thirty-six male Wistar rats were assigned randomly to four groups (n = 9): a control group, a catechin (CAT) treatment group, an epicatechin (EPI) treatment group, and a group treated with a folk herbal extract (FHE). After 16 days of treatment, calcium oxalate lithiasis was induced in the rats using ethylene glycol. After 8 days (treatment + ethylene glycol), 24-h rat urine was collected, the animals were sacrificed and their kidneys were removed for histological and chemical analysis. The calcium concentration in kidney tissue was significantly lower in the CAT-treated (2.4 +/- 0.3 mg/g), EPI-treated (1.8 +/- 0.3 mg/g) and FHE-treated (2.1 +/- 0.3 mg/g) groups, than in the control group (5.4 +/- 1.4 mg/g). Examination of paraffin-embedded kidney sections showed that control group rats had the greatest amount of calcification. There were no significant differences between control and treated groups with respect to urinary calcium, magnesium, oxalate and citrate concentrations. These results demonstrate the ability of herbal preparations and antioxidants to prevent the development of papillary and intratubular calcification in the kidney.}, }
@article {pmid19029225, year = {2009}, author = {Corbetta, S and Eller-Vainicher, C and Frigerio, M and Valaperta, R and Costa, E and Vicentini, L and Baccarelli, A and Beck-Peccoz, P and Spada, A}, title = {Analysis of the 206M polymorphic variant of the SLC26A6 gene encoding a Cl- oxalate transporter in patients with primary hyperparathyroidism.}, journal = {European journal of endocrinology}, volume = {160}, number = {2}, pages = {283-288}, doi = {10.1530/EJE-08-0623}, pmid = {19029225}, issn = {1479-683X}, mesh = {Aged ; Chlorides/metabolism ; Female ; Gene Frequency ; Genetic Predisposition to Disease/epidemiology ; Genotype ; Humans ; Hyperparathyroidism, Primary/*epidemiology/*genetics ; Incidence ; Italy/epidemiology ; Kidney Calculi/*epidemiology/*genetics ; Male ; Membrane Transport Proteins/*genetics/metabolism ; Middle Aged ; Oxalates/metabolism ; Polymorphism, Genetic ; Prevalence ; Risk Factors ; Sulfate Transporters ; }, abstract = {OBJECTIVE: Primary hyperparathyroidism (PHPT) is often complicated by kidney stones. Hypercalciuria and urine oxalate excretion are considered risk factors for urolithiasis in PHPT as well as in idiopathic stone-formers. Recently, the anion-exchanger SLC26A6 has been involved in the oxalate metabolism.<br><br>DESIGN AND METHODS: We tested the hypothesis that the 206M polymorphic variant of SLC26A6 gene might contribute to the risk of kidney stones in PHPT. DNA samples from 145 PHPT patients and 129 age- and sex-matched healthy subjects were genotyped.<br><br>RESULTS: The homozygous 206V genotype was the most frequent both in PHPT patients and controls (79.3 and 74.4%), while heterozygosity for the 206M allele was detected in 20.0 and 23.3% respectively. The homozygous 206M genotype was extremely rare, occurring in 0.7 and 2.3% of PHPT and healthy subjects respectively. In the PHPT cohort, the prevalence of urolithiasis did not differ between the V/V and V/M+M/M groups and urine oxalate excretions did not correlate with the genotype. Considering the subset of PHPT stone formers (n=74), calciuria was lower in V/M+M/M patients with respect to V/V stone-formers (4.40+/-1.88 vs 5.92+/-2.62 mg/kg per 24 h; mean+/-s.d., P=0.034). Finally, the SLC26A6 206M alleles were significantly related to the presence of hypertension (73.3 vs 47.8%), showing an OR of 4.8.<br><br>CONCLUSIONS: Though the SLC26A6 206M polymorphism did not correlate with kidney stone development in PHPT patients, PHPT stone-formers harbouring the M allele had a lower hypercalciuria. This observation and the high prevalence of hypertension associated with the 206M polymorphism need further investigation.}, }
@article {pmid18924500, year = {2008}, author = {Kamińska, A and Sołtyski, J and Roszkowska-Blaim, M}, title = {[Usefulness of Pak's test in Stapleton's modification in diagnosis of hypercalciuria in children].}, journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego}, volume = {24 Suppl 4}, number = {}, pages = {38-40}, pmid = {18924500}, issn = {1426-9686}, mesh = {Adolescent ; Child ; Child, Preschool ; *Diagnostic Techniques, Urological ; Female ; Humans ; Hypercalcemia/classification/*diagnosis/*urine ; Male ; }, abstract = {UNLABELLED: Recognition of the type of hypercalciuria in children in Pak's test in Stapleton's modification was performed. 26 children with hypercalciuria was enrolled to the study. 15/26 had positive family history. In all Pak's test in Stapleton's modification was done, blond tests of renal function (urea, creatinine), calcium-phosphate balance (Ca, P, ALP, PTH, Vit D3 metabolites) and in 24 hr urine collection: promoters and inhibitors of crystallization, 24 hr urine pH measurement was performed.<br><br>RESULTS: In 18 children--absorptive hipercalciuria: type II, in 1--type I, renal in 4; complex mechanism in 3, hypocitraturia was recognized in 4. Normalization of calciuria was obtained in 16 out of 26. In 3 others new formation of kidney stones was observed.<br><br>CONCLUSIONS: Performation of Pak's test in Stapleton's modification allows to establish a type of hypercalciuria in children and recognize a pathomechanism of disease.}, }
@article {pmid18923545, year = {2008}, author = {Musse, AA and Polverini, E and Raijmakers, R and Harauz, G}, title = {Kinetics of human peptidylarginine deiminase 2 (hPAD2)--reduction of Ca2+ dependence by phospholipids and assessment of proposed inhibition by paclitaxel side chains.}, journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire}, volume = {86}, number = {5}, pages = {437-447}, doi = {10.1139/o08-124}, pmid = {18923545}, issn = {0829-8211}, mesh = {Amino Acid Sequence ; *Antineoplastic Agents, Phytogenic/chemistry/metabolism ; Calcium/*metabolism ; Catalytic Domain ; Humans ; Hydrolases/chemistry/genetics/*metabolism ; Isoenzymes/chemistry/genetics/*metabolism ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Molecular Structure ; Multiple Sclerosis/enzymology ; *Paclitaxel/chemistry/metabolism ; Phospholipids/*metabolism ; Protein Conformation ; Protein-Arginine Deiminase Type 2 ; Protein-Arginine Deiminase Type 4 ; Protein-Arginine Deiminases ; Sequence Alignment ; }, abstract = {Multiple sclerosis is a complex human neurodegenerative disease, characterized by the active destruction of the insulating myelin sheath around the axons in the central nervous system. The physical deterioration of myelin is mediated by hyperdeimination of myelin basic and other proteins, catalysed by the Ca2+ -dependent enzyme peptidylarginine deiminase 2 (PAD2). Thus, inhibition of PAD2 may be of value in treatment of this disease. Here, we have first characterized the in vitro kinetic properties of the human peptidylarginine deiminase isoform 2 (hPAD2). Phosphatidylserine and phosphatidylcholine reduced its Ca2+ dependence by almost twofold. Second, we have explored the putative inhibitory action of the methyl ester side chain of paclitaxel (TSME), which shares structural features with a synthetic PAD substrate, viz., the benzoyl-L-arginine ethyl ester (BAEE). Using the known crystallographic structure of the homologous enzyme hPAD4 and in silico molecular docking, we have shown that TSME interacted strongly with the catalytic site, albeit with a 100-fold lower affinity than BAEE. Despite paclitaxel having previously been shown to inhibit hPAD2 in vitro, the side chain of paclitaxel alone did not inhibit this enzyme's activity.}, }
@article {pmid18758029, year = {2008}, author = {Ohshima, H and Mukai, C}, title = {[Bone metabolism in human space flight and bed rest study].}, journal = {Clinical calcium}, volume = {18}, number = {9}, pages = {1245-1253}, pmid = {18758029}, issn = {0917-5857}, mesh = {Amino Acids/urine ; Atrophy ; Bed Rest/*adverse effects ; Biomarkers/urine ; *Bone Density ; Bone Density Conservation Agents/administration &amp; dosage ; Bone and Bones/*metabolism ; Calcium/metabolism ; Collagen Type I/urine ; Humans ; Muscle, Skeletal/pathology ; Osteoporosis/*etiology/prevention &amp; control ; Peptides/urine ; *Space Flight ; Urinary Calculi/etiology ; Weightlessness/*adverse effects ; }, abstract = {Japanese Experiment Module "KIBO" is Japan's first manned space facility and will be operated as part of the international space station (ISS) . KIBO operations will be monitored and controlled from Tsukuba Space Center. In Japan, after the KIBO element components are fully assembled and activated aboard the ISS, Japanese astronauts will stay on the ISS for three or more months, and full-scale experiment operations will begin. Bone loss and renal stone are significant medical concerns for long duration human space flight. This paper will summarize the results of bone loss, calcium balance obtained from the American and Russian space programs, and ground-base analog bedrest studies. Current in-flight training program, nutritional recommendations and future countermeasure plans for station astronauts are also described.}, }
@article {pmid18715937, year = {2008}, author = {Worcester, EM and Coe, FL and Evan, AP and Bergsland, KJ and Parks, JH and Willis, LR and Clark, DL and Gillen, DL}, title = {Evidence for increased postprandial distal nephron calcium delivery in hypercalciuric stone-forming patients.}, journal = {American journal of physiology. Renal physiology}, volume = {295}, number = {5}, pages = {F1286-94}, pmid = {18715937}, issn = {1931-857X}, support = {P01 DK056788/DK/NIDDK NIH HHS/United States ; DK-P01-56788/DK/NIDDK NIH HHS/United States ; M01-00055//PHS HHS/United States ; }, mesh = {Adult ; Blood Pressure/physiology ; Calcium/blood/*metabolism/urine ; Creatinine/blood/metabolism/urine ; Female ; Humans ; Hypercalciuria/*metabolism/physiopathology ; Kidney Calculi/*metabolism/physiopathology ; Kidney Tubules, Proximal/metabolism/physiopathology ; Lithium/blood/metabolism/urine ; Male ; Middle Aged ; Nephrons/*metabolism/physiopathology ; Postprandial Period/*physiology ; Potassium/blood/metabolism/urine ; Sodium/blood/metabolism/urine ; }, abstract = {A main mechanism of idiopathic hypercalciuria (IH) in calcium stone-forming patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption that cannot be explained by selective reduction of serum parathyroid hormone levels; the nephron site(s) responsible are not as yet defined. Using fourteen 1-h measurements of the clearances of sodium, calcium, and endogenous lithium during a three-meal day in the University of Chicago General Clinical Research Center, we found reduced postprandial proximal tubule reabsorption of sodium and calcium in IHSF vs. normal subjects. The increased distal sodium delivery is matched by increased distal reabsorption so that urine sodium excretions do not differ, but distal calcium reabsorption does not increase enough to match increased calcium delivery, so hypercalciuria results. In fact, urine calcium excretion and overall renal fractional calcium reabsorption both are high in IHSF vs. normal when adjusted for distal calcium delivery, strongly suggesting a distal as well as proximal reduction of calcium reabsorption. The combination of reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new finding and indicates that IH involves a complex, presumably genetic, variation of nephron function. The increased calcium delivery into the later nephron may play a role in stone formation via deposition of papillary interstitial apatite plaque.}, }
@article {pmid18664357, year = {2008}, author = {Zhang, JZ and Zhang, XL and Liang, XQ and Gu, HG and Zhu, PT}, title = {[Effects of different Chinese herbal medicines on biochemical parameters in guinea-pig with pigment gallstones].}, journal = {Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine}, volume = {6}, number = {8}, pages = {856-859}, doi = {10.3736/jcim20080816}, pmid = {18664357}, issn = {1672-1977}, mesh = {Animals ; Bile Pigments/*metabolism ; Calcium/metabolism ; Cholagogues and Choleretics/therapeutic use ; Drugs, Chinese Herbal/*therapeutic use ; Gallstones/chemically induced/*chemistry/*drug therapy ; Guinea Pigs ; Lincomycin ; Male ; *Phytotherapy ; Random Allocation ; }, abstract = {OBJECTIVE: To observe the effects of Qingdan Capsule (QDC) and Yanggan Lidan Granule (YGLDG), two kinds of compound traditional Chinese herbal medicines, on biochemical parameters in guinea-pigs with pigment gallstones.<br><br>METHODS: An animal model of pigment gallstones was established in male guinea-pigs by hypodermic injection of lincomycin. The guinea-pigs were randomly divided into blank control group, untreated group, QDC group and YGLDG group. There were 8 guinea-pigs in each group. After ten-day treatment, animals were sacrificed and sampled to calculate the rate of stone formation, total bilirubin (TB), unconjugated bilirubin (UCB) and Ca2+ density in bile of the four groups.<br><br>RESULTS: In comparison with the untreated group, the rates of stone formation in the QDC and YGLDG groups were significantly decreased (P<0.01). TBIL, UCB and Ca2+ content of bile in both QDC and YGLD groups was also significantly decreased (P<0.05, P<0.01).<br><br>CONCLUSION: QDC and YGLD have good effects on biochemical changes of animal model of pigment gallstone in reversing the lithogenesity of bile by reducing the content of TB, UCB and Ca2+, hence resulting in clinical treatment and prevention of pigment gallstone disease.}, }
@article {pmid18596722, year = {2008}, author = {de Groot, T and Bindels, RJ and Hoenderop, JG}, title = {TRPV5: an ingeniously controlled calcium channel.}, journal = {Kidney international}, volume = {74}, number = {10}, pages = {1241-1246}, doi = {10.1038/ki.2008.320}, pmid = {18596722}, issn = {1523-1755}, mesh = {Calcium/metabolism ; Calcium Channels ; Hemostasis ; Humans ; Kidney/metabolism/physiology ; TRPV Cation Channels/*physiology ; }, abstract = {Body Ca(2+) homeostasis is tightly controlled and slight disturbances in renal Ca(2+) reabsorption can lead to excessive urine Ca(2+) excretion and promote kidney stone formation. The epithelial Ca(2+) channel TRPV5 constitutes the rate-limiting step of active Ca(2+) reabsorption in the kidney. Elucidation of the molecular pathways controlling TRPV5 function provides important information for our understanding of renal Ca(2+) handling, since active Ca(2+) reabsorption fine-tunes the final amount of Ca(2+) excreted into the urine. Over the last years, the molecular regulation of TRPV5 has been dismantled in detail. Various calciotropic hormones, known to alter renal Ca(2+) reabsorption, affect the expression of TRPV5. Others stimulate the trafficking of TRPV5 to the plasma membrane, while a number of associated proteins and ions control channel activity at the plasma membrane. Dynamic cell surface presence of TRPV5 is largely mediated by endosomal recycling processes allowing internalized channels to reappear at the plasma membrane. We present recently identified factors shown to modulate TRPV5 activity by diverse mechanisms to ultimately control renal Ca(2+) handling. The selected factors include klotho, tissue kallikrein, pH, Ca(2+), Mg(2+), PIP(2) and WNK4. This review covers the distinctive properties and regulation of the highly Ca(2+)-selective TRPV5 channel and highlights the implications for our understanding of the process of Ca(2+) reabsorption.}, }
@article {pmid18487315, year = {2008}, author = {Stones, R and Natali, A and Billeter, R and Harrison, S and White, E}, title = {Voluntary exercise-induced changes in beta2-adrenoceptor signalling in rat ventricular myocytes.}, journal = {Experimental physiology}, volume = {93}, number = {9}, pages = {1065-1075}, pmid = {18487315}, issn = {0958-0670}, support = {//British Heart Foundation/United Kingdom ; }, mesh = {Animals ; Calcium/metabolism ; Cardiomegaly/metabolism ; Cardiotonic Agents/pharmacology ; Female ; Isoproterenol/pharmacology ; Myocytes, Cardiac/cytology/drug effects/*metabolism ; Physical Conditioning, Animal/*physiology ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-1/metabolism ; Receptors, Adrenergic, beta-2/genetics/*metabolism ; Signal Transduction/*physiology ; }, abstract = {Regular exercise is beneficial to cardiovascular health. We tested whether mild voluntary exercise training modifies key myocardial parameters [ventricular mass, intracellular calcium ([Ca2+]i) handling and the response to beta-adrenoceptor (beta-AR) stimulation] in a manner distinct from that reported for beneficial, intensive training and pathological hypertrophic stimuli. Female rats performed voluntary wheel-running exercise for 6-7 weeks. The mRNA expression of target proteins was measured in left ventricular tissue using real-time reverse transcriptase-polymerase chain reaction. Simultaneous measurement of cell shortening and [Ca2+]i transients were made in single left ventricular myocytes and the inotropic response to beta1- and beta2-AR stimulation was measured. Voluntary exercise training resulted in cardiac hypertrophy, the heart weight to body weight ratio being significantly greater in trained compared with sedentary animals. However, voluntary exercise caused no significant alteration in the size or time course of myocyte shortening and [Ca2+]i transients or in the mRNA levels of key proteins that regulate Ca2+ handling. The positive inotropic response to beta1-AR stimulation and the level of beta1-AR mRNA were unaltered by voluntary exercise but both mRNA levels and inotropic response to beta2-AR stimulation were significantly reduced in trained animals. The beta2-AR inotropic response was restored by exposure to pertussis toxin. We propose that in contrast to pathological stimuli and to beneficial, intense exercise training, modulation of Ca2+ handling is not a major adaptive mechanism in the response to mild voluntary exercise. In addition, and in a reversal of the situation seen in heart failure, voluntary exercise training maintains the beta1-AR response but reduces the beta2-AR response. Therefore, although voluntary exercise induces cardiac hypertrophy, there are distinct differences between its effects on key myocardial regulatory mechanisms and those of hypertrophic stimuli that eventually cause cardiac decompensation.}, }
@article {pmid18478219, year = {2008}, author = {Thurgood, LA and Grover, PK and Ryall, RL}, title = {High calcium concentration and calcium oxalate crystals cause significant inaccuracies in the measurement of urinary osteopontin by enzyme linked immunosorbent assay.}, journal = {Urological research}, volume = {36}, number = {2}, pages = {103-110}, pmid = {18478219}, issn = {0300-5623}, support = {1R01-DK-064050-01A1/DK/NIDDK NIH HHS/United States ; }, mesh = {Biomarkers/urine ; Calcium/*metabolism/urine ; Calcium Oxalate/*metabolism/pharmacology ; Crystallization ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Osteopontin/chemistry/metabolism/*urine ; Protein Binding ; Reproducibility of Results ; Urolithiasis/metabolism/urine ; }, abstract = {Strong evidence that osteopontin (OPN) is a determinant of urolithiasis has prompted studies comparing the protein's urinary excretion in healthy subjects and stone formers. However, reported mean urinary values have varied widely, from <1 microg/mL to more than 20 times that value. Since OPN binds to CaOx crystals, the presence of crystals in urine may cause underestimation of its urinary levels. Using a commercial ELISA, we measured urinary OPN levels in the presence of endogenous or exogenous CaOx monohydrate (COM) and dihydrate (COD) crystals. OPN concentrations decreased in the presence of endogenous and exogenous CaOx crystals, but never below 2 microg/mL. Increasing the urinary calcium concentration decreased detectable OPN levels, possibly as a result of changes in the three-dimensional conformation of the protein. Because calcium concentration and the formation of CaOx crystals cannot be controlled in urine, the use of urinary OPN levels as a biomarker for any human pathology must be seriously questioned, but particularly for the investigation of stone formers in whom hypercalciuria and crystalluria are more common than in healthy subjects.}, }
@article {pmid18408896, year = {2008}, author = {Doddola, S and Pasupulati, H and Koganti, B and Prasad, KV}, title = {Evaluation of Sesbania grandiflora for antiurolithiatic and antioxidant properties.}, journal = {Journal of natural medicines}, volume = {62}, number = {3}, pages = {300-307}, pmid = {18408896}, issn = {1861-0293}, mesh = {Administration, Oral ; Animals ; Antioxidants/isolation &amp; purification/*pharmacology/toxicity ; Behavior, Animal/drug effects ; Calcium/metabolism ; Calcium Oxalate/metabolism ; India ; Kidney/drug effects/pathology ; Kidney Calculi/*drug therapy ; Lethal Dose 50 ; Male ; Medicine, Traditional ; Organ Size/drug effects ; Plant Extracts/*pharmacology/toxicity ; Plant Leaves ; Rats ; Rats, Wistar ; Sesbania/*chemistry ; Toxicity Tests, Acute ; }, abstract = {In the indigenous system of medicine in India, the plant Sesbania grandiflora is claimed to be useful for various ailments, and one such use is for the treatment of renal calculi. The major purpose of this study is to investigate the potential of S. grandiflora in the treatment of renal calculi. The leaf juice of S. grandiflora was evaluated for median lethal dose, gross behavioral changes, antiurolithiatic and antioxidant activities. The antiurolithiatic activity was evaluated by a calculi-producing diet model, using gentamicin (subcutaneously) and 5% ammonium oxalate in rat feed to induce calcium oxalate-type stones. The parameters monitored in the present study are calcium and oxalate deposition in the kidney, kidney weights, urinary excretion of calcium and oxalate. The in vivo antioxidant parameters lipid peroxidation, glutathione reductase and catalase were monitored. The plant juice was also evaluated for scavenging of nitric oxide and 2-diphenyl-2-picryl hydrazyl free radicals. The leaf juice of S. grandiflora was safe orally and exhibited no gross behavioral changes except for an increase in urination. The leaf juice of S. grandiflora showed significant antiurolithiatic activity against calcium oxalate-type stones and also exhibited antioxidant properties. The results obtained in this study provide evidence for the efficacy of the leaf juice of S. grandiflora as antiurolithiatic agent.}, }
@article {pmid18398019, year = {2008}, author = {Pasch, A and Frey, FJ and Eisenberger, U and Mohaupt, MG and Bonny, O}, title = {PTH and 1.25 vitamin D response to a low-calcium diet is associated with bone mineral density in renal stone formers.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {23}, number = {8}, pages = {2563-2570}, doi = {10.1093/ndt/gfn091}, pmid = {18398019}, issn = {1460-2385}, mesh = {Adult ; Bone Density/*physiology ; Calcitriol/*blood ; Calcium/blood/urine ; Calcium, Dietary/*administration &amp; dosage ; Cohort Studies ; Female ; Humans ; Hypercalciuria/complications/metabolism ; Kidney Calculi/complications/metabolism ; Lumbar Vertebrae ; Male ; Middle Aged ; Parathyroid Hormone/*blood ; Prospective Studies ; }, abstract = {BACKGROUND: Renal calcium stones and hypercalciuria are associated with a reduced bone mineral density (BMD). Therefore, the effect of changes in calcium homeostasis is of interest for both stones and bones. We hypothesized that the response of calciuria, parathyroid hormone (PTH) and 1.25 vitamin D to changes in dietary calcium might be related to BMD.<br><br>METHODS: A single-centre prospective interventional study of 94 hyper- and non-hypercalciuric calcium stone formers consecutively retrieved from our stone clinic. The patients were investigated on a free-choice diet, a low-calcium diet, while fasting and after an oral calcium load. Patient groups were defined according to lumbar BMD (z-score) obtained by dual X-ray absorptiometry (group 1: z-score <-0.5, n = 30; group 2: z-score -0.5-0.5, n = 36; group 3: z-score >0.5, n = 28). The effect of the dietary interventions on calciuria, 1.25 vitamin D and PTH in relation to BMD was measured.<br><br>RESULTS: An inverse relationship between BMD and calciuria was observed on all four calcium intakes (P = 0.009). On a free-choice diet, 1.25 vitamin D and PTH levels were identical in the three patient groups. However, the relative responses of 1.25 vitamin D and PTH to the low-calcium diet were opposite in the three groups with the highest increase of 1.25 vitamin D in group 1 and the lowest in group 3, whereas PTH increase was most pronounced in group 3 and least in group 1.<br><br>CONCLUSION: Calcium stone formers with a low lumbar BMD exhibit a blunted response of PTH release and an apparently overshooting production of 1.25 vitamin D following a low-calcium diet.}, }
@article {pmid18359393, year = {2008}, author = {Worcester, EM and Coe, FL}, title = {New insights into the pathogenesis of idiopathic hypercalciuria.}, journal = {Seminars in nephrology}, volume = {28}, number = {2}, pages = {120-132}, pmid = {18359393}, issn = {0270-9295}, support = {P01 DK056788/DK/NIDDK NIH HHS/United States ; P01 DK056788-01/DK/NIDDK NIH HHS/United States ; P01 56788//PHS HHS/United States ; }, mesh = {Animals ; Calcitriol/metabolism ; Calcium/metabolism ; Calcium, Dietary/pharmacology ; Humans ; Hypercalciuria/etiology/metabolism/*physiopathology ; Intestinal Absorption ; Kidney Calculi/complications ; }, abstract = {Idiopathic hypercalciuria (IH) is the most common metabolic abnormality in patients with calcium kidney stones. It is characterized by normocalcemia, absence of diseases that cause increased urine calcium, and calcium excretion that is greater than 250 mg/d in women and 300 mg/d in men. Subjects with IH have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, a negative calcium balance is seen commonly in balance studies, especially on a low-calcium diet. The mediator of decreased renal calcium reabsorption is not clear; it is not associated with either an increase in filtered load of calcium or altered parathyroid hormone levels. There is an increased incidence of hypercalciuria in first-degree relatives of those with IH, but IH appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion. Increased tissue vitamin D response may be responsible for the manifestations of IH in at least some patients.}, }
@article {pmid18358304, year = {2008}, author = {Kaneko, K and Ono, Y and Tainaka, T and Sumida, W and Ando, H}, title = {Fatty acid calcium stones in patients with pancreaticobiliary maljunction/choledochal cyst as another cause of obstructive symptoms besides protein plugs.}, journal = {Journal of pediatric surgery}, volume = {43}, number = {3}, pages = {564-567}, doi = {10.1016/j.jpedsurg.2007.11.004}, pmid = {18358304}, issn = {1531-5037}, mesh = {Bile Ducts/abnormalities ; Calcium/metabolism ; Child, Preschool ; Cholangiopancreatography, Endoscopic Retrograde ; Choledochal Cyst/*complications/diagnosis/*surgery ; Choledocholithiasis/diagnosis/*etiology/*surgery ; Fatty Acids/metabolism ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Pancreatic Ducts/abnormalities ; Risk Assessment ; Treatment Outcome ; }, abstract = {Symptoms of choledochal cysts are caused by protein plugs, which clog up in the long common channel and increase pancreaticobiliary ductal pressure. We report that fatty calcium acid stones/debris are another previously unreported cause of obstructive symptoms in 2 cases with choledochal cyst.}, }
@article {pmid18336098, year = {2007}, author = {Moyano, MJ and Gómez de Tejada, MJ and García Lozano, R and Moruno, R and Ortega, R and Martí, V and Sánchez Palencia, R and Miranda, MJ and Palma, A and Pérez Cano, R}, title = {[Alterations in bone mineral metabolism in patients with calcium kidney stone disease and polymorphism of vitamin D receptor. Preliminary results].}, journal = {Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia}, volume = {27}, number = {6}, pages = {694-703}, pmid = {18336098}, issn = {0211-6995}, mesh = {Adolescent ; Adult ; Aged ; Bone and Bones/*metabolism ; Calcium/*metabolism ; Case-Control Studies ; Female ; Humans ; Kidney Calculi/*genetics/*metabolism ; Male ; Middle Aged ; *Polymorphism, Genetic ; Receptors, Calcitriol/*genetics ; }, abstract = {UNLABELLED: Bone health, within calcium kidney stone disease is a matter of controversy. On the other hand, some genetic studies have shown an association between some Vitamin D receptor polymorphisms and calcium kidney stone disease.<br><br>MAIN OBJECTIVE: To study the possible association between calcium kidney stone disease with bone metabolism and some Vitamin D receptor polymorphisms.<br><br>PATIENTS AND METHODS: This is a case-control study, with seventy-two subjects of both genders divided into two groups: Group I: cases, composed by 51 patients suffering from calcium kidney stone disease. Twenty-four of them had no hypercalciuria, 16 had absortive hypercalciuria and 11 had renal hypercalciuria. Group II: controls, composed by 21 people, without either urolithiasis or hypercalciuria. We performed a complete study including biochemical markers of bone mineral remodelling, bone mineral density (BMD) was estimated both in the lumbar spine (L2-L4) and femoral neck, and also VDR polymorphism for the loci b, a and t.<br><br>RESULTS: Patients with urolithiasis had lower values of BMD both in the lumbar spine and femoral neck, compared to controls. Z-score were lower in the lumbar spine and femoral neck (p =0,045 y 0,031, respectively). Those patients with absorptive hypercalciuria had higher BMD in the femoral neck than those with renal hypercalciuria and non-hypercalciuria. Because they had more weight and height all the statistical study was performed alter adjusting by these two variables and statistical significance was then only stated between patients with hypercalciuria and without it. Patients with urolithiasis had higher values of 1,25 (OH)2 vitamin D (p=0,002), and lower of PTH (p=0,049), without any relationship to hypercalciuria and its subtypes. Seventy six percent of the patients had a daily calcium intake lower than 800 mg/day. The distribution of VDR alleles in patients with urolithiasis was similar to controls, although after grouping genotypes, a lower distribution of BB and tt polymorphisms were observed in patients suffering from urolithiasis.<br><br>CONCLUSIONS: Calcium kidney stone disease by itself produces a decrease in BMD, more intense in femoral neck, independently the presence or absence of hypercalciuria. Patients suffering from urolitihiasis have higher values of 1,25 (OH)2 vitamin D than non-hypercalciuric patients and lower values of PTH probably due to a low dietary calcium intake. In our population studied there is no relationship between VDR polymorphisms and the presence of calcium kidney stone disease. Because the reduced number of patients of our study, more studies are needed to obtain definitely conclusions.}, }
@article {pmid18335253, year = {2008}, author = {Porowski, T and Zoch-Zwierz, W and Konstantynowicz, J and Taranta-Janusz, K}, title = {A new approach to the diagnosis of children's urolithiasis based on the Bonn Risk Index.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {23}, number = {7}, pages = {1123-1128}, pmid = {18335253}, issn = {0931-041X}, mesh = {Adolescent ; Calcium Oxalate/*urine ; Case-Control Studies ; Child ; Child, Preschool ; Citrates/urine ; Cross-Sectional Studies ; Crystallization ; Female ; *Health Status Indicators ; Humans ; Hydrogen-Ion Concentration ; Hypercalciuria/complications/urine ; Hyperoxaluria/complications/urine ; Male ; Predictive Value of Tests ; Risk Assessment ; Risk Factors ; Ultrasonography ; *Urinalysis ; Urinary Calculi/*diagnosis/diagnostic imaging/etiology/urine ; }, abstract = {Published data on the association between calcium oxalate (CaOx) crystallization and kidney stone disease in children are scarce. The aims of this study were to determine CaOx crystallization using the Bonn Risk Index (BRI) in children with urolithiasis in comparison to healthy controls, to evaluate the relationships between BRI and urinary parameters, such as pH, calciuria, oxaluria and citraturia, and to assess the association between BRI and the size of renal stones. We compared the BRI in 142 Caucasian children and adolescents (76 girls, 66 boys) aged 3-18 years with kidney stones and 210 healthy age- and sex-matched controls without urolithiasis. Urinary ionized calcium ([Ca2+]) was measured using a selective electrode, while the onset of spontaneous crystallization was determined using a photometer and titration with 40 mmol/L ammonium oxalate (Ox2-). The calculation of the BRI value was based on the Ca2+:Ox2- ratio. High-resolution renal ultrasonography was carried out to estimate the size of the renal stones. The BRI values were 15-fold higher in children with renal stones than in healthy children without stones. The same trend was shown by BRI/kg body weight (tenfold greater in children with renal stones than in healthy children without stones), BRI/per 1.73 m2 body surface (13-fold greater) and BRI/body mass index (23-fold greater). No association was observed between BRI and the diameter of stones. Children with kidney stones, both males and females, had an increased BRI compared with subjects without urolithiasis. High BRI suggests an association with lower urinary pH, hypercalciuria, hyperoxaluria or hypocitraturia, which are all risk factors of kidney stones. An increased BRI in children, although unrelated to renal stone size, reflects the risk of calcium oxalate crystallization and may indicate early metabolic disorders leading to urolithiasis.}, }
@article {pmid18293139, year = {2008}, author = {Renkema, KY and Alexander, RT and Bindels, RJ and Hoenderop, JG}, title = {Calcium and phosphate homeostasis: concerted interplay of new regulators.}, journal = {Annals of medicine}, volume = {40}, number = {2}, pages = {82-91}, doi = {10.1080/07853890701689645}, pmid = {18293139}, issn = {0785-3890}, mesh = {25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism ; Animals ; Calcitonin/metabolism ; Calcitriol/metabolism ; Calcium/*metabolism ; Calcium Channels/physiology ; Calcium Metabolism Disorders/metabolism ; Estrogens/metabolism ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors/metabolism ; Glucuronidase/metabolism ; *Homeostasis ; Humans ; Klotho Proteins ; Mice ; Mice, Knockout ; Parathyroid Hormone/metabolism ; Phosphate Transport Proteins/physiology ; Phosphates/*metabolism ; Phosphorus Metabolism Disorders/metabolism ; Receptors, Calcium-Sensing/metabolism ; Renal Insufficiency, Chronic/physiopathology ; TRPV Cation Channels/physiology ; Tissue Kallikreins/metabolism ; }, abstract = {Calcium (Ca(2+)) and phosphate (P(i)) are essential to many vital physiological processes. Consequently the maintenance of Ca(2+) and P(i) homeostasis is essential to a healthy existence. This occurs through the concerted action of intestinal, renal, and skeletal regulatory mechanisms. Ca(2+) and P(i) handling by these organs is under tight hormonal control. Disturbances in their homeostasis have been linked to pathophysiological disorders including chronic renal insufficiency, kidney stone formation, and bone abnormalities. Importantly, the kidneys fine-tune the amount of Ca(2+) and P(i) retained in the body by altering their (re)absorption from the glomerular filtrate. The ion transport proteins involved in this process have been studied extensively. Recently, new key players have been identified in the regulation of the Ca(2+) and P(i) balance. Novel regulatory mechanisms and their implications were introduced for the antiaging hormone klotho and fibroblast growth factor member 23 (FGF23). Importantly, transgenic mouse models, exhibiting disturbances in Ca(2+) and P(i) balance, have been of great value in the elucidation of klotho and FGF23 functioning. This review highlights the current knowledge and ongoing research into Ca(2+) and P(i) homeostasis, emphasizing findings from several relevant knockout mouse models.}, }
@article {pmid18286270, year = {2008}, author = {Ryall, RL}, title = {The future of stone research: rummagings in the attic, Randall's plaque, nanobacteria, and lessons from phylogeny.}, journal = {Urological research}, volume = {36}, number = {2}, pages = {77-97}, pmid = {18286270}, issn = {0300-5623}, support = {1 R01DK064050-01A1/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biomedical Research/*trends ; Calcium/metabolism ; Homeostasis/physiology ; Humans ; Kidney Calculi/*etiology/metabolism/physiopathology ; *Phylogeny ; Proteobacteria/physiology ; }, abstract = {The prevention or cure of stone disease will be achieved only by identifying biochemical, physiological and molecular mechanisms operating before the formation of a calculus. Yet, the gradual increase in the total number of papers devoted to the study of kidney stones that has occurred since the beginning of the 21st century can be attributed almost entirely to papers concerned with the investigation of factors associated with urolithiasis after stones have already formed. The need to prevent stones by discovering how the human body routinely stops their formation in those of us who do not suffer from them is therefore as exigent as ever and a new approach to investigating the causes of stones is urgently needed. In this paper, I develop the view that stone research will best progress by examining and understanding how healthy plants and animals control the formation of biominerals. In addition to structures like bones, teeth, shells and spines, many organisms spanning the entire phylogenetic tree form intra- and extracellular granules which are use as storage depots for calcium and other important ions, which they can reclaim to maintain homeostasis or to satisfy specific needs during periods of high demand, such as shell formation, moulting or skeletal development. These electron-dense granules, which also bear an uncanny resemblance to calcified nanobacteria, are remarkably similar in general structure, size and composition to particles observed in healthy human kidneys and in Randall's plaque. Therefore, it is likely that the granules in human kidneys fulfil analogous functions to those in other organisms-particularly in calcium homeostasis. Their study in a large range of creatures has already provided a deep well of information about their structure, movement, composition, macromolecular content, synthesis and resorption, from which we can draw to quench our thirst for knowledge of basic mechanisms and events involved in the formation of human kidney stones.}, }
@article {pmid18276610, year = {2008}, author = {Suzuki, Y and Pasch, A and Bonny, O and Mohaupt, MG and Hediger, MA and Frey, FJ}, title = {Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation.}, journal = {Human molecular genetics}, volume = {17}, number = {11}, pages = {1613-1618}, doi = {10.1093/hmg/ddn048}, pmid = {18276610}, issn = {1460-2083}, mesh = {Adult ; Animals ; Calcitriol/blood ; Calcium/analysis/blood/*metabolism ; Calcium Channels/*genetics/metabolism ; Female ; Haplotypes ; Humans ; Hypercalciuria/*genetics/metabolism ; Kidney Calculi/chemistry/*genetics/metabolism ; Male ; Middle Aged ; Parathyroid Hormone/blood ; Polymorphism, Single Nucleotide ; Risk Factors ; TRPV Cation Channels/*genetics/metabolism ; Xenopus ; }, abstract = {The rate-limiting step of dietary calcium absorption in the intestine requires the brush border calcium entry channel TRPV6. The TRPV6 gene was completely sequenced in 170 renal calcium stone patients. The frequency of an ancestral TRPV6 haplotype consisting of three non-synonymous polymorphisms (C157R, M378V, M681T) was significantly higher (P = 0.039) in calcium stone formers (8.4%; derived = 502, ancestral = 46) compared to non-stone-forming individuals (5.4%; derived = 645, ancestral = 37). Mineral metabolism was investigated on four different calcium regimens: (i) free-choice diet, (ii) low calcium diet, (iii) fasting and (iv) after a 1 g oral calcium load. When patients homozygous for the derived haplotype were compared with heterozygous patients, no differences were found with respect to the plasma concentrations of 1,25-vitamin D, PTH and calcium, and the urinary excretion of calcium. In one stone-forming patient, the ancestral haplotype was found to be homozygous. This patient had absorptive hypercalciuria. We therefore expressed the ancestral protein (157R+378V+681T) in Xenopus oocytes and found a significantly enhanced calcium permeability when tested by a (45)Ca(2+) uptake assay (7.11 +/- 1.93 versus 3.61 +/- 1.01 pmol/min/oocyte for ancestral versus derived haplotype, P < 0.01). These results suggest that the ancestral gain-of-function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria.}, }
@article {pmid18264917, year = {2008}, author = {Cirillo, M and Iudici, M and Marcarelli, F and Laudato, M and Zincone, F}, title = {[Nephrolithiasis in patients with intestinal diseases].}, journal = {Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia}, volume = {25}, number = {1}, pages = {42-48}, pmid = {18264917}, issn = {0393-5590}, mesh = {Calcium/metabolism ; Citrates/therapeutic use ; Fluid Therapy ; Humans ; Hydrogen-Ion Concentration ; Inflammatory Bowel Diseases/complications/metabolism ; Intestinal Absorption ; Intestinal Diseases/*complications/metabolism ; Kidney Tubules/metabolism ; Malabsorption Syndromes/complications/diet therapy/metabolism ; Nephrolithiasis/drug therapy/*etiology/metabolism/prevention &amp; control ; Oxalates/metabolism ; Purines/metabolism ; Uric Acid/metabolism ; Urine/chemistry ; Vitamin D/metabolism ; }, abstract = {Intestinal diseases may cause the formation of urinary stones through changes in the metabolism of oxalate, calcium, and uric acid. The oxalate that is excreted into urine comes from the catabolism of ascorbic acid and some amino acids or from intestinal absorption of food oxalate. Calcium is absorbed by the gut after the stimulation of active vitamin D and is excreted by the kidney under the control of the bone/parathyroid hormone axis. Uric acid is generated by the oxidation of exogenous and endogenous purine bases, is excreted by the kidney through glomerular filtration/tubular secretion, and is soluble in alkaline urine. Several data indicate that patients with inflammatory bowel diseases are at high risk of urinary stones containing calcium-oxalate salt or uric acid. Calcium-oxalate stones are caused by colonic oxalate hyperabsorption (secondary to intestinal dysfunction) or by parenteral nutrition. Uric acid stones are typical of patients with severe diarrhea and/or intestinal neostomy, that is, in patients with hyperconcentrated acidic urine. Relationships between malabsorptive intestinal diseases and urinary stones are less well defined. Preventive countermeasures are not the same for all disorders. Hyperoxaluria should be controlled by diets with a low content of lipids and oxalate but supplemented with calcium and probiotics. The presence of hyperconcentrated acidic urine should be controlled by correct hydration and administration of citrate.}, }
@article {pmid18219300, year = {2008}, author = {Obligado, SH and Goldfarb, DS}, title = {The association of nephrolithiasis with hypertension and obesity: a review.}, journal = {American journal of hypertension}, volume = {21}, number = {3}, pages = {257-264}, doi = {10.1038/ajh.2007.62}, pmid = {18219300}, issn = {0895-7061}, mesh = {Calcium/metabolism ; Diabetes Mellitus, Type 2/complications/physiopathology ; Humans ; Hypertension/*epidemiology/physiopathology ; Insulin Resistance/physiology ; Nephrolithiasis/*epidemiology/physiopathology ; Obesity/*epidemiology/physiopathology ; }, abstract = {Kidney stones affect hypertensive patients disproportionately compared to normotensive individuals. On the other hand, some prospective data suggest that a history of nephrolithiasis was associated with a greater tendency to develop hypertension. Newer epidemiologic data also link obesity and diabetes, features of the metabolic syndrome, with nephrolithiasis. In this review, the association of hypertension, diabetes, and obesity with nephrolithiasis is reviewed, and possible pathogenic mechanisms are discussed. Patients with hypertension may have abnormalities of renal calcium metabolism, but data confirming this hypothesis are inconsistent. Higher body mass index and insulin resistance (i.e., the metabolic syndrome) may be etiologic in uric acid nephrolithiasis as increasing body weight is associated with decreasing urinary pH. The possibility that common pathophysiologic mechanisms underly these diseases is intriguing, and if better understood, could potentially lead to better therapies for stone prevention. Both hypertension and stones might be addressed through lifestyle modification to prevent weight gain. Adoption of a lower sodium diet with increased fruits and vegetables and low-fat dairy products, (for example, the dietary approaches to stop hypertension(DASH) diet), may be useful to prevent both stones and hypertension. In those patients in whom dietary modification and weight loss are ineffective, thiazide diuretics are likely to improve blood pressure control and decrease calciuria.}, }
@article {pmid18203914, year = {2008}, author = {Frassetto, LA and Morris, RC and Sellmeyer, DE and Sebastian, A}, title = {Adverse effects of sodium chloride on bone in the aging human population resulting from habitual consumption of typical American diets.}, journal = {The Journal of nutrition}, volume = {138}, number = {2}, pages = {419S-422S}, doi = {10.1093/jn/138.2.419S}, pmid = {18203914}, issn = {1541-6100}, support = {M01-RR0079/RR/NCRR NIH HHS/United States ; }, mesh = {Acid-Base Equilibrium/*drug effects ; Aging ; Bone and Bones/*drug effects ; Diet/*adverse effects ; Humans ; Osteoporosis ; Sodium Chloride/*adverse effects ; United States ; }, abstract = {A typical American diet contains amounts of sodium chloride far above evolutionary norms and potassium far below those norms. It also contains larger amounts of foods that are metabolized to noncarbonic acids than to organic bases. At baseline, in a steady state, diets that contain substantial sodium chloride and diets that are net acid producing each independently induce and sustain increased acidity of body fluid. With increasing age, the kidney's ability to excrete daily net acid loads declines, invoking homeostatically increased utilization of base stores (bone, skeletal muscle) on a daily basis to mitigate the otherwise increasing baseline metabolic acidosis, which results in increased calciuria and net losses of body calcium. Those effects of net acid production and its attendant increased body fluid acidity may contribute to development of osteoporosis and renal stones, loss of muscle mass, and age-related renal insufficiency. The inverted ratio of potassium to sodium in the diet compared with preagricultural diets affects cardiovascular function adversely and contributes to hypertension and stroke. The diet can return to its evolutionary norms of net base production inducing low-grade metabolic alkalosis and a high potassium-to-sodium ratio by 1) greatly reducing content of energy-dense nutrient-poor foods and potassium-poor acid-producing cereal grains, which would entail increasing consumption of potassium-rich net base-producing fruits and vegetables for maintenance of energy balance, and 2) greatly reducing sodium chloride consumption. Increasingly, evidence supports the health benefits of reestablishing evolutionary norms of dietary net base loads and high potassium and low sodium chloride loads. We focus here on the American diet's potential effects on bone through its superphysiologic content of sodium chloride.}, }
@article {pmid18190622, year = {2008}, author = {Stejskal, D and Karpisek, M and Vrtal, R and Student, V and Solichova, P and Fiala, R and Stejskal, P}, title = {Urine fetuin-A values in relation to the presence of urolithiasis.}, journal = {BJU international}, volume = {101}, number = {9}, pages = {1151-1154}, doi = {10.1111/j.1464-410X.2007.07432.x}, pmid = {18190622}, issn = {1464-410X}, mesh = {Case-Control Studies ; Crystallization ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Sensitivity and Specificity ; Urolithiasis/blood/*pathology/urine ; alpha-Fetoproteins/*metabolism/urine ; }, abstract = {OBJECTIVE: To investigate the relationship of urine fetuin-A and other promotors and inhibitors of urine crystalization with urolithiasis, as fetuin-A inhibits the precipitation of hydroxyapatite from supersaturated solutions of calcium and phosphate in vitro but no information on urine fetuin-A in patients with urolithiasis is available.<br><br>PATIENTS AND METHODS: In all, 39 patients with urolithiasis and 22 individuals with no urolithiasis or probands with undetected stones were involved. All patients underwent kidney ultrasonography and X-ray examination, and body mass index (BMI) was calculated. Serum creatinine, parathyroid hormone, calcium, magnesium, anorganic phosphate, uric acid and urine creatinine, albumin, alpha(1)-microglobulin, sulphate, oxalate, citrate and fetuin-A (ELISA) were determined.<br><br>RESULTS: The patients with urolithiasis had lower urine fetuin-A levels (median 4.9 vs 0.77 mg/day; P < 0.01) and citraturia levels (1.7 vs 5.1 mmol/day; P = 0.02); and higher calciuria (6.5 vs 5.2 mmol/day) and oxaluria (0.47 vs 0.25; P = 0.04). Patients with fetuin-A levels in the lowest quartile had an odds ratio of 36 compared with individuals in the highest quartile. The sensitivity of the urine fetuin-A level for urolithiasis was 97.4% and specificity was 100% (area under the curve 0.99; 95% confidence interval 0.94-1.0) using a urine fetuin-A threshold of <or=2.1 mg/day. Values of urine fetuin-A did not correlate with gender, age or BMI.<br><br>CONCLUSIONS: Our study indicates, for the first time, that patients with documented urolithiasis had lower fetuin-A concentrations independent of other conventional promotors and inhibitors of urine crystallization.}, }
@article {pmid17726349, year = {2007}, author = {Vella, M and Karydi, M and Coraci, G and Oriti, R and Melloni, D}, title = {Pathophysiology and clinical aspects of urinary lithiasis.}, journal = {Urologia internationalis}, volume = {79 Suppl 1}, number = {}, pages = {26-31}, doi = {10.1159/000104438}, pmid = {17726349}, issn = {0042-1138}, mesh = {Calcium/metabolism ; Cystine/metabolism ; Cystinuria/complications/urine ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Hypercalciuria/complications/urine ; Hyperoxaluria/complications/urine ; Hyperuricemia/complications/urine ; Kidney/abnormalities ; Oxalic Acid/metabolism ; Uric Acid/metabolism ; Urinary Tract Infections/complications ; Urogenital Abnormalities/complications ; Urolithiasis/*etiology/*metabolism/physiopathology/urine ; Xanthine/metabolism ; }, abstract = {Urine is a complex balanced solution containing dissociated and non-dissociated solutes. Any variation in urine saturation grade (number of crystals dissolved in a volume of urine), urinary pH and the concentration of crystallization inhibitors can break the normal existing balance and lead to urolithiasis. In the present article we analyze the principal mechanisms (absorptive, renal, resorptive) of hypercalciuria. It will be also shown how heredity directly influences the clinical aspects of cystine, xanthine and oxalate lithiasis and how diet, in association with metabolic disorders, interferes in uric acid and oxalate stone formation. Finally, we report on the roles of urinary tract malformations, urinary tract infections and drugs in the clinical characterization of urolithiasis.}, }
@article {pmid17880300, year = {2007}, author = {Kato, Y and Taniguchi, N and Okuyama, M and Kakizaki, H}, title = {Three cases of urolithiasis associated with sarcoidosis: a review of Japanese cases.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {14}, number = {10}, pages = {954-956}, doi = {10.1111/j.1442-2042.2007.01854.x}, pmid = {17880300}, issn = {0919-8172}, mesh = {Adult ; Calcium/blood/urine ; Female ; Humans ; Japan/epidemiology ; Male ; Middle Aged ; Prevalence ; Sarcoidosis/*complications/diagnosis/epidemiology/metabolism ; Urolithiasis/*complications/diagnosis/epidemiology/metabolism ; }, abstract = {We report three cases of urolithiasis associated with sarcoidosis and reviewed the Japanese published reports. All cases had hypercalcemia, hyperuricemia, hypercalciuria and renal dysfunction. A serum level of 1,25-(OH)2D3 was elevated and intact parathyroid hormone (PTH) was decreased. Stone components were predominantly calcium oxalate. Abnormal calcium metabolism is a well-known feature of sarcoidosis and the reported prevalence of urolithiasis in patients with sarcoidosis was 1.3-14.0% in the English published reports. However, urolithiasis associated with sarcoidosis is uncommon in Japan and we could find only 16 documented cases including ours. Abnormal calcium metabolism is caused by an increase in serum concentration of 1,25-(OH)2D3, which is derived from endogenous overproduction in the pulmonary macrophages. If patients with urolithiasis have abnormal calcium metabolism, renal impairment and suppression of PTH, the possibility of sarcoidosis should be considered for a differential diagnosis. Also, it should be emphasized that the presence or developing of urolithiasis is to be monitored during follow up of patients with sarcoidosis.}, }
@article {pmid17853052, year = {2007}, author = {Dussol, B and Verdier, JM and Goff, JM and Berthezene, P and Berland, Y}, title = {Artificial neural networks for assessing the risk factors for urinary calcium stones according to gender and family history of stone.}, journal = {Scandinavian journal of urology and nephrology}, volume = {41}, number = {5}, pages = {414-418}, doi = {10.1080/00365590701365263}, pmid = {17853052}, issn = {0036-5599}, mesh = {Adolescent ; Adult ; Calcium Oxalate/*metabolism ; Case-Control Studies ; *Family ; Female ; Humans ; Kidney Calculi/*pathology ; Male ; Middle Aged ; *Neural Networks, Computer ; Predictive Value of Tests ; ROC Curve ; Risk Factors ; Sensitivity and Specificity ; *Sex Characteristics ; }, abstract = {OBJECTIVE: In a previous work, we evidenced that artificial neural networks (ANNs) were more informative than classical statistical analyses for assessing the risk of idiopathic calcium nephrolithiasis in male stone-formers.<br><br>MATERIAL AND METHODS: We compared risk factors for idiopathic calcium nephrolithiasis (age, body mass index, calcemia, calcium oxalate supersaturation, and 24-h calciuria, oxaluria, uricosuria, citraturia, urea, and sodium) in four populations: men and women with and without a family history of stone (FHS). A total of 119 males (58 with an FHS, 61 without) and 59 females (30 with an FHS, 29 without) were compared to healthy controls. For each variable, receiver operating characteristic (ROC) curve indices were calculated by means of ANNs.<br><br>RESULTS: In men without an FHS, the most discriminant variables were 24-h urea (ROC curve index 0.76), supersaturation (ROC curve index 0.72), 24-h calciuria (ROC curve index 0.68), 24-h uricosuria (ROC curve index 0.64), 24-h oxaluria (ROC curve index 0.63), 24-h sodium (ROC curve index 0.62), and calcemia (ROC curve index 0.60). In men with an FHS, only supersaturation (ROC curve index 0.67) was discriminant. In women without FHS, calcemia (ROC curve index 0.67), 24-h calciuria (ROC curve index 0.64), and 24-h uricosuria (ROC curve index 0.62) were discriminant. In women with an FHS, supersaturation (ROC curve index 0.70), 24-h uricosuria (ROC curve index 0.69), 24-h urea (ROC curve index 0.68), and 24-h calciuria (ROC curve index 0.67) were discriminant.<br><br>CONCLUSIONS: Risk factors for idiopathic calcium nephrolithiasis were roughly the same in men with or without an FHS, and in women with an FHS. In these patients, calcium oxalate supersaturation and 24-h urea were the most discriminant factors. Conversely, in women without an FHS, calcium abnormalities (calcemia, 24-h calciuria) were discriminant and should prompt a search for infraclinical primary hyperparathyroidism or sarcoidosis.}, }
@article {pmid17708714, year = {2007}, author = {Oz, OK and Hajibeigi, A and Howard, K and Cummins, CL and van Abel, M and Bindels, RJ and Word, RA and Kuro-o, M and Pak, CY and Zerwekh, JE}, title = {Aromatase deficiency causes altered expression of molecules critical for calcium reabsorption in the kidneys of female mice *.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {22}, number = {12}, pages = {1893-1902}, doi = {10.1359/jbmr.070808}, pmid = {17708714}, issn = {0884-0431}, support = {HD01463/HD/NICHD NIH HHS/United States ; P01DK20543/DK/NIDDK NIH HHS/United States ; }, mesh = {Absorption ; Animals ; Aromatase/*deficiency ; Calbindin 1 ; Calbindins ; Calcium/*metabolism ; Calcium Channels/biosynthesis/genetics ; Estradiol/metabolism ; Female ; *Gene Expression Regulation/genetics ; Glucuronidase/biosynthesis/genetics ; Hypercalciuria/genetics/metabolism ; Kidney Calculi/genetics/*metabolism ; Kidney Tubules, Proximal/*metabolism ; Klotho Proteins ; Menopause/genetics/*metabolism ; Mice ; Mice, Knockout ; Plasma Membrane Calcium-Transporting ATPases/biosynthesis/genetics ; S100 Calcium Binding Protein G/biosynthesis/genetics ; Sodium-Calcium Exchanger/biosynthesis/genetics ; TRPV Cation Channels/biosynthesis/genetics ; }, abstract = {UNLABELLED: Kidney stones increase after menopause, suggesting a role for estrogen deficiency. ArKO mice have hypercalciuria and lower levels of calcium transport proteins, whereas levels of the klotho protein are elevated. Thus, estrogen deficiency is sufficient to cause altered renal calcium handling.<br><br>INTRODUCTION: The incidence of renal stones increases in women after menopause, implicating a possible role for estrogen deficiency. We used the aromatase deficient (ArKO) mouse, a model of estrogen deficiency, to test the hypothesis that estrogen deficiency would increase urinary calcium excretion and alter the expression of molecular regulators of renal calcium reabsorption.<br><br>MATERIALS AND METHODS: Adult female wildtype (WT), ArKO, and estradiol-treated ArKO mice (n = 5-12/group) were used to measure urinary calcium in the fed and fasting states, relative expression level of some genes involved in calcium reabsorption in the distal convoluted tubule by real-time PCR, and protein expression by Western blotting or immunohistochemistry. Plasma membrane calcium ATPase (PMCA) activity was measured in kidney membrane preparations. ANOVA was used to test for differences between groups followed by posthoc analysis with Dunnett's test.<br><br>RESULTS: Compared with WT, urinary Ca:Cr ratios were elevated in ArKO mice, renal mRNA levels of transient receptor potential cation channel vallinoid subfamily member 5 (TRPV5), TRPV6, calbindin-D28k, the Na+/Ca+ exchanger (NCX1), and the PMCA1b were significantly decreased, and klotho mRNA and protein levels were elevated. Estradiol treatment of ArKO mice normalized urinary calcium excretion, renal mRNA levels of TRPV5, calbindin-D(28k), PMCA1b, and klotho, as well as protein levels of calbindin-D28k and Klotho. ArKO mice treated with estradiol had significantly greater PMCA activity than either untreated ArKO mice or WT mice.<br><br>CONCLUSIONS: Estrogen deficiency caused by aromatase inactivation is sufficient for renal calcium loss. Changes in estradiol levels are associated with coordinated changes in expression of many proteins involved in distal tubule calcium reabsorption. Estradiol seems to act at the genomic level by increasing or decreasing (klotho) protein expression and nongenomically by increasing PMCA activity. PMCA, not NCX1, is likely responsible for extruding calcium in response to in vivo estradiol hormonal challenge. These data provide potential mechanisms for regulation of renal calcium handling in response to changes in serum estrogen levels.}, }
@article {pmid17481392, year = {2007}, author = {Colburn, RW and Lubin, ML and Stone, DJ and Wang, Y and Lawrence, D and D'Andrea, MR and Brandt, MR and Liu, Y and Flores, CM and Qin, N}, title = {Attenuated cold sensitivity in TRPM8 null mice.}, journal = {Neuron}, volume = {54}, number = {3}, pages = {379-386}, doi = {10.1016/j.neuron.2007.04.017}, pmid = {17481392}, issn = {0896-6273}, mesh = {Analysis of Variance ; Animals ; Behavior, Animal/drug effects ; Calcium/metabolism ; Capsaicin/pharmacology ; Cells, Cultured ; *Cold Temperature ; Ganglia, Spinal/cytology ; Inflammation/chemically induced/genetics/physiopathology ; Methanol/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout/*physiology ; Motor Activity/drug effects/genetics ; Neurons, Afferent/drug effects/physiology ; Pain Measurement/methods ; Pyrimidinones/pharmacology ; Reaction Time/drug effects ; TRPM Cation Channels/*deficiency ; Thermosensing/*genetics ; }, abstract = {Thermosensation is an essential sensory function that is subserved by a variety of transducer molecules, including those from the Transient Receptor Potential (TRP) ion channel superfamily. One of its members, TRPM8 (CMR1), a ligand-gated, nonselective cation channel, is activated by both cold and chemical stimuli in vitro. However, its roles in cold thermosensation and pain in vivo have not been fully elucidated. Here, we show that sensory neurons derived from TRPM8 null mice lack detectable levels of TRPM8 mRNA and protein and that the number of these neurons responding to cold (18 degrees C) and menthol (100 microM) is greatly decreased. Furthermore, compared with WT mice, TRPM8 null mice display deficiencies in certain behaviors, including icilin-induced jumping and cold sensation, as well as a significant reduction in injury-induced responsiveness to acetone cooling. These results suggest that TRPM8 may play an important role in certain types of cold-induced pain in humans.}, }
@article {pmid17476495, year = {2007}, author = {Odvina, CV and Sakhaee, K and Heller, HJ and Peterson, RD and Poindexter, JR and Padalino, PK and Pak, CY}, title = {Biochemical characterization of primary hyperparathyroidism with and without kidney stones.}, journal = {Urological research}, volume = {35}, number = {3}, pages = {123-128}, pmid = {17476495}, issn = {0300-5623}, support = {M01 RR00633/RR/NCRR NIH HHS/United States ; P01 DK20543/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Calcium/*metabolism/urine ; Calcium Oxalate/urine ; Calcium Phosphates/urine ; Citrates/urine ; Female ; Humans ; Hyperparathyroidism, Primary/*complications/physiopathology/*urine ; Intestinal Absorption/physiology ; Kidney Calculi/*etiology/physiopathology/*urine ; Male ; Middle Aged ; Phosphorus/urine ; Retrospective Studies ; }, abstract = {The exact metabolic-physiological background for kidney stone formation in primary hyperparathyroidism (PHPT) is unclear. To obtain clarification, this retrospective data analysis was conducted in 131 patients with PHPT who had undergone a detailed ambulatory evaluation on a random diet since 1980. The baseline biochemical presentation of 78 patients with PHPT with stones was compared with that of 53 patients without stones. Compared to those without stones, the stone-forming patients had a more marked hypercalciuria (343 +/- 148 vs. 273 +/- 148 mg/day, P < 0.01). Urinary saturation of calcium oxalate and brushite was significantly higher in stone-formers. Serum PTH and fasting urinary calcium were similar between the two groups, but serum phosphorus was significantly lower in stone-formers. Serum calcitriol (available in some patients) showed a slightly higher mean value in stone-formers but the difference was not significant. The increment in urinary calcium after oral load of 1-g calcium was twofold higher among stone-formers. Radial shaft and L2-L4 bone mineral densities resided within the normal ranges. Stone-formers with PHPT display exaggerated urinary calcium excretion due to intestinal hyperabsorption of calcium, contributing to a greater enhancement of the saturation of stone-forming calcium salts.}, }
@article {pmid17432687, year = {2007}, author = {Zhang, XB and Cui, NQ and Li, DH}, title = {[Effect of clearing heat and removing dampness method on formation of pigment gallstones in rabbits].}, journal = {Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine}, volume = {27}, number = {3}, pages = {241-243}, pmid = {17432687}, issn = {1003-5370}, mesh = {Animals ; Bile/drug effects/metabolism ; Bile Pigments/*metabolism ; Calcium/metabolism ; Drugs, Chinese Herbal/*therapeutic use ; Female ; Gallstones/*drug therapy/metabolism/pathology ; Glucuronidase/metabolism ; Male ; Phytotherapy ; Rabbits ; Random Allocation ; Treatment Outcome ; }, abstract = {OBJECTIVE: To observe dynamically the effect of drugs for clearing heat and removing dampness (CHRD) on biliary components in rabbits with pigment gallstones (PGS).<br><br>METHODS: Forty rabbits were established into PGS model and randomly divided into 3 groups, the bacterial infection group, the CHRD low-dose group and the CHRD high-dose group. Besides, a normal group was set up with healthy rabbits for control. Changes of total bilirubin (TB), unconjugated bilirubin (UCB), total bile acid (TBA), Ca2+, bacterial and endogenous beta-glucuronidase (beta-Gase) in bile were observed.<br><br>RESULTS: CHRD drugs significantly decreased the contents of UCB, Ca2+, bacterial and endogenous beta-Gase (P < 0.05), and increased TBA in bile (P < 0.05).<br><br>CONCLUSION: CHRD drugs have good effect in reducing the lithogenesis of the pigment gallstones.}, }
@article {pmid17419705, year = {2007}, author = {Liu, CC and Huang, CH and Wu, WJ and Huang, SP and Chou, YH and Li, CC and Chai, CY and Wu, MT}, title = {Association of vitamin D receptor (Fok-I) polymorphism with the clinical presentation of calcium urolithiasis.}, journal = {BJU international}, volume = {99}, number = {6}, pages = {1534-1538}, doi = {10.1111/j.1464-410X.2007.06792.x}, pmid = {17419705}, issn = {1464-4096}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Polymorphism, Genetic/*genetics ; Receptors, Calcitriol/*genetics ; Risk Factors ; Severity of Illness Index ; Taiwan ; Urolithiasis/*genetics ; }, abstract = {OBJECTIVE: To investigate the effect of the vitamin D receptor (VDR) FokI polymorphism on the clinical presentation of calcium urolithiasis, as a FokI polymorphism in the VDR gene was recently reported to be associated with calcium metabolism disorders.<br><br>In all, 235 patients with calcium urolithiasis and 231 age- and sex-matched healthy controls were recruited from Kaohsiung Medical University Hospital between June 2003 and February 2005. Clinical information on the age at first onset, stone episodes, stone severity and presence of family history were collected from patients with stones. Any VDR FokI polymorphism was detected using polymerase chain reaction-based restriction analysis.<br><br>RESULTS: The frequency of VDR FokI genotypes between the patients and the healthy controls was not significantly different. However, among patients, those with the FF genotype had a significantly higher risk of having more stone episodes (adjusted odds ratio 2.15, 95% confidence interval 1.02-4.54, P = 0.044) and were younger at the first onset (3.23, 1.08-9.63, P = 0.036) than those with the ff genotype.<br><br>CONCLUSION: The VDR FokI polymorphism might be important in the clinical presentation of patients with calcium urolithiasis, especially for the frequency of stone episodes and age at first onset, although it is not associated with the formation of stones.}, }
@article {pmid17393118, year = {2007}, author = {Liu, J and Cao, Z and Zhang, Z and Zhou, S and Ye, Z}, title = {A comparative study on several models of experimental renal calcium oxalate stones formation in rats.}, journal = {Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban}, volume = {27}, number = {1}, pages = {83-87}, pmid = {17393118}, issn = {1672-0733}, mesh = {Ammonium Chloride/adverse effects/metabolism/urine ; Animals ; Blood Urea Nitrogen ; Calcium/blood/metabolism/urine ; Calcium Gluconate/adverse effects/metabolism/urine ; Calcium Oxalate/metabolism/*urine ; Creatinine/blood ; Crystallization ; Disease Models, Animal ; Ethylene Glycol/adverse effects/metabolism/urine ; Gentamicins/adverse effects/metabolism/urine ; Hydroxycholecalciferols/adverse effects/metabolism/urine ; Hydroxyproline/adverse effects/metabolism/urine ; Kidney/*metabolism/pathology ; Kidney Calculi/chemically induced/*metabolism/prevention &amp; control ; Magnesium/metabolism/urine ; Male ; Microscopy, Polarization ; Oxalates/adverse effects/metabolism/urine ; Phosphorus/blood ; Random Allocation ; Rats ; Rats, Wistar ; }, abstract = {In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D(3)[1alpha(OH)VitD(3), alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D(3), the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D(3). EG plus Vitamin D(3) or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation.}, }
@article {pmid17382697, year = {2007}, author = {Huen, SC and Goldfarb, DS}, title = {Adverse metabolic side effects of thiazides: implications for patients with calcium nephrolithiasis.}, journal = {The Journal of urology}, volume = {177}, number = {4}, pages = {1238-1243}, doi = {10.1016/j.juro.2006.11.040}, pmid = {17382697}, issn = {0022-5347}, mesh = {Calcium/*metabolism ; Humans ; Nephrolithiasis/*metabolism ; Randomized Controlled Trials as Topic ; Thiazides/*adverse effects ; }, abstract = {PURPOSE: Thiazide use to prevent recurrent calcium nephrolithiasis is supported by randomized, controlled trials. Concerns regarding adverse metabolic effects of thiazides, which are also used to treat hypertension, have reemerged with analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The risks posed by thiazide induced hyperglycemia, hyperuricemia, hypokalemia and dyslipidemia may decrease the expected cardiovascular benefit of lowering blood pressure in hypertensive patients. Whether these side effects occur and are clinically significant in nonhypertensive patients with kidney stones treated with thiazides is unclear.<br><br>MATERIALS AND METHODS: A review of the literature was performed for randomized, controlled trials with thiazides for calcium nephrolithiasis. We sought data regarding metabolic effects in this population, including hyperglycemia, hyperuricemia, hypokalemia and dyslipidemia.<br><br>RESULTS: Nine randomized, controlled trials of thiazide treatment for kidney stones were included. Mean patient age was 42 years and followup was 2.6 years. Only 2 of the 9 studies measured glucose and lipid levels, which did not significantly change with treatment. Three studies measured serum potassium and 2 showed a significant decrease. Three of the 9 studies measured serum uric acid levels, which increased in all 3. None of the trials studied the development of diabetes mellitus or cardiovascular disease.<br><br>CONCLUSIONS: There is a lack of data on the metabolic effects of thiazides used to prevent recurrent calcium nephrolithiasis. It remains unclear if metabolic effects occur and increase the risk of cardiovascular disease in otherwise healthy patients with recurrent nephrolithiasis on thiazide prophylaxis. Further research is needed to elucidate other alternatives for the treatment of recurrent nephrolithiasis.}, }
@article {pmid17352876, year = {2007}, author = {Shen, P and Fang, BJ and Zhu, PT and Zhang, JZ and Pei, XJ}, title = {[Effect of traditional Chinese herbs for nourishing the liver on intracellular free calcium level in gallbladder cells of guinea pigs with gallstones].}, journal = {Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine}, volume = {5}, number = {2}, pages = {179-182}, doi = {10.3736/jcim20070216}, pmid = {17352876}, issn = {1672-1977}, mesh = {Animals ; Biological Transport, Active/drug effects ; Calcium/*metabolism ; Cholesterol, Dietary/administration &amp; dosage/toxicity ; Drugs, Chinese Herbal/*therapeutic use ; Female ; Gallbladder/*drug effects/metabolism/pathology ; Gallstones/chemically induced/*drug therapy/metabolism ; Guinea Pigs ; Male ; Phytotherapy ; Random Allocation ; }, abstract = {OBJECTIVE: To observe the changes of intracellular free calcium level ([Ca(2+)]i) in gallbladder cells of guinea pigs with gallstones so as to study the mechanisms of gallstone formation and the prevention and treatment function of traditional Chinese herbs for nourishing the liver.<br><br>METHODS: Eighty guinea pigs were randomly divided into four groups, which were normal control group, untreated group, nourishing-liver Chinese drug (NLCD) group and ursodeoxycholic acid (UDCA) group, with 20 guinea pigs in each group. Gallstones were induced in the guinea pigs of the latter 3 groups by the feed of diet inducing cholelithiasis with high cholesterol, while the corresponding medicines were used in NLCD group and UDCA group for prevention and treatment for 7 weeks. Then the state of the guinea pigs, the formation of gallstones, and the changes of [Ca(2+)]i in gallbladder cells were observed.<br><br>RESULTS: The [Ca(2+)]i in gallbladder cells of guinea pigs in the untreated group was decreased significantly. NLCD improved the behavioral signs of the guinea pigs, significantly decreased the formative rate of gallstones and increased the [Ca(2+)]i in gallbladder cells.<br><br>CONCLUSIONS: The [Ca(2+)]i in gallbladder cells is the important factor for contractile function of gallbladder and the information of gallstones. Traditional Chinese herbs for nourishing the liver may significantly increase the [Ca(2+)]i in gallbladder cells to facilitate contraction of the smooth muscle cells of gallbladder and relieve the cholestatis. It may be one of the mechanisms of traditional Chinese herbs for nourishing the liver in preventing and treating cholelithiasis.}, }
@article {pmid17227436, year = {2007}, author = {Goracke-Postle, CJ and Overland, AC and Stone, LS and Fairbanks, CA}, title = {Agmatine transport into spinal nerve terminals is modulated by polyamine analogs.}, journal = {Journal of neurochemistry}, volume = {100}, number = {1}, pages = {132-141}, doi = {10.1111/j.1471-4159.2006.04193.x}, pmid = {17227436}, issn = {0022-3042}, support = {K01 DA-00509/DA/NIDA NIH HHS/United States ; R21 DA-15387/DA/NIDA NIH HHS/United States ; T32DA007097/DA/NIDA NIH HHS/United States ; T32DA07234/DA/NIDA NIH HHS/United States ; }, mesh = {Agmatine/*metabolism ; Analysis of Variance ; Animals ; Axonal Transport/*drug effects ; Binding, Competitive/drug effects ; Biogenic Polyamines/*pharmacology ; Calcium/metabolism ; Dose-Response Relationship, Drug ; Energy Metabolism ; Male ; Microscopy, Electron, Transmission/methods ; Paraquat/pharmacology ; Putrescine/metabolism ; Pyruvaldehyde/pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves/drug effects/metabolism/*ultrastructure ; Synaptosomes/*drug effects/metabolism/ultrastructure ; Temperature ; Time Factors ; Triturus/metabolism ; }, abstract = {Agmatine (decarboxylated arginine) is an endogenous amine found in the CNS that antagonizes NMDA receptors and inhibits nitric oxide synthase. Intrathecally administered agmatine inhibits hyperalgesia evoked by inflammation, nerve injury and intrathecally administered NMDA. These actions suggest an antiglutamatergic neuromodulatory role for agmatine in the spinal cord. Such a function would require a mechanism of regulated clearance of agmatine such as neuronal or glial uptake. Consistent with this concept, radiolabeled agmatine has been shown to accumulate in synaptosomes, but the mechanism of this transport has not been fully characterized. The present study describes an agmatine uptake system in spinal synaptosomes that appears driven by a polyamine transporter. [(3)H]Agmatine uptake was Ca(2+), energy and temperature dependent. [(3)H]Agmatine transport was not moderated by L-arginine, L-glutamate, glycine, GABA, norepinephrine or serotonin. In contrast, [(3)H]agmatine uptake was concentration dependently inhibited by unlabeled putrescine and by unlabeled spermidine (at significantly higher concentrations). Similarly, [(3)H]putrescine uptake was inhibited in a concentration-dependent manner by unlabeled agmatine and spermidine. The polyamine analogs paraquat and methylglyoxal bis (guanylhydrazone) inhibited, whereas the polyamine transport enhancer difluoromethylornithine increased, [(3)H]agmatine transport. Taken together, these results suggest that agmatine transport into spinal synaptosomes may be governed by a polyamine transport mechanism.}, }
@article {pmid17210796, year = {2007}, author = {Worcester, EM and Gillen, DL and Evan, AP and Parks, JH and Wright, K and Trumbore, L and Nakagawa, Y and Coe, FL}, title = {Evidence that postprandial reduction of renal calcium reabsorption mediates hypercalciuria of patients with calcium nephrolithiasis.}, journal = {American journal of physiology. Renal physiology}, volume = {292}, number = {1}, pages = {F66-75}, doi = {10.1152/ajprenal.00115.2006}, pmid = {17210796}, issn = {1931-857X}, support = {M01 00055//PHS HHS/United States ; P01-56788//PHS HHS/United States ; }, mesh = {Adult ; Calcium/*metabolism/*urine ; Diet ; Dietary Proteins/pharmacology ; Fasting/metabolism ; Female ; Humans ; Iothalamic Acid/pharmacology ; Kidney/*metabolism ; Kidney Tubules/metabolism ; Magnesium/blood/urine ; Male ; Middle Aged ; Nephrolithiasis/*urine ; Parathyroid Hormone/blood ; Phosphates/blood/urine ; Postprandial Period/*physiology ; Sodium/urine ; }, abstract = {Idiopathic hypercalciuria (IH) is common among calcium stone formers (IHSF). The increased urinary calcium arises from increased intestinal absorption of calcium, but it is unclear whether increased filtered load or decreased renal tubular reabsorption of calcium is the main mechanism for the increased renal excretion. To explore this question, 10 IHSF and 7 normal subjects (N) were studied for 1 day. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, and calories. Fasting and fed, ultrafiltrable calcium levels, and filtered load of calcium did not differ between N and IHSF. Urine calcium rose with meals, and fractional reabsorption fell in all subjects, but the change was significantly higher in IHSF. The changes in calcium excretion were independent of sodium excretion. Serum parathyroid hormone levels did not differ between N and IHSF, and they could not account for the greater fall in calcium reabsorption in IHSF. Serum magnesium and phosphorus levels in IHSF were below N throughout the day, and tubule phosphate reabsorption was lower in IHSF than N after meals. The primary mechanism by which kidneys ferry absorbed calcium into the urine after meals is via reduced tubule calcium reabsorption, and IHSF differ from N in the magnitude of the response. Parathyroid hormone is not likely to be a sufficient explanation for this difference.}, }
@article {pmid17160655, year = {2007}, author = {Tugcu, V and Ozbek, E and Aras, B and Ozbay, B and Islim, F and Tasci, AI}, title = {Bone mineral density measurement in patients with recurrent normocalciuric calcium stone disease.}, journal = {Urological research}, volume = {35}, number = {1}, pages = {29-34}, pmid = {17160655}, issn = {0300-5623}, mesh = {*Absorptiometry, Photon ; Adult ; *Bone Density ; Bone Diseases, Metabolic/diagnostic imaging ; Calcium/*metabolism/urine ; Citrates/urine ; Female ; Femur/diagnostic imaging ; Humans ; Lumbar Vertebrae/diagnostic imaging ; Male ; Middle Aged ; Osteoporosis/diagnostic imaging ; Oxalates/urine ; Recurrence ; Urolithiasis/*diagnostic imaging/*metabolism/urine ; }, abstract = {To investigate bone mineral densitometry findings in patients with normocalciuric urinary system stone disease, we compared 150 patients with normocalciuric calcium stone disease (group 1) and 60 subjects of a control group (group 2). The patients were compared according to bone mineral content (BMC), bone area (BA), bone mineral density (BMD), T-score and Z-score values of femur neck, total femur and lumbar spine (L2-L4) by dual energy absorptiometry. We found that 76.6% of the patients in group 1 and 20.0% in group 2 had low BMD; 11.3% of patients in group 1 had osteoporosis and 65.4% had osteopenia. In the control group, there was no osteoporosis, but 20.0% of the subjects had osteopenia. In group 1, there was hyperoxaluria in 26.0% of patients, hypocitraturia in 15.3% of patients, hyperuricosuria in 6.0% of patients, both hypocitraturia and hyperoxaluria in 8.6% of patients in a 24-h urine analysis. Urine analysis was normal in 44.0% of patients. Our results showed a severe loss of bone mass in patients with urinary system normocalciuric calcium stone disease. Thus, the necessary precautions concerning bone mass protection should be taken and the patients should be informed about this issue.}, }
@article {pmid17137403, year = {2006}, author = {Vestergaard, P}, title = {Current pharmacological options for the management of primary hyperparathyroidism.}, journal = {Drugs}, volume = {66}, number = {17}, pages = {2189-2211}, pmid = {17137403}, issn = {0012-6667}, mesh = {Bone Density ; Calcium/agonists/metabolism ; Humans ; Hyperparathyroidism, Primary/*drug therapy/metabolism ; Parathyroid Hormone/metabolism ; Selective Estrogen Receptor Modulators/*therapeutic use ; }, abstract = {Drugs for treating primary hyperparathyroidism can be divided into two main groups: (i) antiresorptive drugs that inhibit the increased bone turnover, which can be divided into estrogen-like compounds (estrogen, oral contraceptives and selective estrogen receptor modulators [SERMs]), bisphosphonates and calcitonin; and (ii) drugs that interfere with parathyroid hormone (PTH) secretion (currently only cinacalcet is available). No drugs that interfere with PTH action are currently available. Available studies suggest that all classes of drugs are able to lower serum calcium levels. However, calcitonin does so only temporarily. Estrogen-containing compounds (hormone replacement therapy) may be less attractive because of the potential risk of breast cancer, cardiovascular disease and deep vein thromboembolism. Oral contraceptives have not been shown to be able to prevent fractures in the general population, and no data are available on their effect in women with primary hyperparathyroidism. The only SERM marketed for hyperparathyroidism is raloxifene and this has not been associated with an increased risk of breast cancer and cardiovascular diseases, and has been shown to be able to prevent vertebral fractures in postmenopausal women with osteoporosis. Two small trials suggest that raloxifene may increase bone mineral density (BMD) and decrease serum calcium levels in patients with primary hyperparathyroidism. Bisphosphonates have been shown to decrease serum calcium and increase BMD in patients with primary hyperparathyroidism, but PTH levels may increase. Cinacalcet effectively induces a sustained decrease in serum calcium and PTH for up to 1 year. However, BMD does not seem to increase. No data on hard endpoints such as fractures, kidney stones, cardiovascular disease etc. are available for any of the drugs available for the treatment of primary hyperparathyroidism.}, }
@article {pmid17129690, year = {2007}, author = {Brown, DM and Hutchison, L and Donaldson, K and MacKenzie, SJ and Dick, CA and Stone, V}, title = {The effect of oxidative stress on macrophages and lung epithelial cells: the role of phosphodiesterases 1 and 4.}, journal = {Toxicology letters}, volume = {168}, number = {1}, pages = {1-6}, doi = {10.1016/j.toxlet.2006.10.016}, pmid = {17129690}, issn = {0378-4274}, mesh = {3',5'-Cyclic-AMP Phosphodiesterases/antagonists &amp; inhibitors ; 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone/pharmacology ; Animals ; Calcium/metabolism ; Calcium Channel Blockers/pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases/antagonists &amp; inhibitors ; Cell Line ; Chelating Agents/pharmacology ; Cyclic Nucleotide Phosphodiesterases, Type 1 ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Egtazic Acid/analogs &amp; derivatives/pharmacology ; Epithelial Cells/*drug effects/metabolism ; Interleukin-8/metabolism ; Lung/cytology ; Macrophages/*drug effects/metabolism ; Mice ; Oxidants/*pharmacology ; *Oxidative Stress ; Phosphodiesterase Inhibitors/*pharmacology ; Sulfonamides/pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; Verapamil/pharmacology ; tert-Butylhydroperoxide/*pharmacology ; }, abstract = {Reactive oxygen species (ROS) have been implicated in various pulmonary diseases by causing direct injury to lung epithelial cells. Signalling activity of cells through transcription factors such as nuclear factor kappa B (NF-kappaB) and AP-1 have been shown to be regulated by ROS, and the release of pro-inflammatory cytokines demonstrated in the study of inflammatory disease. In this study, we examined the effect of the oxidant tert-butylhydroperoxide (tBHP) on mouse J774 macrophages and its ability to cause the release of the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha). The role of calcium as a signalling molecule was studied using various calcium antagonists. The role of the signalling molecule cAMP was also investigated using phosphodiesterase inhibitors PDE1 and PDE4 families. Oxidative stress was investigated in lung epithelial (A549) cells with and without calcium antagonists and PDE inhibitors with regard to their ability to modulate release of the neutrophil chemoattractant interleukin 8 (IL-8). The oxidant tBHP significantly increased the cytosolic calcium concentration in J774 macrophages, which was prevented by the PDE1 inhibitor. The production of TNF-alpha protein by J774 macrophages was mediated by a pathway involving calcium as addition of calcium antagonists inhibited the tBHP stimulated increase in the cytokine. Inhibitors of both PDE1 and PDE4 completely prevented the tBHP stimulated TNF-alpha release suggesting that the cAMP pathway may be important in the oxidant induced signalling pathway leading to gene expression of pro-inflammatory cytokines. In the presence of oxidant alone, A549 epithelial cells released significant amounts of IL-8, which was inhibited by both calcium antagonist treatment and PDE inhibition treatment. These data suggest that ROS-mediated lung inflammation could be mediated at least in part by calcium and elevated PDE activity associated with decreased cAMP in both macrophages and epithelial cells. Inhibition of these pathways may provide a route for treatment of inflammatory lung diseases.}, }
@article {pmid17120180, year = {2007}, author = {Bolland, MJ and Ames, RW and Horne, AM and Orr-Walker, BJ and Gamble, GD and Reid, IR}, title = {The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women.}, journal = {Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA}, volume = {18}, number = {4}, pages = {479-486}, pmid = {17120180}, issn = {0937-941X}, mesh = {Blood Chemical Analysis/methods ; Bone Density/*drug effects ; Bone Resorption/physiopathology/prevention &amp; control ; Calcium/metabolism ; Double-Blind Method ; Female ; Fractures, Bone/prevention &amp; control ; Humans ; Hydrochlorothiazide/adverse effects/*therapeutic use ; Leg Bones/physiology ; Long-Term Care/methods ; Middle Aged ; Osteoporosis, Postmenopausal/prevention &amp; control ; Postmenopause/*physiology ; Sodium Chloride Symporter Inhibitors/adverse effects/*therapeutic use ; Spine/physiology ; Treatment Outcome ; }, abstract = {SUMMARY: We performed a 2-year extension of our previous 2-year randomized controlled trial of the effects of hydrochlorothiazide on bone mineral density. The improvements in bone density seen in the first 2 years were sustained throughout the extension study. Thiazides provide a further option in the prevention of postmenopausal bone loss.<br><br>INTRODUCTION: Thiazide diuretics reduce urinary calcium excretion and therefore might prevent osteoporosis. Previously we reported a 2-year randomized controlled trial of hydrochlorothiazide treatment in 185 postmenopausal women that showed positive benefits of hydrochlorothiazide on bone density. Here, we report the results of a 2-year extension to that study.<br><br>METHODS: Of 185 healthy postmenopausal women, 122 agreed to continue in a double-blinded 2-year extension taking 50 mg hydrochlorothiazide or placebo daily. Measurements of bone density occurred every 6 months and of calcium metabolism at 2 and 4 years.<br><br>RESULTS: The improvements in bone density seen in the first 2 years of the trial were sustained throughout the extension. There were significant between-groups differences in the change in bone density over 4 years at the total body (0.9%, P<0.001), legs (1.0%, P=0.002), mid-forearm (1.1%, P=0.03), and ultradistal forearm (1.4%, P=0.04). At the lumbar spine (0.9%, P=0.76) and femoral neck (0.4%, P=0.53) the between-groups differences did not reach statistical significance.<br><br>CONCLUSIONS: Hydrochlorothiazide produces small positive benefits on cortical bone density that are sustained for at least the first 4 years of treatment. They provide a further option in the prevention of postmenopausal bone loss, especially for women with hypertension or a history of kidney stones.}, }
@article {pmid17047128, year = {2006}, author = {Belzer, C and Kusters, JG and Kuipers, EJ and van Vliet, AH}, title = {Urease induced calcium precipitation by Helicobacter species may initiate gallstone formation.}, journal = {Gut}, volume = {55}, number = {11}, pages = {1678-1679}, pmid = {17047128}, issn = {0017-5749}, mesh = {Calcium/*metabolism ; Chemical Precipitation ; Gallstones/*microbiology ; Helicobacter Infections/*complications ; Humans ; Urease/*physiology ; }, }
@article {pmid16908491, year = {2006}, author = {Silver, WL and Clapp, TR and Stone, LM and Kinnamon, SC}, title = {TRPV1 receptors and nasal trigeminal chemesthesis.}, journal = {Chemical senses}, volume = {31}, number = {9}, pages = {807-812}, doi = {10.1093/chemse/bjl022}, pmid = {16908491}, issn = {0379-864X}, support = {R01 DC 006070-03/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism ; Capsaicin/analogs &amp; derivatives/pharmacology ; Cell Line ; Humans ; Irritants/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Smell/*physiology ; Stimulation, Chemical ; TRPV Cation Channels/drug effects/genetics/*physiology ; Transfection ; Trigeminal Nerve/*physiology ; }, abstract = {The trigeminal nerve responds to a wide variety of irritants. Trigeminal nerve fibers express several receptors that respond to chemicals, including TRPV1 (vanilloid) receptors, acid-sensing ion channels, P2X (purinergic) receptors, and nicotinic acetylcholine receptors. In order to assess whether TRPV1 plays a role in responses to a broad array of substances, TRPV1 (along with green fluorescent protein) was expressed in human embyonic kidney cells (HEK) 293t cells which were then stimulated with diverse trigeminal irritants. Calcium imaging was used to measure responses to capsaicin, amyl acetate, cyclohexanone, acetic acid, toluene, benzaldehyde, (-)-nicotine, (R)-(+)-limonene, (R)-(-)-carvone, and (S)-(+)-carvone. Three irritants (acetic acid and the 2 carvones) stimulated nontransfected controls. Two irritants (capsaicin and cyclohexanone) stimulated only transfected cells. The response could be eliminated with capsazepine, a TRPV1 blocker. The 5 remaining irritants were nonstimulatory in both nontransfected and transfected cells. Because all the compounds tested on HEK cells elicited neural responses from the ethmoid branch of the trigeminal nerve in rats, the 5 nonstimulatory compounds must do so by a non-TRPV1 receptor. These results suggest that TRPV1 serves as a receptor for both cyclohexanone and capsaicin in trigeminal nerve endings.}, }
@article {pmid16855017, year = {2006}, author = {Mente, A and Honey, RJ and McLaughlin, JM and Bull, SB and Logan, AG}, title = {High urinary calcium excretion and genetic susceptibility to hypertension and kidney stone disease.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {17}, number = {9}, pages = {2567-2575}, doi = {10.1681/ASN.2005121309}, pmid = {16855017}, issn = {1046-6673}, mesh = {Adolescent ; Adult ; Calcium/*urine ; Creatinine/urine ; Family Health ; Female ; *Genetic Predisposition to Disease ; Humans ; Hypercalciuria/*epidemiology/urine ; Hypertension/epidemiology/*genetics ; Kidney Calculi/epidemiology/*genetics ; Male ; Middle Aged ; Odds Ratio ; Ontario/epidemiology ; Sodium/urine ; Uric Acid/urine ; }, abstract = {Increased urinary calcium excretion commonly is found in patients with hypertension and kidney stone disease (KSD). This study investigated the aggregation of hypertension and KSD in families of patients with KSD and hypercalciuria and explored whether obesity, excessive weight gain, and diabetes, commonly related conditions, also aggregate in these families. Consecutive patients with KSD, aged 18 to 50 yr, were recruited from a population-based Kidney Stone Center, and a 24-h urine sample was collected. The first-degree relatives of eligible patients (n = 333) and their spouse were interviewed by telephone to collect demographic and health information. Familial aggregation was assessed using generalized estimating equations. Multivariate-adjusted odds ratios (OR) revealed significant associations between hypercalciuria in patients and hypertension (OR 2.9; 95% confidence interval 1.4 to 6.2) and KSD (OR 1.9; 95% confidence interval 1.03 to 3.5) in first-degree relatives, specifically in siblings. No significant associations were found in parents or spouses or in patients with hyperuricosuria. Similarly, no aggregation with other conditions was observed. In an independent study of siblings of hypercalciuric patients with KSD, the adjusted mean fasting urinary calcium/creatinine ratio was significantly higher in the hypertensive siblings compared with normotensive siblings (0.60 +/- 0.32 versus 0.46 +/- 0.28 mmol/mmol; P < 0.05), and both sibling groups had significantly higher values than the unselected study participants (P < 0.001). Urinary sodium/creatinine and uric acid/creatinine ratios were not different among the groups. Although an environmental effect cannot be excluded fully, our findings suggest that the disturbance in calcium metabolism in hypertension and KSD has a genetic basis.}, }
@article {pmid16834669, year = {2006}, author = {Shin, JI and Park, JM and Lee, JS and Han, SW and Kim, MJ}, title = {Superimposition of nutcracker syndrome in a hematuric child with idiopathic hypercalciuria and urolithiasis.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {13}, number = {6}, pages = {814-816}, doi = {10.1111/j.1442-2042.2006.01411.x}, pmid = {16834669}, issn = {0919-8172}, mesh = {Calcium Metabolism Disorders/*diagnostic imaging/urine ; Child ; Female ; Hematuria/*diagnostic imaging/urine ; Humans ; Kidney/*blood supply/diagnostic imaging ; Kidney Diseases/*diagnostic imaging/urine ; Syndrome ; *Ultrasonography, Doppler/methods ; }, abstract = {We report a 5-year-old girl with idiopathic hypercalciuria who developed gross hematuria and left flank pain despite normalization of calciuria, a renal stone, and microscopic hematuria. She was found to have nutcracker syndrome by renal Doppler ultrasound, which revealed the significant differences of the peak blood flow velocities in the two portions of the left renal vein.}, }
@article {pmid16819644, year = {2006}, author = {Korkes, F and Segal, AB and Heilberg, IP and Cattini, H and Kessler, C and Santili, C}, title = {Immobilization and hypercalciuria in children.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {21}, number = {8}, pages = {1157-1160}, pmid = {16819644}, issn = {0931-041X}, mesh = {Child ; Female ; Hip Dislocation, Congenital/therapy ; Humans ; Hypercalciuria/*epidemiology/*etiology ; Immobilization/*adverse effects ; Infant ; Legg-Calve-Perthes Disease/therapy ; Male ; Time Factors ; }, abstract = {Intermediate-term immobilization may lead to an increase in serum and urinary calcium. In order to test this hypothesis, we evaluated 46 children, 21 with Legg-Calvé-Perthes disease (LCP; 7.2+/-1.8 years old) and 25 with developmental dysplasia of the hip joint (DDH; 10+/-5 months of age), submitted to immobilization for up to 16 weeks. These two conditions require intermediate-term immobilization as treatment modality, and no studies evaluating calcium metabolism in these groups of patients have been conducted. In LCP patients, blood and 24-h urine samples were obtained before the beginning of treatment and after 1, 6, 8, 14 and 16 weeks of immobilization, while in DDH patients, blood and spot urine samples were collected before treatment and after 6 and 14 weeks of treatment. Urinary calcium, creatinine, potassium and sodium as well as serum calcium, phosphorus, parathyroid hormone, creatinine and alkaline phosphatase were determined in those samples. Renal ultrasound was performed before and after treatment. A mean increase of 2.3 times baseline values of urinary calcium was observed in 40% of previously normocalciuric LCP patients after only 1 week of immobilization. Among the DDH children, who had never previously ambulated, there was no significant variation in the urinary calcium excretion. None of the serum parameters changed in either group throughout the study. Urinary stones were not evidenced by renal ultrasound. Therefore, the present data suggested that intermediate-term immobilization led to a transient increase in urinary calcium in 40% of LCP patients. Complications such as urinary stones were not observed. In conclusion, this modality of treatment does not impose an increased risk of urinary stone formation in LCP and DDH patients.}, }
@article {pmid16775454, year = {2006}, author = {Heilberg, IP and Weisinger, JR}, title = {Bone disease in idiopathic hypercalciuria.}, journal = {Current opinion in nephrology and hypertension}, volume = {15}, number = {4}, pages = {394-402}, doi = {10.1097/01.mnh.0000232880.58340.0c}, pmid = {16775454}, issn = {1062-4821}, mesh = {*Bone Density ; *Bone Diseases, Metabolic/etiology/metabolism/pathology/therapy ; Calcium/*metabolism ; Cytokines/metabolism ; Female ; *Fractures, Bone/etiology/metabolism/pathology/therapy ; Humans ; *Kidney Calculi/complications/metabolism/pathology/therapy ; Male ; Receptors, Calcitriol/metabolism ; }, abstract = {PURPOSE OF REVIEW: Decreased bone mineral density and increased prevalence of bone fractures have been found in patients with idiopathic hypercalciuria. The purpose of this review is to summarize the recent published evidence that supports a potential role of the bone, and its link to the kidney and intestine, in the pathogenesis of idiopathic hypercalciuria. The effects of hypercalciuria on bone and the implications for treatment are also reviewed.<br><br>RECENT FINDINGS: Evidence suggests that the incidence of a first fracture in kidney stone patients is fourfold higher than the control population. Support for the role of bone in the pathophysiology of hypercalciuria has been corroborated. New studies have detailed the effects of several cytokines - increased number and sensitivity of vitamin D receptors, and increased acid production - upon the bone acting cells. Similarly, recent clinical and experimental studies have suggested that genetic factors confer a predisposition to the formation of renal calcium stones and bone demineralization.<br><br>SUMMARY: Whether hypercalciuria is the result of a primary bone disorder, a consequence of a persisting negative calcium balance or a combination of both still remains to be determined. Nevertheless, bone status must be evaluated and followed up in patients with idiopathic hypercalciuria.}, }
@article {pmid16775452, year = {2006}, author = {Bai, S and Favus, MJ}, title = {Vitamin D and calcium receptors: links to hypercalciuria.}, journal = {Current opinion in nephrology and hypertension}, volume = {15}, number = {4}, pages = {381-385}, doi = {10.1097/01.mnh.0000232878.50716.26}, pmid = {16775452}, issn = {1062-4821}, support = {1P01 DK56788/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biological Transport/genetics ; Calcitriol/*metabolism ; Calcium Channels/deficiency/*metabolism ; Calcium Metabolism Disorders/genetics/*metabolism ; Epithelium/metabolism ; Humans ; Kidney/*metabolism ; Kidney Diseases/genetics/*metabolism ; Mice ; Mice, Knockout ; Rats ; Receptors, Calcium-Sensing/genetics/*metabolism ; TRPV Cation Channels/deficiency/*metabolism ; }, abstract = {PURPOSE OF REVIEW: In idiopathic hypercalciuria, patients have increased intestinal Ca absorption and decreased renal Ca reabsorption, with either elevated or normal serum levels of 1,25-dihydroxyvitamin D. As 1,25-dihydroxyvitamin D exerts its biologic effects through interactions with the vitamin D receptor, we examine the actions of this receptor and 1,25-dihydroxyvitamin D in animals with genetic hypercalciuria.<br><br>RECENT FINDINGS: In genetic hypercalciuric stone-forming rats intestinal calcium transport is increased and renal calcium reabsorption is reduced, yet serum 1,25-dihydroxyvitamin D levels are normal. Elevated intestinal and kidney vitamin D receptors suggest that increased tissue 1,25-dihydroxyvitamin D-vitamin D receptor complexes enhance 1,25-dihydroxyvitamin D actions on intestine and kidney, and vitamin D-dependent over-expression of renal calcium-sensing receptor alone can decrease tubule calcium reabsorption. In TRPV5-knockout mice, ablation of the renal calcium-influx channel decreases tubular calcium reabsorption, and secondary elevations in 1,25-dihydroxyvitamin D increase intestinal calcium transport.<br><br>SUMMARY: 1,25-Dihydroxyvitamin D or vitamin D receptor may change intestinal and renal epithelial calcium transport simultaneously or calcium-transport changes across renal epithelia may be primary with a vitamin D-mediated secondary increase in intestinal transport. The extent of homology between the animal models and human idiopathic hypercalciuria remains to be determined.}, }
@article {pmid16716792, year = {2006}, author = {Nicoletta, JA and Lande, MB}, title = {Medical evaluation and treatment of urolithiasis.}, journal = {Pediatric clinics of North America}, volume = {53}, number = {3}, pages = {479-91, vii}, doi = {10.1016/j.pcl.2006.03.001}, pmid = {16716792}, issn = {0031-3955}, support = {5 K23 HL080068-02/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Calcium Metabolism Disorders/complications/diagnosis/therapy/urine ; Child ; Child, Preschool ; Cystinuria/complications/diagnosis/therapy/urine ; Humans ; Hyperoxaluria/complications/diagnosis/therapy/urine ; Infant ; Infant, Newborn ; Metabolic Diseases/complications/diagnosis/therapy/urine ; Uric Acid/urine ; Urinalysis/methods ; Urinary Calculi/*diagnosis/etiology/*therapy ; }, abstract = {Nephrolithiasis is responsible for 1 in 1000 to 1 in 7600 pediatric hospital admissions annually throughout the United States. Seventy-five percent of children with nephrolithiasis have an identifiable predisposition to stone formation. This article reviews the different causes and disease states associated with nephrolithiasis in the pediatric population. The initial evaluation and the metabolic evaluation of children with nephrolithiasis are reviewed. Treatment modalities for the different stone types are also described.}, }
@article {pmid16611718, year = {2006}, author = {Hoopes, RR and Middleton, FA and Sen, S and Hueber, PA and Reid, R and Bushinsky, DA and Scheinman, SJ}, title = {Isolation and confirmation of a calcium excretion quantitative trait locus on chromosome 1 in genetic hypercalciuric stone-forming congenic rats.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {17}, number = {5}, pages = {1292-1304}, doi = {10.1681/ASN.2005080828}, pmid = {16611718}, issn = {1046-6673}, support = {R01 DK075462/DK/NIDDK NIH HHS/United States ; DK57716/DK/NIDDK NIH HHS/United States ; DK56788/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Animals, Congenic ; Calcium/*metabolism ; *Chromosome Mapping ; Genetic Predisposition to Disease/genetics ; Hypercalcemia/*genetics/*metabolism ; Kidney Calculi/*genetics/*metabolism ; Phenotype ; Quantitative Trait Loci/*genetics ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Hypercalciuria is the most common risk factor for kidney stones and has a substantial genetic component. The genetic hypercalciuric stone-forming (GHS) rat model displays complex changes in physiology involving intestine, bone, and kidney and overexpression of the vitamin D receptor, thereby reproducing the human phenotype of idiopathic hypercalciuria. Through quantitative trait locus (QTL) mapping of rats that were bred from GHS female rats and normocalciuric Wistar Kyoto (WKY) male rats, loci that are linked to hypercalciuria and account for a 6 to eight-fold phenotypic difference between the GHS and WKY progenitors were mapped. GHS x WKY rats were backcrossed to breed for congenic rats with the chromosome 1 QTL HC1 on a normocalciuric WKY background. Ten generations of backcrosses produced N10F1 rats, which were intercrossed to produce rats that were homozygous for GHS loci in the HC1 region between markers D1Mit2 and D1Mit32. On a high-calcium diet (1.2% calcium), significantly different levels of calcium excretion were found between male congenic (1.67 +/- 0.71 mg/24 h) and male WKY control rats (0.78 +/- 0.19 mg/24 h) and between female congenic (3.11 +/- 0.90 mg/24 h) and female WKY controls (2.11 +/- 0.50 mg/24 h); the congenics preserve the calcium excretion phenotype of the GHS parent strain. Microarray expression analyses of the congenic rats, compared with WKY rats, showed that of the top 100 most changed genes, twice as many as were statistically expected mapped to chromosome 1. Of these, there is a clear bias in gene expression change for genes in the region of the HC1. Of >1100 gene groups analyzed, one third of the 50 most differentially expressed gene groups have direct or secondary action on calcium metabolism or transport. This is the first QTL for hypercalciuria to be isolated in a congenic animal.}, }
@article {pmid16526260, year = {2005}, author = {Skodrić-Trifunović, V and Vucinić-Mihailović, V}, title = {[The role of vitamin D in the formation of granuloma and in calcium metabolism].}, journal = {Medicinski pregled}, volume = {58 Suppl 1}, number = {}, pages = {17-20}, pmid = {16526260}, issn = {0025-8105}, mesh = {Calcium/*metabolism ; Granuloma/etiology/*physiopathology ; Humans ; Kidney Calculi/metabolism ; Sarcoidosis/complications/metabolism/*physiopathology ; Vitamin D/*physiology ; }, abstract = {INTRODUCTION: Affection of the abdominal organs with sarcoidosis is a part of the generalized granulomatous diseases with clinical manifestations that vary depending on the affected organ.<br><br>Formation of granuloma represents a response of the host immune system to different antigen stimuli and it represents an attempt of the host to block the endogenous or exogenous irritant. The active form of vitamin D-1,25-dihydroxyvitamin-D (1,25-D) has an important function in formation of granuloma.<br><br>HEPATOMEGALY AND SPLENOMEGALY: As for the abdominal region, sarcoidosis is most frequently clinically manifested by liver and/or spleen enlargement (20-30% of the affected patients). However, granulomatous infiltrations may also be present along with normal sized organs. Other abdominal localizations are significantly less frequent.<br><br>Calcium metabolism disorder represents a significant problem in patients affected with sarcoidosis, particularly in extrapulmonary, chronic forms of the disease. It develops as a result of complex metabolic processes consequential to increased level of 1,25-D and it is considered to be a parameter of granuloma activity (physiological blood value is up to 45 pq/ml). An increased level of provitamin D initiates osteoclast activity that causes bone resorption, which represents a factor of osteoporosis that results in hypercalcemia and hypercalciuria.<br><br>Increased calcium release into blood results in production of calcium deposits in the soft tissues and certain organs and thus calculosis develops. It is clinically most frequently manifested as renal calculosis, which is approximately 20 times more frequent in patients affected with sarcoidosis in comparison to general population.<br><br>CONCLUSION: Examinations of abdominal organ involvement should be a standard procedure in each patient affected with sarcoidosis.}, }
@article {pmid16523966, year = {2006}, author = {Yamaguchi, S and Osanai, H}, title = {[Urinary stone disease indicating genetic background].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {64 Suppl 2}, number = {}, pages = {623-626}, pmid = {16523966}, issn = {0047-1852}, mesh = {Acidosis, Renal Tubular/genetics ; Amino Acids/metabolism ; Calcium/metabolism ; Carbohydrate Dehydrogenases/genetics ; Carrier Proteins/genetics ; Chloride Channels/genetics ; Cystinuria/genetics ; Humans ; Hyperoxaluria, Primary/genetics ; Hypoxanthine Phosphoribosyltransferase/deficiency ; Mutation ; Organic Anion Transporters/genetics ; Organic Cation Transport Proteins ; Oxalates/metabolism ; Proteinuria/genetics ; Proton-Translocating ATPases/genetics ; Purines/metabolism ; Transaminases/genetics ; Uric Acid/blood ; Urinary Calculi/*genetics ; }, }
@article {pmid16515769, year = {2006}, author = {Liebman, SE and Taylor, JG and Bushinsky, DA}, title = {Idiopathic hypercalciuria.}, journal = {Current rheumatology reports}, volume = {8}, number = {1}, pages = {70-75}, pmid = {16515769}, issn = {1523-3774}, support = {R01 DK075462/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bone and Bones/*metabolism ; Calcium/*metabolism/urine ; Humans ; Hypercalciuria/*complications/etiology/therapy ; Intestinal Mucosa/metabolism ; Kidney/metabolism ; Nephrolithiasis/*complications/etiology/therapy ; }, abstract = {Hypercalcuria is the most common metabolic disorder found in patients with nephrolithiasis. As the prevalence of kidney stones rises in industrialized nations, understanding the pathogenesis and treatment of hypercalciuria becomes increasingly important. Idiopathic hypercalciuria (IH), defined as an excess urine calcium excretion without an apparent underlying etiology, is the most frequent cause of hypercalciuria and will be the focus of this paper. Calcium homeostasis is tightly controlled and slight disturbances in transport at the level of the intestine, bone, and/or kidney can lead to excessive urine calcium excretion and promote stone formation. IH is a systemic disorder with dysregulation of calcium transport at a combination of these calcium regulatory sites. The goal of treatment is to prevent stone formation and relies on a combination of dietary and pharmaceutical interventions. Dietary management includes increasing fluid intake, salt restriction, animal protein restriction, and maintaining a normal calcium intake. Thiazide diuretics have proven effective in preventing calcium stone formation by reducing the urinary excretion of calcium. It is important to note that while decreasing urinary calcium excretion is important the clinician should focus primarily on reducing the supersaturation of calcium oxalate as this determines the true tendency for stone formation.}, }
@article {pmid16456694, year = {2006}, author = {Robertson, WG}, title = {Is prevention of stone recurrence financially worthwhile?.}, journal = {Urological research}, volume = {34}, number = {2}, pages = {157-161}, pmid = {16456694}, issn = {0300-5623}, mesh = {Calcium/metabolism ; Cellulose/analogs &amp; derivatives/metabolism/pharmacology ; *Disease Management ; Humans ; *Kidney Calculi/economics/prevention &amp; control/therapy ; Recurrence ; }, abstract = {This review shows that the cost of relying solely on minimally-invasive urological procedures for removing stones when patients return with recurrent stones is considerable and is significantly greater that that incurred by screening already proven recurrent stone-formers to identify the risk factors that are causing their stones and then instituting prophylactic measures to prevent stone recurrence. In the UK, at 1998 prices (when the original survey was carried out) for every stone episode prevented, there is a potential saving of almost 2,000 pound to the local Health Authority concerned. In spite of this, many Health Authorities have taken the liberty to discontinue comprehensive stone screening within the past 20 years under the mistaken supposition that minimally-invasive techniques for removing stones have "solved the stone problem". At UCLH in London where such a comprehensive scheme has been in place for the past 8 years, savings of up to 250,000 pound per year can be made by identifying the particular lifestyle as well as the epidemiological, metabolic and nutritional risk factors involved in a given patient and then instituting appropriate measures to prevent further stones.}, }
@article {pmid16452054, year = {2006}, author = {Osther, PJ}, title = {Effect of acute acid loading on acid-base and calcium metabolism.}, journal = {Scandinavian journal of urology and nephrology}, volume = {40}, number = {1}, pages = {35-44}, doi = {10.1080/00365590500368344}, pmid = {16452054}, issn = {0036-5599}, mesh = {*Acid-Base Equilibrium ; Administration, Oral ; Adult ; Ammonium Chloride/*administration &amp; dosage ; Calcium/*metabolism ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Follow-Up Studies ; Humans ; Hydrogen-Ion Concentration ; Kidney Calculi/*chemistry/*drug therapy ; Kidney Function Tests ; Male ; Middle Aged ; Phosphorus/*metabolism ; Probability ; Reference Values ; Risk Assessment ; Severity of Illness Index ; }, abstract = {OBJECTIVE: To investigate the acid-base and calcium metabolic responses to acute non-carbonic acid loading in idiopathic calcium stone-formers and healthy males using a quantitative organ physiological approach.<br><br>MATERIAL AND METHODS: Five-h ammonium chloride loading studies were performed in 12 male recurrent idiopathic calcium stone-formers and 12 matched healthy men using a randomized, placebo-controlled, cross-over design. Arterialized capillary blood, serum and urine were collected hourly for measurement of electrolytes, ionized calcium, magnesium, phosphate, parathyroid hormone and acid-base status. Concentrations of non-metabolizable base (NB) and acid (NA) were calculated from measured concentrations of non-metabolizable ions.<br><br>RESULTS: The extracellular acid-base status in the stone-formers during basal conditions and acid loading was comparable to the levels in the healthy controls. The stone-formers tended to have lower renal excretion rates of NA during acid loading; however, for a given degree of non-carbonic acidosis, controls and stone-formers excreted approximately the same amount of NA in the urine, suggesting that the capacity of tubular regeneration of NB was comparable in the two groups. Acid loading resulted in significantly increased concentrations of ionized calcium in serum in both controls and stone-formers. The increase in serum ionized calcium in response to acid loading was, however, significantly higher in the calcium stone-formers than in the healthy individuals. Acid loading resulted in massive calciuria in both groups, with significantly higher urinary calcium excretion rates in the stone-formers compared to the healthy subjects. Renal excretion rates of NA correlated significantly with renal calcium excretion rates in both groups. However, the stone-formers excreted significantly more calcium in the urine at a given rate of renal NA excretion.<br><br>CONCLUSIONS: The hypercalciuric and hypercalcaemic responses to loading with non-carbonic acid are more pronounced in recurrent idiopathic calcium stone-formers than in healthy individuals. Acid loading (i.e. protein ingestion) may contribute to disturbed bone metabolism in idiopathic calcium nephrolithiasis as well as calcium stone formation.}, }
@article {pmid16437224, year = {2006}, author = {Kavanagh, JP}, title = {Supersaturation and renal precipitation: the key to stone formation?.}, journal = {Urological research}, volume = {34}, number = {2}, pages = {81-85}, pmid = {16437224}, issn = {0300-5623}, mesh = {Animals ; Calcium/metabolism ; Chemical Precipitation ; Circadian Rhythm ; Humans ; Oxalates/metabolism ; Phosphates/metabolism ; Solubility ; Uric Acid/metabolism ; Urinary Calculi/chemistry/*etiology/metabolism ; }, }
@article {pmid16361942, year = {2006}, author = {Goracke-Postle, CJ and Nguyen, HO and Stone, LS and Fairbanks, CA}, title = {Release of tritiated agmatine from spinal synaptosomes.}, journal = {Neuroreport}, volume = {17}, number = {1}, pages = {13-17}, doi = {10.1097/01.wnr.0000192739.38653.aa}, pmid = {16361942}, issn = {0959-4965}, support = {K01 DA-00509/DA/NIDA NIH HHS/United States ; R21 DA-15387/DA/NIDA NIH HHS/United States ; T32DA007097/DA/NIDA NIH HHS/United States ; }, mesh = {Agmatine/*pharmacokinetics/pharmacology ; Analysis of Variance ; Animals ; Calcium/metabolism ; D-Aspartic Acid/pharmacokinetics ; Dose-Response Relationship, Drug ; Immunohistochemistry/methods ; Male ; Potassium Chloride/pharmacology ; Rats ; Spinal Cord/*cytology/drug effects ; Synaptophysin/metabolism ; Synaptosomes/drug effects/*metabolism ; Synaptotagmins/metabolism ; Temperature ; Time Factors ; Tritium/*pharmacokinetics ; }, abstract = {Intrathecal agmatine (decarboxylated arginine) moderates induction of neuropathic pain, spinal cord injury, and opioid tolerance in rodents. An endogenous central nervous system molecule and N-methyl-D-aspartate receptor antagonist/nitric oxide synthase inhibitor, agmatine may be a neuromodulator. We evaluated depolarization-induced release of agmatine from purified spinal nerve terminals (synaptosomes). Agmatine immunoreactivity was observed colocalized or closely apposed to some synaptophysin- and/or synaptotagmin-labeled structures. A temperature- and concentration-dependent uptake of [3H]-agmatine into synaptosomes was observed, consistent with an uptake mechanism. Potassium-induced depolarization resulted in release of [3H]-agmatine from the synaptosomes in a Ca2+-dependent manner, consistent with a neuromodulatory function. These results agree with previous reports of agmatine uptake into synaptosomes of the brain and extend those results to include stimulated release and a spinal site of activity.}, }
@article {pmid16164640, year = {2005}, author = {Borges, FT and Michelacci, YM and Aguiar, JA and Dalboni, MA and Garófalo, AS and Schor, N}, title = {Characterization of glycosaminoglycans in tubular epithelial cells: calcium oxalate and oxalate ions effects.}, journal = {Kidney international}, volume = {68}, number = {4}, pages = {1630-1642}, doi = {10.1111/j.1523-1755.2005.00577.x}, pmid = {16164640}, issn = {0085-2538}, mesh = {Animals ; Calcium/metabolism ; Calcium Oxalate/chemistry/*toxicity ; Cell Death/drug effects ; Cell Survival/drug effects ; Crystallization ; Dogs ; Durapatite/chemistry/toxicity ; Endocytosis ; Formates/chemistry/toxicity ; Glycosaminoglycans/biosynthesis/*metabolism ; Ionophores/pharmacology ; Ions/toxicity ; Kidney Tubules, Distal/cytology/drug effects/*metabolism ; Kidney Tubules, Proximal/cytology/drug effects/*metabolism ; LLC-PK1 Cells ; Necrosis ; Oxalates/chemistry/toxicity ; Sulfates/pharmacokinetics ; Sulfur Radioisotopes ; Swine ; Thapsigargin/pharmacology ; Urinary Calculi/chemistry/*metabolism/pathology ; }, abstract = {BACKGROUND: The interaction between tubular epithelial cells and calcium oxalate crystals or oxalate ions is a very precarious event in the lithogenesis. Urine contains ions, glycoproteins and glycosaminoglycans that inhibit the crystallization process and may protect the kidney against lithogenesis. We examined the effect of oxalate ions and calcium oxalate crystals upon the synthesis of glycosaminoglycans in distal [Madin-Darby canine kidney (MDCK)] and proximal (LLC-PK1) tubular cell lines.<br><br>METHODS: Glycosaminoglycan synthesis was analyzed by metabolic labeling with (35)S-sulfate and enzymatic digestion with specific mucopolysaccharidases. Cell death was assessed by fluorescent dyes and crystal endocytosis was analised by flow cytometry.<br><br>RESULTS: The main glycosaminoglycans synthesized by both cells were chondroitin sulfate and heparan sulfate most of them secreted to the culture medium or present at cellular surface. Exposition of MDCK cells to oxalate ions increased apoptosis rate and the incorporation of (35)S-sulfate in chondroitin sulfate and heparan sulfate, while calcium oxalate crystals were endocyted by LLC-PK1, induced necrotic cell death, and increased (35)S-sulfate incorporation in glycosaminoglycans. These effects seem to be specific and due to increased biosynthesis, since hydroxyapatite and other carboxylic acid did not induced cellular death or glycosaminoglycan synthesis and no changes in sulfation degree or molecular weight of glycosaminoglycans could be detected. Thapsigargin inhibited the glycosaminoglycan synthesis induced by calcium oxalate in LLC-PK1, suggesting that this effect was sensitive to the increase in cytosolic calcium.<br><br>CONCLUSION: Tubular cells may increase the synthesis of glycosaminoglycans to protect from the toxic insult of calcium oxalate crystals and oxalate ions, what could partially limit the lithogenesis.}, }
@article {pmid16123560, year = {2005}, author = {Baggio, B and Budakovic, A}, title = {Fatty acids and idiopathic calcium nephrolithiasis.}, journal = {Urologia internationalis}, volume = {75}, number = {2}, pages = {97-101}, doi = {10.1159/000087161}, pmid = {16123560}, issn = {0042-1138}, mesh = {Animals ; Calcium/urine ; Calcium Metabolism Disorders/*complications/diagnosis ; Disease Models, Animal ; Fatty Acids/*metabolism ; Humans ; Kidney Calculi/*etiology/*metabolism/physiopathology ; Risk Assessment ; Sensitivity and Specificity ; }, abstract = {Clinical and experimental investigations seem to underline the important role of fatty acids in the pathogenesis of hypercalciuria, a well-known risk factor for lithogenesis. To evaluate the relationships between the previously reported increase in plasma phospholipid arachidonic acid level and the factors responsible for calcium metabolism in idiopathic calcium nephrolithiasis, a best-fit model was constructed. This new statistical application shows a causal relationship between plasma phospholipid arachidonic acid content, intestinal calcium absorption, biochemical markers of bone turnover, urinary calcium excretion and bone mineral density at the lumbar spine. This model suggests that a defect in the phospholipid fatty acid composition could represent the primary event responsible for the mosaic of metabolic and clinical alterations that are distinctive features of renal stone formers, such as kidney, intestine, and bone calcium metabolism, and several forms of idiopathic hypercalciuria.}, }
@article {pmid16088653, year = {2002}, author = {Sharma, OP and Vucinić, V}, title = {Sarcoidosis of the thyroid and kidneys and calcium metabolism.}, journal = {Seminars in respiratory and critical care medicine}, volume = {23}, number = {6}, pages = {579-588}, doi = {10.1055/s-2002-36521}, pmid = {16088653}, issn = {1069-3424}, abstract = {In sarcoidosis, the thyroid and the kidneys are infrequently affected. Clinically recognizable thyroid involvement occurs in < 1% of sarcoidosis patients. Hyperthyroidism, myxodema, and thyroid occur with an equal frequency. It is important to distinguish sarcoidosis of the thyroid from other infections and disorders of the gland. Renal involvement may present as granulomatous infiltration of the renal parenchyma, glomerulonephritis, renal arteritis, and nephrocalcinosis or renal stones. The latter are due to abnormalities of calcium metabolism. Hypercalcemia occurs in about 10 to 13% of sarcoidosis patients; hypercalciuria is three times more frequent. Calcium abnormalities may precede, follow, or occur at any time during the course of sarcoidosis. An endogenous overproduction of 1,25-dihydroxyvitamin D [1,25-(OH (2))-D (3)] by granulomatous tissue and activated macrophages results in an increase of intestinal absorption of calcium. Corticosteriods, chloroquine, and hydroxychloroquine subdue 1,25-(OH (2))-D (3) production and correct hypercalcemia and hypercalciuria.}, }
@article {pmid16078084, year = {2005}, author = {Trinchieri, A}, title = {Bone mineral content in calcium renal stone formers.}, journal = {Urological research}, volume = {33}, number = {4}, pages = {247-253}, pmid = {16078084}, issn = {0300-5623}, mesh = {Animals ; *Bone Density ; Calcium/*metabolism ; Calcium, Dietary/administration &amp; dosage ; Dietary Proteins/administration &amp; dosage ; Humans ; Hyperparathyroidism/complications/metabolism ; Kidney Calculi/*metabolism ; Vitamin D/metabolism ; }, abstract = {Idiopathic renal calcium stone disease often presents with reduced bone mineral content. Investigations using non-invasive methods for the measurement of bone mineral content (single and dual-photon absorptiometry, dual-energy x-ray absorptiometry, quantitative computed tomodensitometry) show a slight decrease in skeletal mineral content of idiopathic renal stone formers (RSFs). The alterations in bone mineral content in RSFs have different explanations: prostaglandin-mediated bone resorption, subtle metabolic acidosis and 1-25 vitamin D disorders. Bone mineral content is worsened by insufficient dietary calcium leading to a negative calcium balance.}, }
@article {pmid16077235, year = {2005}, author = {Davidson, MT and Batchelar, DL and Velupillai, S and Denstedt, JD and Cunningham, IA}, title = {Laboratory coherent-scatter analysis of intact urinary stones with crystalline composition: a tomographic approach.}, journal = {Physics in medicine and biology}, volume = {50}, number = {16}, pages = {3907-3925}, doi = {10.1088/0031-9155/50/16/017}, pmid = {16077235}, issn = {0031-9155}, mesh = {Calcium/metabolism ; Calcium Oxalate/chemistry ; Humans ; Image Processing, Computer-Assisted ; Kidney Calculi/diagnostic imaging/*pathology ; Lithotripsy/methods ; Models, Statistical ; Models, Theoretical ; *Scattering, Radiation ; Spectrophotometry, Infrared ; Tomography, X-Ray Computed/*methods ; Urinary Calculi/diagnostic imaging/*pathology ; X-Rays ; }, abstract = {Knowledge of urinary stone composition and structure provides important insights in guiding treatment and preventing recurrence. No current method can successfully provide information relating structure and composition of intact stones. We are developing a tomographic technique that uses measures of coherently scattered diagnostic x-rays to yield stone composition. Coherent-scatter (CS) properties depend on molecular structure and are, therefore, sensitive to material composition. Powdered, amorphous or polycrystalline materials with no significant orientation produce circularly symmetric CS patterns. However, in materials with preferred crystallite orientation, like urinary stones, bright spots in CS patterns are observed. This compromises a composition analysis based on comparing CS measurements from calculi to a library of CS signatures from powdered chemicals. We show that a computed tomographic reconstruction of CS measurements using filtered backprojection (CSCT) effectively eliminates bright spots and yields CS patterns equivalent to powdered materials. This allows for direct comparison with a powdered chemical reference library to establish composition. Validation is achieved through a tomographic CS analysis of an aluminium (Al) rod phantom. Much like calculi, CS patterns from a solid polycrystalline Al rod exhibit diffraction spots, absent in the ring-like Al powder CS pattern. We show that the reconstructed Al CS cross-section is equivalent to its powdered counterpart and results in clearly defined composition images. The potential of CSCT to identify stone composition is demonstrated through images of intact stones deemed chemically pure by infrared spectroscopy. Computed tomographic reconstruction of CS signals allowed the generation of composition maps, showing the distribution of stone components. These images provide strong evidence that current laboratory techniques risk missing critical stone components due to inadequate sampling. This is of particular importance since follow-up treatments are based on these composition analyses. CS analysis can distinguish common stone components and can provide topographic composition maps of intact stones. Such details offer invaluable clinical information regarding stone formation, treatment and follow-up, and thus support the development of CS analysis as a laboratory stone analysis technique.}, }
@article {pmid16047226, year = {2005}, author = {Biyikli, NK and Alpay, H and Guran, T}, title = {Hypercalciuria and recurrent urinary tract infections: incidence and symptoms in children over 5 years of age.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {20}, number = {10}, pages = {1435-1438}, pmid = {16047226}, issn = {0931-041X}, mesh = {Age Distribution ; Calcium/*urine ; Calcium Metabolism Disorders/complications/*epidemiology/etiology/urine ; Child ; Creatinine/urine ; Female ; Humans ; Incidence ; Male ; Prospective Studies ; Recurrence ; Sex Distribution ; Turkey/epidemiology ; Urinary Calculi/complications/genetics ; Urinary Tract/abnormalities ; Urinary Tract Infections/complications/*epidemiology/etiology/urine ; }, abstract = {Hypercalciuria is an important and common risk factor in the formation of renal stones. In this study we evaluated the incidence and the clinical presentation of hypercalciuria in 75 children over 5 years of age with the diagnosis of recurrent urinary tract infection (UTI). We measured random urinary calcium/creatinine value (three times), 24-h urinary calcium excretion, serum calcium, phosphorus, electrolytes, blood gas, blood urea nitrogen and creatinine levels. Hypercalciuria was found in 32 patients (43%). The mean urinary calcium/creatinine ratio for hypercalciuric patients was 0.50+/-0.21 mg/mg (min: 0.24, max: 2.60). The mean urinary calcium/creatinine ratio for the rest of the study population--those without hypercalciuria--was 0.10+/-0.04 mg/mg (min: 0.01, max: 0.18). Presenting symptoms of the hypercalciuric patients and normocalciuric patients were similar. History of familial urolithiasis was positive in 19 patients (59%). Predisposing urinary tract abnormalities in recurrent UTI was shown in 12 of the hypercalciuric patients (12/32, 37.5%) and 8 of the normocalciuric patients (8/43, 19%) without a statistically significant difference between. We conclude that hypercalciuria is not a rare finding among recurrent UTI cases in Turkish children. Hypercalciuria does not modify the clinical presentation of UTI, and we suggest the investigation of urinary calcium excretion in children with recurrent UTI.}, }
@article {pmid16013013, year = {2005}, author = {Damasio, B and Massarino, F and Durand, F and Banchero, R and Bottino, P and De Franchis, V and Carmignani, G and Cannella, G}, title = {Prevalence of fasting hypercalciuria associated with increased citraturia in the ambulatory evaluation of nephrolithiasis.}, journal = {Journal of nephrology}, volume = {18}, number = {3}, pages = {262-266}, pmid = {16013013}, issn = {1121-8428}, mesh = {Calcium/*urine ; Calcium, Dietary/administration &amp; dosage ; Citrates/*urine ; Dose-Response Relationship, Drug ; Fasting/urine ; Female ; Follow-Up Studies ; Humans ; Kidney Calculi/diet therapy/epidemiology/*urine ; Male ; Middle Aged ; *Monitoring, Ambulatory ; *Outpatients ; Prevalence ; Recurrence ; Retrospective Studies ; }, abstract = {BACKGROUND: Nephrolithiasis is a common, high costing pathology of the urinary tract. The most common urinary abnormalities are fasting hypercalciuria, hypercalciuria and hypocitraturia. This study aimed to identify the principal urinary abnormalities in our patients.<br><br>METHODS: Ninety-eight patients (pts) (43 females, 55 males) with recurrent calcium nephrolithiasis underwent metabolic evaluation. In two 24-hr urine collections the following parameters were evaluated: calcium, phosphate, sodium, potassium, chloride, magnesium, citrate, oxalate, uric acid, creatinine (Cr), urea, ammonium and pH; blood measurement of calcium, phosphate, sodium, potassium, chloride, magnesium, uric acid, Cr, urea, acid-base balance ionized calcium and intact parathyroid hormone (iPTH) were also performed. A first morning voided urine sample was collected for measuring the urinary cross-links and fasting calciuria. The tubular threshold of phosphate (TmP) was calculated according to Walton and Bijovet. Metabolic evaluation was repeated in 63/98 pts after 7 days on a low calcium diet.<br><br>RESULTS: The most common urinary abnormalities were fasting hypercalciuria in 51/96 pts (53.1%), hypercalciuria in 33/97 pts (34%) and hypocitraturia in 29/98 pts (29%); 24/33 pts (73%) with hypercalciuria had fasting hypercalciuria. Hypercalciuria was partially corrected on the calcium-restricted diet, while fasting hypercalciuria was not. Urine citrate levels were significantly higher in patients with fasting hypercalciuria.<br><br>CONCLUSIONS: Fasting hypercalciuria was the most frequent urinary abnormality and it was not corrected with a calcium-restricted diet. In fasting hypercalciuric patients, increased bone resorption activity could be responsible for higher citraturia levels.}, }
@article {pmid23105553, year = {2005}, author = {Rao, TV and Choudhary, VK}, title = {Effect of pyridoxine (Vitamin-B(6)) supplementation on calciuria and oxaluria levels of some normal healthy persons and urinary stone patients.}, journal = {Indian journal of clinical biochemistry : IJCB}, volume = {20}, number = {2}, pages = {166-169}, pmid = {23105553}, issn = {0970-1915}, abstract = {Effect of pyridoxine (Vitamin-B(6)) supplementation on calciuria and oxaluria levels of 20 normal healthy persons and 17 urinary stone patients has been studied. Mean 24 hr urinary calcium and oxalate levels of controls (healthy persons) and stone patients were estimated in presupplementation period and at every 20 days interval during supplementation. Stone patients were divided into two groups viz., mild hyperoxaluriacs and moderate hyperoxaluriacs, based on their pre-supplementation (base line) oxaluria levels. 60 days of pyridoxine supplementation, at the rate of 10 mg/day, resulted in a significant decrease (p<0.01 for mild hyperoxaluriacs and p<0.001 for moderate hyperoxaluriacs) in mean 24 hr urinary oxalate levels of urinary stone patients. The corresponding decrement in mean oxaluria level of controls was, however, only mild. The decrease of mean calciuria level of controls as well as stone patients, upon pyridoxine supplementation, were also found to be only mild and not significant. Utility of pyridoxine therapy in oxalate urolithiasis has been discussed in the light of results.}, }
@article {pmid15948718, year = {2005}, author = {Tsuji, H and Umekawa, T and Kurita, T and Uemura, H and Iguchi, M and Kin, K and Kushida, K}, title = {Analysis of bone mineral density in urolithiasis patients.}, journal = {International journal of urology : official journal of the Japanese Urological Association}, volume = {12}, number = {4}, pages = {335-339}, doi = {10.1111/j.1442-2042.2005.01049.x}, pmid = {15948718}, issn = {0919-8172}, mesh = {Absorptiometry, Photon ; Adult ; Age Factors ; *Bone Density ; Calcium/urine ; Female ; Humans ; Incidence ; Kidney Calculi/epidemiology/*metabolism ; Lumbar Vertebrae/diagnostic imaging ; Male ; Middle Aged ; Risk Factors ; Sex Factors ; }, abstract = {BACKGROUND: The association between hypercalciuria and bone mineral density (BMD) has been already recognized. The aim of the present study is to relate BMD to age and sex and to evaluate the calcium metabolism and hypercalciuria-defined dietary or non-dietary category in patients with urolithiasis.<br><br>METHODS: The BMI of the L2-L4 lumbar vertebrae was measured in 310 renal stone patients (191 men and 119 women). Percent age matched score (%AMS), which is the percent ratio of measured BMD to the mean BMD of age-matched control subjects, was utilized for the appraisal of BMD. Low BMD groups were defined by lower than 90% of %AMS.<br><br>RESULTS: Low BMD was observed in 27.7% of urinary stone patients, which was not a significant difference to that of control subjects (23.5%) who were measured in the health examination. In male patients with urolithiasis, the frequency of patients in whom BMD had been apt to decrease since youth was high, but there was not a proven significant difference among the three age groups (20-39 years old, 40-59 years old and 60 years old or older). In contrast, for female stone patients, the frequency of low BMD markedly increased in patients aged 40 years or older, when menopause occurs. Furthermore, in female stone patients with hypercalciuria, the frequency of reduced BMD reached more than 40%. When the cause was non-dietary hypercalciuria (classified mainly on the daily amount of urinary calcium excretion after ingestion of calculus test diet), the frequency of reduced BMD reached 65% (P < 0.01).<br><br>CONCLUSIONS: In case female stone patients with non-dietary hypercalciuria become menopausal, not only the risk of recurrent lithiasis increases, but the possibility of developing osteopenia in the future also increases. Appropriate treatments for prophylactic effects on urolithiasis or osteopenia should be considered, as judged from BMD, diet, sex, urinary calcium excretion and other factors synthetically.}, }
@article {pmid15944517, year = {2005}, author = {Chandhoke, PS}, title = {Metabolic abnormalities and the medical management of calcium oxalate nephrolithiasis.}, journal = {Minerva urologica e nefrologica = The Italian journal of urology and nephrology}, volume = {57}, number = {1}, pages = {9-16}, pmid = {15944517}, issn = {0393-2249}, mesh = {Calcium Metabolism Disorders/complications/urine ; Calcium Oxalate/*metabolism ; Humans ; Kidney Calculi/etiology/*metabolism/therapy ; }, abstract = {The lifetime prevalence of urolithiasis is approximately 12% for men and 7% for women in the United States and seems to be increasing; the cost of managing kidney stones continues to escalate. The most common kidney stones continue to be composed primarily of calcium and are an admixture of phosphate and oxalate. Of these, calcium oxalate stones are the most predominant. This review will focus only on the pathogenesis and medical management of calcium oxalate stones.}, }
@article {pmid15917184, year = {2005}, author = {Meimaridou, E and Jacobson, J and Seddon, AM and Noronha-Dutra, AA and Robertson, WG and Hothersall, JS}, title = {Crystal and microparticle effects on MDCK cell superoxide production: oxalate-specific mitochondrial membrane potential changes.}, journal = {Free radical biology &amp; medicine}, volume = {38}, number = {12}, pages = {1553-1564}, doi = {10.1016/j.freeradbiomed.2005.02.020}, pmid = {15917184}, issn = {0891-5849}, mesh = {Animals ; Calcium/metabolism ; Calcium Oxalate/*pharmacology ; Calcium Phosphates/pharmacology ; Cell Line ; Crystallization ; Dicyclohexylcarbodiimide/pharmacology ; Dogs ; Durapatite/pharmacology ; Intracellular Membranes/*drug effects ; Ion Channels/drug effects ; Kidney/*metabolism ; Membrane Potentials/*drug effects ; Microscopy, Electron, Scanning ; Mitochondria/drug effects/ultrastructure ; Nigericin/pharmacology ; Potassium-Hydrogen Antiporters/antagonists &amp; inhibitors ; Superoxides/*metabolism ; }, abstract = {We have previously shown that crystals of calcium oxalate (COM) elicit a superoxide (O2-) response from mitochondria. We have now investigated: (i) if other microparticles can elicit the same response, (ii) if processing of crystals is involved, and (iii) at what level of mitochondrial function oxalate acts. O2- was measured in digitonin-permeabilized MDCK cells by lucigenin (10 microM) chemiluminescence. [(14)C]-COM dissociation was examined with or without EDTA and employing alternative chelators. Whereas mitochondrial O2- in COM-treated cells was three- to fourfold enhanced compared to controls, other particulates (uric acid, zymosan, and latex beads) either did not increase O2- or were much less effective (hydroxyapatite +50%, p < 0.01), with all at 28 microg/cm(2). Free oxalate (750 microM), at the level released from COM with EDTA (1 mM), increased O2- (+50%, p < 0.01). Omitting EDTA abrogated this signal, which was restored completely by EGTA and partially by ascorbate, but not by desferrioxamine or citrate. Omission of phosphate abrogated O2-, implicating phosphate-dependent mitochondrial dicarboxylate transport. COM caused a time-related increase in the mitochondrial membrane potential (deltapsi(m)) measured using TMRM fluorescence and confocal microscopy. Application of COM to Fura 2-loaded cells induced rapid, large-amplitude cytosolic Ca(2+) transients, which were inhibited by thapsigargin, indicating that COM induces release of Ca(2+) from internal stores. Thus, COM-induced mitochondrial O2- requires the release of free oxalate and contributes to a synergistic response. Intracellular dissociation of COM and the mitochondrial dicarboxylate transporter are important in O2- production, which is probably regulated by deltapsi(m).}, }
@article {pmid15899849, year = {2005}, author = {Roose, JP and Mollenauer, M and Gupta, VA and Stone, J and Weiss, A}, title = {A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells.}, journal = {Molecular and cellular biology}, volume = {25}, number = {11}, pages = {4426-4441}, pmid = {15899849}, issn = {0270-7306}, support = {R01 CA072531/CA/NCI NIH HHS/United States ; }, mesh = {Acetophenones/pharmacology ; Antigens, CD/metabolism ; Antigens, Differentiation, T-Lymphocyte/metabolism ; Benzopyrans/pharmacology ; Calcium/metabolism ; DNA-Binding Proteins/deficiency/genetics/*metabolism ; Diglycerides/*metabolism ; Enzyme Activation ; Guanine Nucleotide Exchange Factors/deficiency/genetics/*metabolism ; Humans ; Isoenzymes/antagonists &amp; inhibitors/*metabolism ; Jurkat Cells ; Lectins, C-Type ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Phosphorylation ; Protein Kinase C/antagonists &amp; inhibitors/*metabolism ; Protein Kinase C-theta ; Protein Kinase Inhibitors/pharmacology ; RNA Interference ; Receptors, Antigen, T-Cell, alpha-beta/*metabolism ; Signal Transduction ; T-Lymphocytes/drug effects/*enzymology/immunology ; Tetradecanoylphorbol Acetate/pharmacology ; ras GTPase-Activating Proteins/genetics/metabolism ; ras Proteins/*metabolism ; }, abstract = {Ras GTPases are on/off switches regulating numerous cellular responses by signaling to various effector molecules. In T lymphocytes, Ras can be activated by two Ras exchange factors, SOS and RasGRP1, which are recruited through the adapters Grb2 and LAT and via the second-messenger diacylglycerol (DAG), respectively. Mitogen-activated protein (MAP) kinase phosphorylation patterns induced by active Ras can vary and contribute to distinct cellular responses. The different consequences of Ras activation by either guanine exchange factor are unknown. DAG also recruits and activates the kinase protein kinase Ctheta (PKCtheta) turning on the Erk MAP kinase pathway, but the biochemical mechanism responsible is unclear. We generated T-cell clones deficient in phorbol myristate acetate (a surrogate for DAG)-induced Ras activation. Analysis of a RasGRP1-deficient Jurkat T-cell clone and RasGRP1 RNA interference in wild-type cells revealed that RasGRP1 is required for optimal, antigen receptor-triggered Ras-Erk activation. RasGRP1 relies on its DAG-binding domain to selectively activate Erk kinases. Activation of Erk correlates with the phosphorylation of threonine residue 184 in RasGRP1. This phosphorylation event requires the activities of novel PKC kinases. Conversely, active PKCtheta depends on RasGRP1 sufficiency to effectively trigger downstream events. Last, DAG-PKC-RasGRP1-driven Ras-Erk activation in T cells is a unique signaling event, not simply compensated for by SOS activity.}, }
@article {pmid15857904, year = {2005}, author = {Reigada, D and Lu, W and Zhang, X and Friedman, C and Pendrak, K and McGlinn, A and Stone, RA and Laties, AM and Mitchell, CH}, title = {Degradation of extracellular ATP by the retinal pigment epithelium.}, journal = {American journal of physiology. Cell physiology}, volume = {289}, number = {3}, pages = {C617-24}, doi = {10.1152/ajpcell.00542.2004}, pmid = {15857904}, issn = {0363-6143}, support = {EY-001583/EY/NEI NIH HHS/United States ; EY-07354/EY/NEI NIH HHS/United States ; R01 EY-013434/EY/NEI NIH HHS/United States ; EY-10009/EY/NEI NIH HHS/United States ; R01 EY013434-04/EY/NEI NIH HHS/United States ; }, mesh = {Adenosine Diphosphate/pharmacology ; Adenosine Triphosphatases/antagonists &amp; inhibitors/genetics/*metabolism ; Adenosine Triphosphate/*pharmacokinetics ; Animals ; Antigens, CD/genetics/metabolism ; Apyrase/antagonists &amp; inhibitors/genetics/metabolism ; Calcium/metabolism ; Calcium Signaling/physiology ; Cattle ; Cell Line ; Enzyme Inhibitors/pharmacology ; Extracellular Space/metabolism ; Gene Expression Regulation, Enzymologic ; Glucose-6-Phosphate Isomerase/antagonists &amp; inhibitors/genetics/metabolism ; Glycoproteins/antagonists &amp; inhibitors/genetics/metabolism ; Humans ; Membrane Proteins/metabolism ; Multienzyme Complexes/antagonists &amp; inhibitors/genetics/metabolism ; Phosphodiesterase I ; Phosphoric Diester Hydrolases/genetics/*metabolism ; Pigment Epithelium of Eye/cytology/*enzymology ; Purines/metabolism ; Pyrophosphatases/antagonists &amp; inhibitors/genetics/*metabolism ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2Y1 ; Receptors, Purinergic P2Y12 ; Reverse Transcriptase Polymerase Chain Reaction ; }, abstract = {Stimulation of ATP or adenosine receptors causes important physiological changes in retinal pigment epithelial (RPE) cells that may influence their relationship to the adjacent photoreceptors. While RPE cells have been shown to release ATP, the regulation of extracellular ATP levels and the production of dephosphorylated purines is not clear. This study examined the degradation of ATP by RPE cells and the physiological effects of the adenosine diphosphate (ADP) that result. ATP was readily broken down by both cultured human ARPE-19 cells and the apical membrane of fresh bovine RPE cells. The compounds ARL67156 and betagamma-mATP inhibited this degradation in both cell types. RT-PCR analysis of ARPE-19 cells found mRNA message for multiple extracellular degradative enzymes; ectonucleotide pyrophosphatase/phosphodiesterase eNPP1, eNPP2, and eNPP3; the ectoATPase ectonucleoside triphosphate diphosphohydrolase NTPDase2, NTPDase3, and some message for NTPDase1. Considerable levels of ADP bathed RPE cells, consistent with a role for NTPDase2. ADP and ATP increased levels of intracellular Ca(2+). Both responses were inhibited by thapsigargin and P2Y(1) receptor inhibitor MRS 2179. Message for both P2Y(1) and P2Y(12) receptors was detected in ARPE-19 cells. These results suggest that extracellular degradation of ATP in subretinal space can result in the production of ADP. This ADP can stimulate P2Y receptors and augment Ca(2+) signaling in the RPE.}, }
@article {pmid15844385, year = {2005}, author = {Srivastava, T and Alon, US}, title = {Urolithiasis in adolescent children.}, journal = {Adolescent medicine clinics}, volume = {16}, number = {1}, pages = {87-109}, doi = {10.1016/j.admecli.2004.10.003}, pmid = {15844385}, issn = {1547-3368}, mesh = {Adolescent ; Calcium/metabolism ; Cystinuria/physiopathology/therapy ; Food ; Humans ; Uric Acid/blood/urine ; Urinary Calculi/*diagnosis/physiopathology/prevention &amp; control/surgery ; Xanthine/urine ; }, abstract = {Idiopathic urolithiasis in children has become more frequent in the past few decades as a result of increasing affluence and rapid change in our society's dietary habits. In Western societies, calcium stones in the kidney and ureter predominate. Pediatric urolithiases, unlike the adult form, require a comprehensive metabolic evaluation, because metabolic and enzymatic derangements play an important role in their pathogenesis. The recent advancements in endoscopic procedures, interventional radiology, and lithotripsy have allowed children to be managed effectively without open surgery. Pediatric urolithiasis requires a close working relationship between the urologist for acute surgical management of urolithiasis and the nephrologists for prevention of stone formation. In many children and adolescents with urolithiasis, a nonpharmacologic approach involving the adoption of healthy nutrition habits may suffice.}, }
@article {pmid15840731, year = {2005}, author = {Ceylan, K and Topal, C and Erkoc, R and Sayarlioglu, H and Can, S and Yilmaz, Y and Dogan, E and Algun, E and Gonulalan, H}, title = {Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease.}, journal = {The Annals of pharmacotherapy}, volume = {39}, number = {6}, pages = {1034-1038}, doi = {10.1345/aph.1E544}, pmid = {15840731}, issn = {1060-0280}, mesh = {Adult ; Antihypertensive Agents/adverse effects/therapeutic use ; Blood Pressure/drug effects ; Calcium/blood/*urine ; Calcium Metabolism Disorders/urine ; Creatinine/urine ; Delayed-Action Preparations ; Dizziness/chemically induced ; Female ; Humans ; Hypertension/drug therapy/physiopathology/urine ; Indapamide/adverse effects/*therapeutic use ; Male ; Middle Aged ; Patient Selection ; Potassium/blood ; Tinnitus/chemically induced ; Treatment Outcome ; Triglycerides/blood ; Uric Acid/blood ; Urinary Calculi/diagnosis/*drug therapy/urine ; }, abstract = {BACKGROUND: Indapamide is an antihypertensive agent similar to thiazides, but with some different effects. Thiazide and thiazide-like diuretics are useful in preventing recurrent urinary stone formation due to their hypocalciuric effects.<br><br>OBJECTIVE: To determine the hypocalciuric and other effects on certain laboratory parameters of indapamide 1.5 mg in different patient groups.<br><br>METHODS: Four groups of patients recruited from urology and nephrology outpatient departments were experiencing non-hypercalciuric urinary stone disease (group 1), idiopathic hypercalciuria (group 2), urinary stone disease with hypercalciuria (group 3), and essential hypertension (group 4). In all patients, fasting serum uric acid, calcium, sodium, potassium, cholesterol, triglyceride, parathyroid hormone (PTH) values, and morning second-spot urine calcium and creatinine levels were assessed before and 8 weeks after treatment with indapamide.<br><br>RESULTS: Urinary calcium excretion was reduced significantly in all groups: group 1 from 0.10 +/- 0.02 to 0.07 +/- 0.03 (mean +/-SD; 30% reduction; p < 0.001), group 2 from 0.30 +/- 0.15 to 0.15 +/- 0.10 (50% reduction; p < 0.001), group 3 from 0.35 +/- 0.15 to 0.20 +/- 0.10 (43% reduction; p < 0.001), and group 4 from 0.10 +/- 0.03 to 0.08 +/- 0.02 (20% reduction; p < 0.0010). These results should be interpreted with caution since no control group was included in this study. Mean serum uric acid and triglyceride levels were significantly increased, and mean PTH and potassium levels and diastolic and systolic blood pressure were significantly decreased in all groups. Few temporary adverse effects, such as dizziness and fatigue, were noticed and none of them caused discontinuation of treatment.<br><br>CONCLUSIONS: Indapamide 1.5 mg/day is effective in decreasing calciuria in patients with non-hypercalciuric urinary stone disease, idiopathic hypercalciuria, urinary stone disease with hypercalciuria, and essential hypertension. This could be achieved with few adverse effects similar to those of thiazides and indapamide 2.5 mg. Indapamide decreased the PTH levels in all groups. Long-term clinical benefits of these effects should be evaluated prospectively with further randomized studies.}, }
@article {pmid15826946, year = {2005}, author = {Blumenschein, TM and Stone, DB and Fletterick, RJ and Mendelson, RA and Sykes, BD}, title = {Calcium-dependent changes in the flexibility of the regulatory domain of troponin C in the troponin complex.}, journal = {The Journal of biological chemistry}, volume = {280}, number = {23}, pages = {21924-21932}, doi = {10.1074/jbc.M500574200}, pmid = {15826946}, issn = {0021-9258}, support = {AR 45659/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Anisotropy ; Calcium/*metabolism ; Chickens ; Crystallography, X-Ray ; Egtazic Acid/chemistry ; Escherichia coli/metabolism ; Magnesium/chemistry ; Magnetic Resonance Spectroscopy ; Models, Statistical ; Muscle, Skeletal/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Time Factors ; Troponin/chemistry ; Troponin C/*chemistry/metabolism ; }, abstract = {With the recent advances in structure determination of the troponin complex, it becomes even more important to understand the dynamics of its components and how they are affected by the presence or absence of Ca(2+). We used NMR techniques to study the backbone dynamics of skeletal troponin C (TnC) in the complex. Transverse relaxation-optimized spectroscopy pulse sequences and deuteration of TnC were essential to assign most of the TnC residues in the complex. Backbone amide (15)N relaxation times were measured in the presence of Ca(2+) or EGTA/Mg(2+). T(1) relaxation times could not be interpreted precisely, because for a molecule of this size, the longitudinal backbone amide (15)N relaxation rate due to chemical shift anisotropy and dipole-dipole interactions becomes too small, and other relaxation mechanisms become relevant. T(2) relaxation times were of the expected magnitude for a complex of this size, and most of the variation of T(2) times in the presence of Ca(2+) could be explained by the anisotropy of the complex, suggesting a relatively rigid molecule. The only exception was EF-hand site III and helix F immediately after, which are more flexible than the rest of the molecule. In the presence of EGTA/Mg(2+), relaxation times for residues in the C-domain of TnC are very similar to values in the presence of Ca(2+), whereas the N-domain becomes more flexible. Taken together with the high flexibility of the linker between the two domains, we concluded that in the absence of Ca(2+), the N-domain of TnC moves independently from the rest of the complex.}, }
@article {pmid15812202, year = {2005}, author = {Dal Moro, F and Mancini, M and Tavolini, IM and De Marco, V and Bassi, P}, title = {Cellular and molecular gateways to urolithiasis: a new insight.}, journal = {Urologia internationalis}, volume = {74}, number = {3}, pages = {193-197}, doi = {10.1159/000083547}, pmid = {15812202}, issn = {0042-1138}, mesh = {Animals ; *Apoptosis ; Biological Transport, Active/*physiology ; Calcium/metabolism ; Crystallization ; Cysteine/metabolism ; Humans ; Magnesium Compounds/metabolism ; Phosphates/metabolism ; Struvite ; Uric Acid/metabolism ; Urinary Calculi/*metabolism/*pathology ; }, abstract = {Urolithiasis is a relevant clinical problem in everyday practice with a subsequent burden for the health system. Urolithiasis is classically explained as the derangement in the process of biomineralization involving the equilibrium between promoters and inhibitors of crystallization: a deficit of one or several inhibitors or an excess of one or several promoters plays a pivotal role in the stone formation. The revolutionary introduction of the molecular biology in medicine has given a new insight in urolithiasis too. Genetic factors have also been postulated to play an important role. A review of the current knowledge on urolithiasis based upon a molecular and genetic approach is reported.}, }
@article {pmid15794272, year = {2004}, author = {Kwapuliński, J and Ahnert, B and Bogunia, M and Bogunia, E and Nogaj, E and Kowol, J and Rutkiewicz, J}, title = {[Analysis of possible interaction between lead and calcium in gallstones from active and passive smoking and no smoking women].}, journal = {Przeglad lekarski}, volume = {61}, number = {10}, pages = {1135-1139}, pmid = {15794272}, issn = {0033-2240}, mesh = {Calcium/*metabolism ; Case-Control Studies ; Cholelithiasis/metabolism ; Female ; Gallstones/*metabolism ; Humans ; Lead/*metabolism ; Poland ; Smoking/*adverse effects ; Spectrophotometry, Atomic ; Tobacco Smoke Pollution/*adverse effects ; }, abstract = {The problem of interaction between lead and calcium in gallstones from active and passive smoking and no smoking women living in southern Poland is presented in the work. The subject of the research were gallstones, gained intraoperatively from 93 women (24 active smoking, 18 passive smoking, 51 no smoking women). The content of lead and calcium was determined using atomic emission spectroscopy with inductive couple plasma (ICP-AES). The place of living, smoking and age play an important role in changing the lead and calcium content of gallstones.}, }
@article {pmid15784741, year = {2005}, author = {Vinogradova, MV and Stone, DB and Malanina, GG and Karatzaferi, C and Cooke, R and Mendelson, RA and Fletterick, RJ}, title = {Ca(2+)-regulated structural changes in troponin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {102}, number = {14}, pages = {5038-5043}, pmid = {15784741}, issn = {0027-8424}, support = {R01AR45659/AR/NIAMS NIH HHS/United States ; R01 AR045659/AR/NIAMS NIH HHS/United States ; P01AR42895/AR/NIAMS NIH HHS/United States ; R01 GM067830/GM/NIGMS NIH HHS/United States ; R01GM067830/GM/NIGMS NIH HHS/United States ; P01 AR042895/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Biophysical Phenomena ; Biophysics ; Calcium/*metabolism ; Chickens ; Crystallography, X-Ray ; Detergents ; In Vitro Techniques ; Models, Biological ; Models, Molecular ; Multiprotein Complexes ; Muscle Contraction/physiology ; Muscle, Skeletal/metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Conformation ; Recombinant Proteins/chemistry/metabolism ; Troponin C/*chemistry/*metabolism ; Troponin T/*chemistry/*metabolism ; }, abstract = {Troponin senses Ca2+ to regulate contraction in striated muscle. Structures of skeletal muscle troponin composed of TnC (the sensor), TnI (the regulator), and TnT (the link to the muscle thin filament) have been determined. The structure of troponin in the Ca(2+)-activated state features a nearly twofold symmetrical assembly of TnI and TnT subunits penetrated asymmetrically by the dumbbell-shaped TnC subunit. Ca ions are thought to regulate contraction by controlling the presentation to and withdrawal of the TnI inhibitory segment from the thin filament. Here, we show that the rigid central helix of the sensor binds the inhibitory segment of TnI in the Ca(2+)-activated state. Comparison of crystal structures of troponin in the Ca(2+)-activated state at 3.0 angstroms resolution and in the Ca(2+)-free state at 7.0 angstroms resolution shows that the long framework helices of TnI and TnT, presumed to be a Ca(2+)-independent structural domain of troponin are unchanged. Loss of Ca ions causes the rigid central helix of the sensor to collapse and to release the inhibitory segment of TnI. The inhibitory segment of TnI changes conformation from an extended loop in the presence of Ca2+ to a short alpha-helix in its absence. We also show that Anapoe, a detergent molecule, increases the contractile force of muscle fibers and binds specifically, together with the TnI switch helix, in a hydrophobic pocket of TnC upon activation by Ca ions.}, }
@article {pmid15783122, year = {2004}, author = {Yatzidis, H}, title = {Gestational urinary hyperthiosulfaturia protects hypercalciuric normal pregnant women from nephrolithiasis.}, journal = {International urology and nephrology}, volume = {36}, number = {3}, pages = {445-449}, pmid = {15783122}, issn = {0301-1623}, mesh = {Adult ; Calcium Metabolism Disorders/*urine ; Female ; Humans ; *Kidney Calculi ; Pregnancy ; Pregnancy Complications/*urine ; Thiosulfates/*urine ; }, abstract = {Urinary calcium excretion increases by 1-2-fold during gestation in normal, uncomplicated pregnant women. Hypercalciuria occurs in all trimesters and elevates urine supersaturation with regards to calcium oxalate. However, crystalluria has not been a frequent clinical finding and stone formation is not a common complication of pregnancy. To elucidate this discrepancy we measured various chemical entities (i.e. calcium, oxalate, uric acid, phosphorous, magnesium, citrate, sulfate and thiosulfate) in urine at the end of each trimester of 25 pregnant women. Twenty-five healthy women served as controls. Our observations show that endogenous thiosulfate, a natural component of urine, increased considerably during pregnancy to approximately 36, 38 and 40 microM/24 hour at the end of each three trimesters. One month after delivery, endogenous thiosulfaturia and hypercalciuria, in parallel, returned to initial normal values. Consequently, it seems that gestational hyperthiosulfaturia protects hypercalciuric normal pregnant women from the risk of nephrolithiasis.}, }
@article {pmid15781479, year = {2005}, author = {Watts, RW}, title = {Idiopathic urinary stone disease: possible polygenic aetiological factors.}, journal = {QJM : monthly journal of the Association of Physicians}, volume = {98}, number = {4}, pages = {241-246}, doi = {10.1093/qjmed/hci041}, pmid = {15781479}, issn = {1460-2725}, mesh = {Calcium/metabolism ; Calcium Oxalate/antagonists &amp; inhibitors/metabolism ; Female ; Genetic Diseases, X-Linked/genetics/metabolism ; Glycoproteins/metabolism ; Glycosaminoglycans/metabolism ; Humans ; Male ; Membrane Glycoproteins/metabolism ; Mucoproteins/metabolism ; Osteopontin ; Peptide Fragments/metabolism ; Protein Precursors/metabolism ; Prothrombin/metabolism ; Receptors, Calcium-Sensing/metabolism ; Serine Proteinase Inhibitors/metabolism ; Sialoglycoproteins/metabolism ; Trypsin Inhibitor, Kunitz Soybean/metabolism ; Urinary Calculi/*genetics/metabolism ; Uromodulin ; Vitamin D/biosynthesis ; }, }
@article {pmid15780505, year = {2005}, author = {McCarty, MF}, title = {Marinobufagenin may mediate the adverse impact of salty diets on renal calcium retention by impairing the efficiency of renal tubular sodium-calcium exchange.}, journal = {Medical hypotheses}, volume = {64}, number = {5}, pages = {1027-1029}, doi = {10.1016/j.mehy.2003.10.033}, pmid = {15780505}, issn = {0306-9877}, mesh = {Bufanolides/*pharmacology ; Calcium/*metabolism ; Humans ; Ion Transport ; Kidney Tubules/*drug effects/metabolism ; Sodium/*metabolism ; Sodium Chloride, Dietary/*adverse effects/*antagonists &amp; inhibitors ; }, abstract = {For reasons yet to be clarified, salt loading and plasma volume expansion decrease renal calcium retention; consequently, high-salt diets are thought to increase risk for osteoporosis and renal stones. These measures also can evoke increased adrenal production of the natriuretic factor marinobufagenin (MBG), recently implicated in the genesis of essential hypertension. MBG achieves natriuresis via potent selective inhibition of the alpha-1-type sodium pump, expressed throughout the nephron. In as much as renal calcium retention is largely dependent on efficient activity of calcium-sodium exchangers situated in the basolateral membranes of tubular epithelium, it is evident that an increased intracellular sodium concentration consequent to sodium pump inhibition could blunt the activity of these exchangers. Thus, it is postulated that MBG mediates the impact of salt loading on renal calcium retention.}, }
@article {pmid15764255, year = {2004}, author = {Escribano, J and Balaguer, A and Martin, R and Feliu, A and Espax, R}, title = {Childhood idiopathic hypercalciuria--clinical significance of renal calyceal microlithiasis and risk of calcium nephrolithiasis.}, journal = {Scandinavian journal of urology and nephrology}, volume = {38}, number = {5}, pages = {422-426}, doi = {10.1080/00365590410033434}, pmid = {15764255}, issn = {0036-5599}, mesh = {Adolescent ; Age Distribution ; Calcium/*urine ; Calcium Metabolism Disorders/*diagnosis/epidemiology ; Child ; Child, Preschool ; Cohort Studies ; Female ; Hematuria/diagnosis/epidemiology ; Humans ; Incidence ; Male ; Nephrocalcinosis/*diagnostic imaging/epidemiology/physiopathology ; Prognosis ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index ; Sex Distribution ; Ultrasonography ; }, abstract = {OBJECTIVE: To evaluate the clinical significance of renal calyceal microlithiasis (RCM) in children with idiopathic hypercalciuria (IHC).<br><br>MATERIAL AND METHODS: RCM is a renal echographic finding defined as the presence of hyperechogenic spots < 3 mm in diameter in the renal calyces. These spots have been associated with the presence of nephrourological symptoms in children and are considered to represent a stage prior to urolithiasis. We reviewed the medical records of 103 children (63 girls, 40 boys; age range 1-14 years; mean age 6.57 years) referred for various complaints who had IHC. Renal echography was routinely performed. At diagnosis, 52 children had RCM, 35 showed normal echography, 14 had calculi and two presented nephrocalcinosis. A long-term follow-up study was carried out to compare the clinical manifestations, analytic data and renal echographic findings of patients with RCM and those with normal echography.<br><br>RESULTS: The clinical manifestations and the results of biochemical studies did not differ significantly between the two groups. Renal sonographic findings during the follow-up period revealed that, of patients with initial RCM, 35 showed normalized sonographic findings, two developed calculi and 36 developed recurrent RCM. Of the children with normal initial echography, 17 developed RCM and three developed calculi. The risk of developing lithiasis was less in children with RCM than in those with normal initial renal echography (0.04 vs 0.09), the relative risk being 0.45 (95% CI 0.08-2.55). The clinical and analytic differences between the group of 14 children with initial lithiasis and the other two groups previously described were also analyzed and no significant differences were found. An ongoing echographic study of these patients showed that the echograph was normalized in 10 children at some point or other, while seven developed RCM (four unilateral, three bilateral). In 13 cases the lithiasis reappeared, and the relative risk of recurrent lithiasis compared with those who initially showed no lithiasis was 16.16 (CI 95% 6.81-38.31).<br><br>CONCLUSION: Our results indicate that up to 85% of children with IHC presented RCM in follow-up sonographies. This echographic finding, which may appear and disappear at different points during follow-up, does not seem to indicate an increased risk of lithiasis.}, }
@article {pmid15763005, year = {2005}, author = {Amaro, CR and Goldberg, J and Amaro, JL and Padovani, CR}, title = {Metabolic assessment in patients with urinary lithiasis.}, journal = {International braz j urol : official journal of the Brazilian Society of Urology}, volume = {31}, number = {1}, pages = {29-33}, doi = {10.1590/s1677-55382005000100006}, pmid = {15763005}, issn = {1677-5538}, mesh = {Acidosis, Renal Tubular/metabolism ; Adult ; Brazil/epidemiology ; Calcium/metabolism ; Creatinine/metabolism ; Female ; Humans ; Hydrogen-Ion Concentration ; Hypercalcemia/metabolism ; Hyperoxaluria/metabolism ; Hyperparathyroidism/metabolism ; Magnesium/metabolism ; Male ; Middle Aged ; Oxides/metabolism ; Phosphorus/metabolism ; Potassium/metabolism ; Prevalence ; Prospective Studies ; Sodium/metabolism ; Uric Acid/metabolism ; Urinary Calculi/epidemiology/*metabolism ; }, abstract = {INTRODUCTION: Metabolic investigation in patients with urinary lithiasis is very important for preventing recurrence of disease. The objective of this work was to diagnose and to determine the prevalence of metabolic disorders, to assess the quality of the water consumed and volume of diuresis as potential risk factors for this pathology.<br><br>PATIENTS AND METHODS: We studied 182 patients older than 12 years. We included patients with history and/or imaging tests confirming at least 2 stones, with creatinine clearance > or = 60 mL/min and negative urine culture. The protocol consisted in the collection of 2, 24-hour urine samples, for dosing Ca, P, uric acid, Na, K, Mg, Ox and Ci, glycemia and serum levels of Ca, P, Uric acid, Na, K, Cl, Mg, U and Cr, urinary pH and urinary acidification test.<br><br>RESULTS: 158 patients fulfilled the inclusion criteria. Among these, 151 (95.5%) presented metabolic changes, with 94 (62.2%) presenting isolated metabolic change and 57 (37.8%) had mixed changes. The main disorders detected were hypercalciuria (74%), hypocitraturia (37.3%), hyperoxaluria (24.1%), hypomagnesuria (21%), hyperuricosuria (20.2%), primary hyperparathyroidism (1.8%), secondary hyperparathyroidism (0.6%) and renal tubular acidosis (0.6).<br><br>CONCLUSION: Metabolic change was diagnosed in 95.5% of patients. These results warrant the metabolic study and follow-up in patients with recurrent lithiasis in order to decrease the recurrence rate through specific treatments, modification in alimentary and behavioral habits.}, }
@article {pmid15752294, year = {2005}, author = {Fabre, B and Bayle, P and Bazex, J and Durand, D and Lamant, L and Chassaing, N}, title = {Pseudoxanthoma elasticum and nephrolithiasis.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {19}, number = {2}, pages = {212-215}, doi = {10.1111/j.1468-3083.2005.01007.x}, pmid = {15752294}, issn = {0926-9959}, mesh = {Adult ; Calcium/metabolism ; Humans ; Kidney Calculi/*complications ; Male ; Mutation ; Phosphates/metabolism ; Pseudoxanthoma Elasticum/*complications/genetics ; Recurrence ; Skin/pathology ; }, abstract = {We report the case of a 42-year-old man with pseudoxanthoma elasticum (PXE) and recurrent bilateral nephrolithiasis. Diagnosis of PXE was made by yellow papules on the neck and ophthalmologic angioid streaks. This diagnosis was confirmed by a skin biopsy (Von Kossa stain) and by genotyping analysis of ABCC6 (homozygous mutation R1138Q). Nephrolithiasis was recurrent and biological investigations showed hypophosphoraemia, hyperphosphaturia, hypercalciuria, normocalcaemia, normal serum parathyroid hormone value, high 1,25-dihydroxy vitamin D value and a renal calcium oxalate stone. ABCC6 encodes for MRP6, a multidrug resistant protein strongly expressed in the liver and kidney. The substrates of the MRP6 remain unknown. As PXE is characterized by calcification of elastic fibres and this patient presents important phosphocalcic anomalies, we discuss the possible implications of MRP6 in the phosphocalcic metabolism.}, }
@article {pmid15748409, year = {2002}, author = {Pearle, MS}, title = {Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism.}, journal = {International braz j urol : official journal of the Brazilian Society of Urology}, volume = {28}, number = {6}, pages = {571-572}, pmid = {15748409}, issn = {1677-5538}, }
@article {pmid15722151, year = {2005}, author = {McNamara, CJ and Perry, TD and Bearce, K and Hernandez-Duque, G and Mitchell, R}, title = {Measurement of limestone biodeterioration using the Ca2+ binding fluorochrome Rhod-5N.}, journal = {Journal of microbiological methods}, volume = {61}, number = {2}, pages = {245-250}, doi = {10.1016/j.mimet.2004.12.004}, pmid = {15722151}, issn = {0167-7012}, mesh = {Biodegradation, Environmental ; Calcium/*metabolism ; Calcium Carbonate/*chemistry ; Fluorescent Dyes/*chemistry ; Gram-Positive Endospore-Forming Rods/*metabolism ; Spectrometry, Fluorescence ; }, abstract = {Limestone and marble have been used extensively in the construction of modern and historic buildings. Microbial colonization and growth on these stone structures is common. Microbial deterioration of stone has been assessed by measuring Ca2+ released from the stone, using ion selective electrodes and titration with EDTA. In this study, the calcium binding fluorochrome Rhod-5N was used to measure Ca2+ released from limestone by endolithic bacteria as an indicator of biodeterioration. In a 17 d flask experiment, Ca2+ released by endolithic bacteria was twice that of uninoculated controls. Rhod-5N is a rapid and accurate method for measuring microbial biodeterioration of stone.}, }
@article {pmid15692680, year = {2005}, author = {Rebelo, MA and Tostes, V and Araújo, NC and Martini, SV and Botelho, BF and Guggino, WB and Morales, MM}, title = {Screening for CLCN5 mutation in renal calcium stone formers patients.}, journal = {Anais da Academia Brasileira de Ciencias}, volume = {77}, number = {1}, pages = {95-101}, doi = {10.1590/s0001-37652005000100007}, pmid = {15692680}, issn = {0001-3765}, support = {DK 32753/DK/NIDDK NIH HHS/United States ; HL 47122/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Base Sequence ; Chloride Channels/*genetics ; Creatinine/urine ; Female ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; Kidney Calculi/*genetics/urine ; Male ; Molecular Sequence Data ; Molecular Weight ; *Mutation ; Nephrocalcinosis/*genetics/urine ; Polymerase Chain Reaction ; Renal Insufficiency/*genetics/urine ; Severity of Illness Index ; beta 2-Microglobulin/urine ; }, abstract = {UNLABELLED: Thirty-five patients (23 males and 12 females), age 35 +/- 13 years old, presenting either idiopathic calcium nephrolithiasis, nephrocalcinosis or mild renal failure with idiopathic calcium nephrolithiasis were selected for the analysis of low molecular weight proteinuria and the possible mutations occurrence in the chloride channel gene CLCN5. The urinary ratio of beta2-microglobulin and creatinine (beta2M/Cr) was very high in a transplanted woman with nephrocalcinosis (> 3.23 mg/mmol) and slightly high in five patients (> 0.052 or < 1.0 mg/mmol) with multiple urological manipulations. Other studied patients showed beta2M/Cr ratio at normal range (0.003-0.052 mg/mmol) without gender difference (p > 0.05). Mutation analysis of CLCN5 gene was performed in 26 patients of 35 selected (11 with idiopathic hypercalciuria; 6 men with normal calciuria; 3 with mild renal insufficiency and 6 with nephrocalcinosis) and was normal in all subjects even in those with abnormal molecular weight proteinuria.<br><br>CONCLUSION: CLCN5 gene mutation is not a common cause of kidney stone disease or nephrocalcinosis in a group of Brazilian patients studied.}, }
@article {pmid15689405, year = {2005}, author = {Moe, OW and Bonny, O}, title = {Genetic hypercalciuria.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {16}, number = {3}, pages = {729-745}, doi = {10.1681/ASN.2004100888}, pmid = {15689405}, issn = {1046-6673}, support = {R01 DK 48482/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/*urine ; Calcium Metabolism Disorders/*genetics/*physiopathology ; Humans ; Kidney Calculi/*genetics/*physiopathology ; }, abstract = {Hypercalciuria is an important, identifiable, and reversible risk factor in stone formation. The foremost and most fundamental step in dissecting the genetics of hypercalciuria is understanding its pathophysiology. Hypercalciuria is a complex trait. This article outlines the various factors that compromise the attempt to dissect the genetics of hypercalciuria, summarizes the clinical and experimental monogenic causes of hypercalciuria, and outlines the initial results from attempts in studying polygenic hypercalciuria. Finally, the problem is set in perspective of the current database, technologic advances and limitations are highlighted, and prospects of further advances in the field are speculated upon.}, }
@article {pmid15688852, year = {2004}, author = {Kazantzis, G}, title = {Cadmium, osteoporosis and calcium metabolism.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {17}, number = {5}, pages = {493-498}, doi = {10.1023/b:biom.0000045727.76054.f3}, pmid = {15688852}, issn = {0966-0844}, mesh = {Belgium ; Bone and Bones/drug effects ; Cadmium/*toxicity ; Cadmium Poisoning/*complications ; Calcium/*metabolism ; China ; Environmental Exposure ; Female ; Humans ; Japan ; Kidney Calculi/etiology ; Male ; *Occupational Diseases ; Osteomalacia/etiology ; Osteoporosis/*etiology ; Sweden ; }, abstract = {Occupational exposure to cadmium has for long been associated with renal tubular cell dysfunction, osteomalacia with osteoporosis, hypercalciuria and renal stone formation. High environmental exposure in Japan resulting from a stable diet of cadmium contaminated rice caused itai-itai disease, fractures occurring mainly in elderly multiparous women, with a form of osteomalacia, osteoporosis and renal dysfunction. More recently a population based study in Europe, in the vicinity of zinc smelters has shown that low to moderate exposure to cadmium, with a mean urinary excretion of cadmium of the order of 1 microg/g creatinine has been associated with a decrease in bone density, an increased risk of bone fractures in women and of height loss in men. In a population-based study of residents near a cadmium smelter in China, forearm bone density was shown to decrease linearly with age and urinary cadmium in both sexes, suggesting a dose effect relationship between cadmium dose and bone mineral density. A marked increase in the prevalence of fractures was shown in the cadmium-polluted area in both sexes. Concentrations of cadmium in blood and urine were taken as exposure biomarkers, and beta2-microglobulin, retinol binding protein and albumin as biomarkers of effect. A marked dose response relationship between these indicators of exposure and effect was shown. Hypercalciuria, which may progress to osteoporosis, has been taken as a sensitive renal-tubular biomarker of a low level of cadmium exposure. Cadmium may also act directly on bone. Animal studies have shown cadmium to stimulate the formation and activity of osteoclasts, breaking down the collagen matrix in bone. Osteoporosis is the main cause of fracures in post-menopausal women, a common occurrence worldwide, giving rise to disability and a high cost to health services. The identification of cadmium, an environmental pollutant, as one causal factor is highly significant in helping to control the incidence of this complex condition.}, }
@article {pmid15655568, year = {2005}, author = {Vaidyanathan, S and Watson, ID and Jonsson, O and Buczynski, AZ and Grases, F and Heilberg, IP and Yasui, T and Wyndaele, JJ and Tozawa, K and Kohri, K and Schurch, B and Hughes, PL and Singh, G and Soni, BM and Sett, P and Fraser, WD}, title = {Recurrent vesical calculi, hypercalciuria, and biochemical evidence of increased bone resorption in an adult male with paraplegia due to spinal cord injury: is there a role for intermittent oral disodium etidronate therapy for prevention of calcium phosphate bladder stones?.}, journal = {Spinal cord}, volume = {43}, number = {5}, pages = {269-277}, doi = {10.1038/sj.sc.3101713}, pmid = {15655568}, issn = {1362-4393}, mesh = {Adult ; Bone Resorption/etiology ; Calcium/*metabolism ; Etidronic Acid/*therapeutic use ; Follow-Up Studies ; Humans ; International Cooperation ; Male ; Paraplegia/*etiology/metabolism/pathology ; Spinal Cord Injuries/*complications/metabolism/pathology ; Tomography, X-Ray Computed/methods ; Urinary Bladder Calculi/etiology ; Urinary Calculi/etiology/pathology/*prevention &amp; control ; }, abstract = {STUDY DESIGN: Clinical case report with comments by colleagues from Sweden, Poland, Spain, Brazil, Japan, Belgium and Switzerland.<br><br>OBJECTIVES: To discuss the role of disodium etidronate therapy for prevention of calcium phosphate vesical calculi in persons with spinal cord injury, who have hypercalciuria and biochemical evidence of increased bone resorption.<br><br>SETTING: Regional Spinal Injuries Centre, Southport, UK.<br><br>METHODS: A 21-year-old male sustained paraplegia (T-10; ASIA scale: A) in a road traffic accident in June 2001. He had an indwelling urethral catheter until the end of August 2001, when he started self-catheterisation. He developed bladder stones and electrohydraulic lithotripsy (EHL) was performed in May 2002. All stone fragments were removed. Recurrence of vesical calculi was noted in October 2002. These stones were fragmented by lithoclast lithotripsy in two sessions, in December 2002 and February 2003; all stone fragments were removed at the end of the second session. This patient reverted to indwelling catheter drainage when vesical calculi recurred. In September 2003, X-ray of the abdomen showed recurrence of vesical calculi. By February 2004, the stones had increased in size and number. EHL of vesical calculi was again performed in April 2004. Complete clearance was achieved.<br><br>RESULTS: A 24-h urinalysis detected hypercalciuria--18.7 mmol/day (reference range: 2.5-7.5). Biochemical analysis of vesical calculus revealed calcium phosphate (85%) and magnesium ammonium phosphate (15%). Plasma C-terminal telopeptide (CTX) was increased - 1.06 ng/ml (reference range: 0.1-0.5 ng/ml). Free deoxypyridinoline/creatinine ratio (fDPD/Cr) in urine was also increased - 20.2 (reference range: 2.3-5.4). In April 2004, this patient was prescribed disodium etidronate 400 mg day. Nearly 3 months after commencing therapy with etidronate, plasma CTX decreased to 0.87 ng/ml. fDPD/Cr in urine also decreased to 12.4. After 4 months of etidronate therapy, 24-h urinary calcium excretion had decreased to 6.1 mmol/day.<br><br>CONCLUSION: Etidronate (400 mg daily) is a very effective inhibitor of calcium phosphate crystallisation. Etidronate decreased urinary excretion of calcium, an important factor in prevention of calcium phosphate bladder stones. Etidronate therapy is not a substitute for other well-established methods for prevention of vesical calculi in spinal cord injury patients, for example, large fluid intake, avoiding long-term catheter drainage. Intermittent therapy with etidronate may be considered in selected patients, in whom hypercalciuria persists after instituting nonpharmacological therapy for an adequate period, for example, early mobilisation, weight-bearing exercises, and functional electrical stimulation. However, possible side effects of etidronate, and the fact that etidronate is not licensed in United Kingdom for prevention of urolithiasis, should be borne in mind.}, }
@article {pmid15637424, year = {2005}, author = {Devuyst, O and Jouret, F and Auzanneau, C and Courtoy, PJ}, title = {Chloride channels and endocytosis: new insights from Dent's disease and ClC-5 knockout mice.}, journal = {Nephron. Physiology}, volume = {99}, number = {3}, pages = {p69-73}, doi = {10.1159/000083210}, pmid = {15637424}, issn = {1660-2137}, mesh = {Animals ; Chloride Channels/*deficiency/genetics/metabolism ; *Endocytosis ; *Ion Channel Gating ; Kidney Calculi/genetics/*metabolism ; Kidney Tubules, Proximal/*metabolism ; Low Density Lipoprotein Receptor-Related Protein-2/*metabolism ; Mice ; Mice, Knockout ; Tubulin/*metabolism ; }, abstract = {Dent's disease is a hereditary renal tubular disorder characterized by low-molecular weight (LMW) proteinuria, hypercalciuria and nephrolithiasis. The disease is due to mutations of ClC-5, a member of the family of voltage-gated CLC chloride channels. ClC-5 is expressed in part in cells lining the proximal tubule (PT) of the kidney, where it colocalizes with albumin-containing endocytic vesicles belonging to the receptor-mediated endocytic pathway that ensures efficient reabsorption of ultrafiltrated LMW proteins. Since progression along the endocytic apparatus requires endosomal acidification, it has been suggested that dysfunction of ClC-5 in endosomes may lead to inefficient reabsorption of LMW proteins and dysfunction of PT cells. Analysis of a ClC-5 knockout (KO) mouse model, displaying all the characteristic renal tubular defects of Dent's disease, showed evidence of a severe LMW proteinuria. Cytochemical studies with the endocytic tracer, peroxidase, showed poor transfer into early endocytic vesicles, suggesting that impairment of receptor-mediated endocytosis in PT cells is the basis for the defective uptake of LMW proteins in patients with Dent's disease. Endocytosis and processing of LMW proteins involve the multiligand tandem receptors, megalin and cubilin, that are abundantly expressed at the brush border of PT cells. Characterization of the endocytic defect in ClC-5 KO mice revealed that ligands of both megalin and cubilin were affected. The total kidney content of megalin and especially cubilin at the protein level was decreased but, more importantly, using analytical subcellular fractionation and quantitative immunogold labelling we demonstrated a selective disappearance of megalin and cubilin at the brush border of PT cells. These observations allowed us to conclude that defective protein endocytosis linked to ClC-5 inactivation is due at least in part to a major and selective loss of megalin and cubilin at the brush border, reflecting a trafficking defect in renal PT cells. These results improve our understanding of Dent's disease, taken as a paradigm for renal Fanconi syndrome and nephrolithiasis, and demonstrate multiple roles for ClC-5 in the kidney. These studies also provided insights into important functions such as apical endocytosis, handling of proteins by renal tubular cells, calcium metabolism, and urinary acidification.}, }
@article {pmid15636725, year = {2004}, author = {Serra, A and Domingos, F and Salgueiro, C and Prata, MM}, title = {[Metabolic evaluation of recurrent idiopathic calcium stone disease in Portugal].}, journal = {Acta medica portuguesa}, volume = {17}, number = {1}, pages = {27-34}, pmid = {15636725}, issn = {1646-0758}, mesh = {Adult ; Aged ; Calcium/analysis/*metabolism ; Female ; Humans ; Kidney Calculi/*metabolism ; Male ; Middle Aged ; Portugal ; Recurrence ; }, abstract = {BACKGROUND: Idiopathic calcium stone disease is the most frequent type of nephrolithiasis in industrialised countries. Several metabolic, environmental and genetic factors have described and may be involved in its pathogenesis. This study was designed to evaluate the factors that contribute to idiopathic calcium stone disease in Portugal.<br><br>METHODS: To characterise the Portuguese population with idiopathic recurrent calcium stone disease, a population of 87 consecutive idiopathic recurrent calcium stone formers (IRCSF) was evaluated over a 5-year period. The results were compared with a control group of 45 healthy subjects (HS) from the same population, with similar age and gender distribution.<br><br>RESULTS: No difference was observed in the distribution of affected individual according to gender (47 females and 40 males). A familial history of nephrolithiasis was present in 35.6%. Significantly higher urinary calcium and lower urinary citrate were observed in IRCSF group when compared with HS group. Individual analysis revealed urinary abnormalities in 78 of 87 IRCSF (89.7%). Hyperoxaluria was the most frequent abnormality, observed in 40.2% of the patients, hyperuricosuria in 33.3%, hypercalciuria in 24.1%, hypocitraturia in 23.0%, low urine volume in 19.5% and hypomagnesiuria in 8%. No difference was observed in the distribution of urinary risk factors according to gender or presence of familial antecedents of nephrolithiasis. A positive correlation was observed between urinary sodium and calcium in hypercalciuric patients.<br><br>CONCLUSIONS: Among the studied population, idiopathic calcium nephrolithiasis affected both genders equally. Metabolic evaluation permits the identification of urine abnormalities in most of these patients. Hyperoxaluria, hypercalciuria, hypocitraturia and hyperuricosuria appeared as important pathogenic factors in IRCSF. Urine volume was not different between groups. Dietary factors may be involved in the observed urine abnormalities and need to be further evaluated.}, }
@article {pmid15632477, year = {2005}, author = {Fujita, T}, title = {[Active absorbable algal calcium (AAACa) changes calcium paradigm].}, journal = {Clinical calcium}, volume = {15}, number = {1}, pages = {87-93}, pmid = {15632477}, issn = {0917-5857}, mesh = {Adipose Tissue/drug effects ; Animals ; Bone Density/drug effects ; *Calcium/metabolism/pharmacology/*therapeutic use ; *Calcium Carbonate ; Depression, Chemical ; Heating ; Humans ; Hypocalcemia/*drug therapy/metabolism ; Intestinal Absorption ; Osteoporosis/*drug therapy/metabolism ; *Oxides ; Parathyroid Hormone/metabolism ; *Seaweed ; Spinal Fractures/prevention &amp; control ; Urinary Calculi/prevention &amp; control ; }, abstract = {Active Absorbable Algal Calcium (AAA Ca) is made by submaximally (800 degrees) heating cleaned oyster shell under reduced pressure and mixing it with similarly heated seaweed (Cystophyllum fusiforme). AAA Ca, the best absorbed from the intestine than other available calcium compounds, consequently most efficiently suppresses parathyroid hormone secretion, increases bone mineral density and decreases vertebral fracture. Aging is associated with calcium deficiency, mostly because of the decreased biosynthesis of 1,25 (OH)2 vitamin D in the kidney. Parathyroid hormone consequently increases, contributing to various diseases associated with aging such as osteoporosis or decrease of calcium in the bone, as well as hypertension, arteriosclerosis, Alzheimer's disease and osteoarthritis due to paradoxical increase of calcium in vascular walls, brain, cartilage and intracellular compartment of many kinds of cells. Mild calcium deficiency is hard to detect despite these serious consequences because of the remarkable constancy of blood calcium concentration maintained by elaborate homeostatic control. Only by successfully counteracting calcium deficiency by AAA Ca with outstanding absorbability, the phenomenon of calcium paradox becomes a recognizable reality within our reach.}, }
@article {pmid15615421, year = {2003}, author = {Cao, ZG and Liu, JH and Radman, AM and Wu, JZ and Ying, CP and Zhou, SW}, title = {[An experimental study of effect of different extracts of Alisma orientalis on urinary calcium oxalate stones formation in rats].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {28}, number = {11}, pages = {1072-1075}, pmid = {15615421}, issn = {1001-5302}, mesh = {*Alisma/chemistry ; Ammonium Chloride ; Animals ; Blood Urea Nitrogen ; Calcium/metabolism ; Calcium Oxalate/*urine ; Creatinine/blood ; Drugs, Chinese Herbal/isolation &amp; purification/*pharmacology ; Ethylene Glycol ; Kidney/*metabolism ; Kidney Calculi/chemically induced/*metabolism/prevention &amp; control ; Magnesium/metabolism/urine ; Male ; Rats ; Rats, Wistar ; }, abstract = {OBJECTIVE: To study the effect of different extracts of Alisma orientalis on urinary calcium oxalate stone formation in rats and to identify the effective constituents.<br><br>METHOD: Different extracts were administered through a stomach tube to rats of different groups with renal calcium oxalate stones induced by ethylene glycol (EG) and ammonium chloride (AC).<br><br>RESULT: In the rats administered with ethyl acetate elution of ethyl acetate extract, blood Cr, BUN, renal tissue calcium content, urinary calcium excretion and crystals deposition in renal tissue were significantly lower than those of the stone formation group.<br><br>CONCLUSION: The ethyl acetate elution of ethyl acetate fraction extract of Alisma orientalis can significantly inhibit urinary calcium oxalate stone formation in rats and be the most effective constituent of Alisma orientalis.}, }
@article {pmid15615095, year = {2004}, author = {Devuyst, O}, title = {Chloride channels and endocytosis: new insights from Dent's disease and CLC-5 knockout mice.}, journal = {Bulletin et memoires de l'Academie royale de medecine de Belgique}, volume = {159}, number = {Pt 2}, pages = {212-217}, pmid = {15615095}, issn = {0377-8231}, mesh = {Animals ; Calcium/analysis ; Chloride Channels/*genetics ; Disease Models, Animal ; *Endocytosis ; Kidney Calculi/chemistry/*genetics/*physiopathology ; Mice ; Mice, Knockout ; }, abstract = {Dent's disease is an hereditary renal tubular disorder characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria and nephrolithiasis. The disease is due to mutations of CLC-5, a member of the family of voltage-gated CLC chloride channels. CLC-5 is distributed in cells lining the proximal tubule (PT) of the kidney, where it co-localizes with albumin-containing endocytic vesicles that form part of the receptor-mediated endocytic pathway that mediates the reabsorption of low-molecular-weight (LMW) proteins filtered at the glomerular level. Since progression along the endocytic apparatus requires endosomal acidification, it has been suggested that dysfunction of CLC-5 in endosomes may lead to inefficient reabsorption of LMW proteins and dysfunction of PT cells. Investigations conducted in a CLC-5 knockout (KO) mouse model harbouring all the characteristic renal tubular defects of Dent's disease showed a severe impairment of endocytosis by PT cells, such that the endocytic tracer peroxidase was poorly transferred into early endocytic vesicles. These data demonstrated that an impairment of receptor-mediated endocytosis in PT cells is the basis for the defective uptake of LMW proteins in patients with Dent's disease. The endocytosis and processing of LMW proteins involves the multiligand tandem receptors, megalin and cubilin, that are abundantly expressed at the brush border of PT cells. The characterization of the endocytic defect in CLC-5 KO mice revealed that ligands of both megalin and cubilin were affected, whereas a decrease in total kidney content of megalin and cubilin at the protein level was detected. Using analytical subcellular fractionation and quantitative immunogold labelling, we demonstrated a selective disappearance of megalin and cubilin at the brush border of PT cells. These observations allowed us to conclude that defective protein endocytosis linked to CLC-5 inactivation is due to a major and selective loss of megalin and cubilin at the brush border, reflecting a trafficking defect in renal PT cells. These results improve our understanding of Dent's disease, taken as a paradigm for renal Fanconi syndrome and nephrolithiasis, and demonstrate multiple roles for CLC-5 in the kidney. These studies also provided insights in important functions such as apical endocytosis, handling of proteins by renal tubular cells, calcium metabolism, and urinary acidification.}, }
@article {pmid15613438, year = {2005}, author = {Bevilacqua, M and Dominguez, LJ and Righini, V and Valdes, V and Toscano, R and Sangaletti, O and Vago, T and Baldi, G and Barrella, M and Bianchi-Porro, G}, title = {Increased gastrin and calcitonin secretion after oral calcium or peptones administration in patients with hypercalciuria: a clue to an alteration in calcium-sensing receptor activity.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {90}, number = {3}, pages = {1489-1494}, doi = {10.1210/jc.2004-0045}, pmid = {15613438}, issn = {0021-972X}, mesh = {Administration, Oral ; Aged ; Calcitonin/*metabolism ; Calcium Gluconate/administration &amp; dosage/urine ; Calcium Metabolism Disorders/diagnosis/*urine ; Female ; Gastrin-Secreting Cells/drug effects/metabolism ; Gastrins/*metabolism ; Humans ; Kidney Calculi/diagnosis/urine ; Middle Aged ; Parathyroid Hormone/metabolism ; Peptones/administration &amp; dosage ; Receptors, Calcium-Sensing/*metabolism ; Thyroid Gland/drug effects/metabolism ; }, abstract = {The calcium-sensing receptor (CaSR) has been detected in human antral gastrin-secreting cells, where, upon calcium and/or amino acid allosteric activation, it stimulates gastrin secretion. Patients with absorptive hypercalciuria (AH) display an enhanced gastric acid output; therefore, we evaluated the secretion of gastrin in subjects with AH (30 subjects vs. 30 healthy female controls, all postmenopausal) after oral calcium administration (1 g calcium gluconate) and, on a separate occasion, after peptone loading test (protein hydrolyzed, 10 g). Gastrin and monomeric calcitonin responses were higher in AH after both oral calcium administration (P < 0.01) and peptone loading (P < 0.01). Because the activation of CaSR by oral calcium and peptones directly induces gastrin release, the higher gastrin responses to these stimuli suggest an increased sensitivity of gastrin-secreting cells CaSR in patients with AH. A similar alteration in thyroid C cells might explain the enhanced calcitonin responses to both calcium and peptones. If the same alterations should in addition be present in the distal tubule (where CaSR is expressed as well), then a possible explanation for amino acid-induced hypercalciuria in AH would have been identified.}, }
@article {pmid15590899, year = {2005}, author = {Karl, MO and Fleischhauer, JC and Stamer, WD and Peterson-Yantorno, K and Mitchell, CH and Stone, RA and Civan, MM}, title = {Differential P1-purinergic modulation of human Schlemm's canal inner-wall cells.}, journal = {American journal of physiology. Cell physiology}, volume = {288}, number = {4}, pages = {C784-94}, doi = {10.1152/ajpcell.00333.2004}, pmid = {15590899}, issn = {0363-6143}, support = {EY-12797/EY/NEI NIH HHS/United States ; R01 EY015537/EY/NEI NIH HHS/United States ; EY-01583/EY/NEI NIH HHS/United States ; EY-013624/EY/NEI NIH HHS/United States ; EY-13434/EY/NEI NIH HHS/United States ; R01 EY013434/EY/NEI NIH HHS/United States ; }, mesh = {Anterior Eye Segment/*cytology/*metabolism ; Aqueous Humor/physiology ; Calcium/metabolism ; Cell Culture Techniques/*methods ; Cells, Cultured ; Humans ; Intracellular Fluid/drug effects/metabolism ; Intraocular Pressure/drug effects/physiology ; Membrane Potentials/drug effects ; Patch-Clamp Techniques ; *Purinergic P1 Receptor Agonists ; *Purinergic P1 Receptor Antagonists ; Receptors, Purinergic P1/drug effects/*physiology ; }, abstract = {Intraocular pressure is directly dependent on aqueous humor flow into, and resistance to flow out of, the eye. Adenosine has complex effects on intraocular pressure. Stimulation of A1 and A2A adenosine receptors changes intraocular pressure oppositely, likely through opposing actions on the outflow of aqueous humor. While the cellular sites regulating outflow resistance are unknown, the cells lining the inner wall of Schlemm's canal (SC) are a likely regulatory site. We applied selective adenosine receptor agonists to SC cells in vitro to compare the responses to A1 and A2A stimulation. Parallel studies were conducted with human inner-wall SC cells isolated by a novel enzyme-assisted technique and with cannula-derived mixed inner- and outer-wall SC cells. A1 agonists increased whole cell currents of both inner-wall and cannula-derived SC cells. An A2A agonist reduced currents most consistently in specifically inner-wall SC cells. Those currents were also increased by A2B, but not consistently affected by A3, stimulation. A1, A2A, and A3 agonists all increased SC-cell intracellular Ca2+. The electrophysiological results are consistent with the possibility that inner-wall SC cells may mediate the previously reported modulatory effects of adenosine on outflow resistance. The results are also consistent with the presence of functional A2B, as well as A1, A2A, and A3 adenosine receptors in SC cells.}, }
@article {pmid15588827, year = {2005}, author = {King, WA and Stone, DB and Timmins, PA and Narayanan, T and von Brasch, AA and Mendelson, RA and Curmi, PM}, title = {Solution structure of the chicken skeletal muscle troponin complex via small-angle neutron and X-ray scattering.}, journal = {Journal of molecular biology}, volume = {345}, number = {4}, pages = {797-815}, doi = {10.1016/j.jmb.2004.10.090}, pmid = {15588827}, issn = {0022-2836}, support = {AR45659/AR/NIAMS NIH HHS/United States ; RR-01081/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism/pharmacology ; *Chickens ; Models, Molecular ; Multiprotein Complexes/chemistry/metabolism ; Muscle, Skeletal/*chemistry ; Myocardium/chemistry ; *Neutron Diffraction ; Protein Binding ; Protein Structure, Quaternary/drug effects ; Protein Subunits/chemistry/metabolism ; Solutions/chemistry ; Troponin/*chemistry/*metabolism ; X-Ray Diffraction ; }, abstract = {Troponin is a Ca2+-sensitive switch that regulates the contraction of vertebrate striated muscle by participating in a series of conformational events within the actin-based thin filament. Troponin is a heterotrimeric complex consisting of a Ca2+-binding subunit (TnC), an inhibitory subunit (TnI), and a tropomyosin-binding subunit (TnT). Ternary troponin complexes have been produced by assembling recombinant chicken skeletal muscle TnC, TnI and the C-terminal portion of TnT known as TnT2. A full set of small-angle neutron scattering data has been collected from TnC-TnI-TnT2 ternary complexes, in which all possible combinations of the subunits have been deuterated, in both the +Ca2+ and -Ca2+ states. Small-angle X-ray scattering data were also collected from the same troponin TnC-TnI-TnT2 complex. Guinier analysis shows that the complex is monomeric in solution and that there is a large change in the radius of gyration of TnI when it goes from the +Ca2+ to the -Ca2+ state. Starting with a model based on the human cardiac troponin crystal structure, a rigid-body Monte Carlo optimization procedure was used to yield models of chicken skeletal muscle troponin, in solution, in the presence and in the absence of regulatory calcium. The optimization was carried out simultaneously against all of the scattering data sets. The optimized models show significant differences when compared to the cardiac troponin crystal structure in the +Ca2+ state and provide a structural model for the switch between +Ca2+ and -Ca2+ states. A key feature is that TnC adopts a dumbbell conformation in both the +Ca2+ and -Ca2+ states. More importantly, the data for the -Ca2+ state suggest a long extension of the troponin IT arm, consisting mainly of TnI. Thus, the troponin complex undergoes a large structural change triggered by Ca2+ binding.}, }
@article {pmid15569313, year = {2004}, author = {Procino, G and Carmosino, M and Tamma, G and Gouraud, S and Laera, A and Riccardi, D and Svelto, M and Valenti, G}, title = {Extracellular calcium antagonizes forskolin-induced aquaporin 2 trafficking in collecting duct cells.}, journal = {Kidney international}, volume = {66}, number = {6}, pages = {2245-2255}, doi = {10.1111/j.1523-1755.2004.66036.x}, pmid = {15569313}, issn = {0085-2538}, mesh = {Actins/metabolism ; Animals ; Aquaporin 2 ; Aquaporins/*metabolism ; Calcium/*metabolism/pharmacology ; Cells, Cultured ; Colforsin/*pharmacology ; Cyclic AMP/metabolism ; Extracellular Space/metabolism ; Gadolinium/pharmacology ; Kidney Tubules, Collecting/cytology/drug effects/*metabolism ; Protein Kinase C/metabolism ; Protein Transport/drug effects/physiology ; Rabbits ; Receptors, Calcium-Sensing/metabolism ; Signal Transduction/drug effects/physiology ; Stress Fibers/metabolism ; }, abstract = {BACKGROUND: Urinary concentrating defects and polyuria are the most important renal manifestations of hypercalcemia and the resulting hypercalciuria. In this study, we tested the hypothesis that hypercalciuria-associated polyuria in kidney collecting duct occurs through an impairment of the vasopressin-dependent aquaporin 2 (AQP2) water channel targeting to the apical membrane possibly involving calcium-sensing receptor (CaR) signaling.<br><br>METHODS: AQP2-transfected collecting duct CD8 cells were used as experimental model. Quantitation of cell surface AQP2 immunoreactivity was performed using an antibody recognizing the extracellular AQP2 C loop. Intracellular cyclic adenosine monophosphate (cAMP) accumulation was measured in CD8 cells using a cAMP enzyme immunoassay kit. To study the translocation of protein kinase C (PKC), membranes or cytosol fractions from CD8 cells were subjected to Western blotting using anti-PKC isozymes antibodies. The amount of F-actin was determined by spectrofluorometric techniques. Intracellular calcium measurements were performed by spectrofluorometric analysis with Fura-2/AM.<br><br>RESULTS: We demonstrated that extracellular calcium (Ca2+ o) (5 mmol/L) strongly inhibited forskolin-stimulated increase in AQP2 expression in the apical plasma membrane. At least three intracellular pathways activated by extracellular calcium were found to contribute to this effect. Firstly, the increase in cAMP levels in response to forskolin stimulation was drastically reduced in cells pretreated with Ca2+ o compared to untreated cells. Second, Ca2+ o activated PKC, known to counteract vasopressin response. Third, quantification of F-actin demonstrated that Ca2+ o caused a nearly twofold increase in F-actin content compared with basal conditions. All these effects were mimicked by a nonmembrane permeable agonist of the extracellular CaR, Gd3+.<br><br>CONCLUSION: Together, these data demonstrate that extracellular calcium, possibly acting through the endogenous CaR, antagonizes forskolin-induced AQP2 translocation to the apical plasma membrane in CD8 cells. In hypercalciuria, this mechanism might blunt water reabsorption and prevent further calcium concentration, thus protecting against a potential risk of urinary calcium-containing stone formation.}, }
@article {pmid15558518, year = {2004}, author = {Gambaro, G and Vezzoli, G and Casari, G and Rampoldi, L and D'Angelo, A and Borghi, L}, title = {Genetics of hypercalciuria and calcium nephrolithiasis: from the rare monogenic to the common polygenic forms.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {44}, number = {6}, pages = {963-986}, doi = {10.1053/j.ajkd.2004.06.030}, pmid = {15558518}, issn = {1523-6838}, mesh = {Animals ; Calcium/*urine ; Calcium Metabolism Disorders/*genetics ; *Genetics, Medical ; Humans ; Nephrocalcinosis/*genetics ; Phenotype ; }, abstract = {Idiopathic calcium nephrolithiasis is a multifactorial disease with a pathogenesis that involves a complex interaction of environmental and individual factors. This review discusses what is known about monogenic renal calcium stone-related disorders, provides an update on genetic research in calcium nephrolithiasis and such intermediate phenotypes as idiopathic hypercalciuria, discusses the problems that these conditions pose to clinicians and geneticists interested in their pathogenesis, and proposes some method tools potentially useful in this research frame of reference.}, }
@article {pmid15530322, year = {2004}, author = {Areses Trapote, R and Urbieta Garagorri, MA and Ubetagoyena Arrieta, M and Mingo Monge, T and Arruebarrena Lizarraga, D}, title = {[Evaluation of renal stone disease: metabolic study].}, journal = {Anales de pediatria (Barcelona, Spain : 2003)}, volume = {61}, number = {5}, pages = {418-427}, doi = {10.1016/s1695-4033(04)78417-9}, pmid = {15530322}, issn = {1695-4033}, mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Kidney Calculi/chemistry/diagnosis/epidemiology/etiology/*metabolism ; Male ; Risk Factors ; }, abstract = {Renal stone formation is a multifactorial process in which all the information obtained from the patient (medical history, imaging tests, stone analysis, metabolic study and physicochemical urine analysis) shows a different facet of the same process. Consequently, all these investigations should be evaluated together. In half of all patients, stone formation is secondary to the presence of metabolic alterations in urine, of which the most frequent is idiopathic hypercalciuria. The second most frequent cause is infection and/or urinary malformations, while hereditary enzyme defects are highly unusual. Reference values for urinary excretion of lithogenic metabolites (calciuria, uricosuria, oxaluria, citraturia, etc.) are essential for an adequate metabolic study, since urinary excretion depends on multiple factors, which have been described in the various publications in the literature. Physicochemical study evaluating saturation of the various salts dissolved in urine should be performed. These saturations are currently considered to be a highly useful index for determining the risk of crystallization and stone formation in patients with lithiasis and for evaluating the effectiveness of treatment. Lastly, the metabolic profile of renal lithiasis in children resembles that in adults, suggesting that predisposition to renal lithiasis begins in childhood. The early detection of the metabolic alterations observed in these patients will reduce the incidence of this disease in both children and adults.}, }
@article {pmid15499217, year = {2004}, author = {Jaeger, P and Robertson, WG}, title = {Role of dietary intake and intestinal absorption of oxalate in calcium stone formation.}, journal = {Nephron. Physiology}, volume = {98}, number = {2}, pages = {p64-71}, doi = {10.1159/000080266}, pmid = {15499217}, issn = {1660-2137}, mesh = {Animals ; Calcium/*metabolism ; Calculi/*chemistry/*metabolism ; *Diet ; Humans ; Intestinal Absorption/*physiology ; Oxalates/*metabolism ; }, abstract = {The factors affecting the urinary excretion of oxalate are critical to the risk of forming calcium oxalate stones. This article reviews the role of dietary and intestinal oxalate in determining the level of oxalate excreted in urine. The amount of oxalate available for absorption throughout the intestine is highly dependent on the state of oxalate (a) in the food ingested, and (b) in the intestinal contents at each section of the intestinal tract since only the soluble form of oxalate can be absorbed. In this respect, the solubility of calcium oxalate (CaOx) under the prevailing conditions is paramount in determining the amount of oxalate available for absorption at any particular site. In turn, the main factors that control how much oxalate is in the soluble form are pH and the concentrations of calcium, magnesium and (indirectly) phosphate. Based on these parameters, a model of the intestine has been constructed which brings together the available evidence on the prevailing concentrations of these various factors at different sites in the intestine after allowing for dietary intake and the concentration of the above ions in intestinal secretions. The model then calculates the likely concentration of oxalate that is in the soluble form at each site and therefore available for passive absorption at that site. The model shows that oxalate is likely to be absorbed in the stomach, although it can be also absorbed in the small intestine, particularly at the distal end (after the absorption of calcium), and in the colon, since, on a normal intake of calcium and phosphate, most of the calcium in the large bowel would be anticipated to be precipitated as calcium phosphate under the prevailing alkaline conditions and high concentration of phosphate. The amount of free oxalate in the colon is also controlled by the presence or absence of Oxalobacter formigenes, an anaerobe that has an obligate requirement for oxalate as a source of energy and cellular carbon.}, }
@article {pmid15499216, year = {2004}, author = {Taylor, EN and Curhan, GC}, title = {Role of nutrition in the formation of calcium-containing kidney stones.}, journal = {Nephron. Physiology}, volume = {98}, number = {2}, pages = {p55-63}, doi = {10.1159/000080265}, pmid = {15499216}, issn = {1660-2137}, mesh = {Animals ; Calcium/*metabolism ; Humans ; Kidney Calculi/*chemistry/*pathology ; Nutritional Physiological Phenomena/*physiology ; }, abstract = {Diet plays an important role in the pathogenesis of calcium-containing kidney stones. Although much work has demonstrated that specific dietary components alter urinary composition and supersaturation, relatively few studies link the ingestion of these components with actual nephrolithiasis. This article reviews the dietary factors thought to promote or inhibit the formation of calcium stones and discusses the current controversies in the field of nutrition and nephrolithiasis. Special attention is paid to the roles of dietary calcium, supplemental calcium, oxalate, phytate, and n-3 fatty acids. We offer dietary recommendations to individuals who have suffered from a calcium-containing kidney stone, and emphasize that a patient's 24-hour urine chemistries should be used to help guide dietary intervention.}, }
@article {pmid15483460, year = {2004}, author = {Prié, D and Beck, L and Friedlander, G and Silve, C}, title = {Sodium-phosphate cotransporters, nephrolithiasis and bone demineralization.}, journal = {Current opinion in nephrology and hypertension}, volume = {13}, number = {6}, pages = {675-681}, doi = {10.1097/00041552-200411000-00015}, pmid = {15483460}, issn = {1062-4821}, mesh = {Animals ; Bone Demineralization, Pathologic/*physiopathology ; Calcium/metabolism ; Female ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors/metabolism ; Homeostasis/physiology ; Humans ; Kidney Calculi/*physiopathology ; Male ; Mice ; Phosphates/*metabolism ; Proton-Phosphate Symporters/metabolism ; Sodium-Potassium-Chloride Symporters/*metabolism ; }, abstract = {PURPOSE OF REVIEW: We discuss how recent findings obtained in disorders of phosphate metabolism in humans and in animal models have provided insights into the pathogenesis of renal stone formation and bone demineralization.<br><br>RECENT FINDINGS: Mice that are null for the sodium-phosphate cotransporter (NPT)2a gene (NPT2a(-/-) mice) exhibit hypophosphataemia, increased urinary phosphate excretion, hypercalciuria and nephrolithiasis, but no bone demineralization. Mice null for the sodium-hydrogen exchanger regulatory factor (NHERF)1 (NHERF1(-/-) mice) also exhibit hypophosphataemia and increased renal phosphate excretion with decreased renal NPT2a expression, but they present with a severe sex-dependent bone demineralization. Heterozygous loss-of-function mutations in the NPT2a gene in humans induce hypophosphataemia, increased urinary phosphate excretion, hypercalciuria, nephrolithiasis in males (to date) and bone demineralization of variable severity in both sexes. Patients and experimental animals with increased circulating levels of fibroblast growth factor 23 present with hypophosphataemia, increased urinary phosphate excretion, inappropriate calcitriol synthesis and rickets/osteomalacia, but no nephrolithiasis except when treated. Low-phosphate diet in spontaneously hypercalciuric rats and disruption of the 1-alpha-hydroxylase gene in NPT2a mice prevent renal stone formation.<br><br>SUMMARY: Increased urinary phosphate excretion is a risk factor for renal calcium stone formation when it is associated with hypercalciuria. As yet undefined interplay between NPT2a, NHERF1 and possibly other cotransporters or associated proteins in bone cells may account for the diversity of bone phenotypes observed in disorders of phosphate metabolism with impaired renal phosphate reabsorption. The pathogenesis of both renal stone and bone demineralization appear to be affected by species, sex and mutation type, among other factors.}, }
@article {pmid15332777, year = {2001}, author = {Naas, T and Al-Agili, S and Bashir, O}, title = {Urinary calculi: bacteriological and chemical association.}, journal = {Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit}, volume = {7}, number = {4-5}, pages = {763-770}, pmid = {15332777}, issn = {1020-3397}, mesh = {Academic Medical Centers ; Adolescent ; Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Bacterial Infections/*complications/epidemiology/metabolism/microbiology ; Calcium/analysis/metabolism ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Libya/epidemiology ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Phosphorus/analysis/metabolism ; Population Surveillance ; Risk Factors ; Sex Distribution ; Uric Acid/analysis/metabolism ; Urinalysis ; Urinary Calculi/*chemistry/epidemiology/metabolism/*microbiology ; Urinary Tract Infections/*complications/epidemiology/metabolism/microbiology ; }, abstract = {We investigated the bacteriology of urinary calculi in relation to urinary tract infection, stone formation, chemical composition and antibiotic sensitivity. Fifty-two patients (37 males, 15 females) with urolithiasis were studied. Urine, serum and urinary calculi specimens were taken and serum biochemical tests to detect uric acid, calcium and phosphorus were performed. Urine analysis and culture were also performed. Of the 52 patients, 19 (37%) had associated urinary tract infection, with Escherichia coli and Proteus mirabilis being the most common causative microorganisms. The bacterial isolates from urine and those from calculi differed in their susceptibility to antimicrobial agents. We conclude that in over 50% of patients with urolithiasis, urine culture can detect the infecting organisms associated with stone formation and the organisms within urinary calculi.}, }
@article {pmid15253454, year = {2004}, author = {Sommer, AP}, title = {Could reduced bone mineral densities in HIV be caused by nanobacteria?.}, journal = {Journal of proteome research}, volume = {3}, number = {3}, pages = {670-672}, doi = {10.1021/pr049978b}, pmid = {15253454}, issn = {1535-3893}, mesh = {Bacteria/*metabolism ; *Bone Density ; Calcium/metabolism ; HIV Infections/*metabolism ; Humans ; *Laser Therapy ; Peripheral Nervous System Diseases/*therapy ; Phosphates/metabolism ; }, abstract = {From the observations of different research groups reporting on reduced bone mineral density (BMD) and on a pronounced tendency for kidney stone formation, both in HIV-infected patients, and from results achieved in the treatment of severest peripheral neuropathy with lasers, it is concluded that nanobacteria (NB) could actively contribute to the reduction of BMD. A reduced BMD could primarily stem from NB, extracting calcium and phosphate from blood, affecting the calcium and phosphate homeostasis in humans.}, }
@article {pmid15247877, year = {2004}, author = {Ounadi-Corbillé, W and Brinkane, A and Benftima-Dutoya, S and Coblence, JF}, title = {[Nephrolithiasis and primary hyperarathyroidism in pregnancy].}, journal = {Annales d'endocrinologie}, volume = {65}, number = {2}, pages = {171-173}, doi = {10.1016/s0003-4266(04)95665-x}, pmid = {15247877}, issn = {0003-4266}, mesh = {Adult ; Female ; Humans ; Hyperparathyroidism/*diagnosis ; Infant, Newborn ; Kidney Calculi/*diagnosis/surgery ; Male ; Pregnancy ; Pregnancy Complications/*diagnosis ; Pregnancy Outcome ; }, abstract = {Diagnosis of hyperparathyroidism is unusual during pregnancy. The presence of a renal stone is a very exceptional finding. Hypercalcemia is often revealed by standard blood tests. We present here a clinical case of renal nephretic colic occurring during the third trimester of a fourth pregnancy. Our investigations led to the diagnosis of primary hyperparathyroidism which was successfully treated. Hyperparathyroidism during pregnancy is associated with a high incidence of fetal and maternal complications, essentially neonatal hypocalcemia. In utero death is rare but has been reported. Calcium metabolism during pregnancy is dependent on PTHrp. The surgical option is usually taken during the second trimester but can only be proposed during the third trimester in the event of medically resistant hypercalcemia.}, }
@article {pmid15221244, year = {2004}, author = {Nishiura, JL and Campos, AH and Boim, MA and Heilberg, IP and Schor, N}, title = {Phyllanthus niruri normalizes elevated urinary calcium levels in calcium stone forming (CSF) patients.}, journal = {Urological research}, volume = {32}, number = {5}, pages = {362-366}, pmid = {15221244}, issn = {0300-5623}, mesh = {Adult ; Brazil ; Calcium/blood/metabolism/*urine ; Citric Acid/urine ; Female ; Freeze Drying ; Humans ; Magnesium/urine ; Male ; Middle Aged ; Oxalates/urine ; *Phyllanthus ; Phytotherapy/*methods ; Plant Extracts/*therapeutic use ; Potassium/urine ; Prospective Studies ; Sodium/urine ; Uric Acid/urine ; Urinary Calculi/*drug therapy/urine ; }, abstract = {Phyllanthus niruri is a plant used for years in Brazil to treat urinary calculi. We prospectively evaluated the effect of P. niruri intake on 24 h urinary biochemical parameters in an attempt to assess its in vivo effect in calcium stone forming (CSF) patients. A total of 69 CSF patients (39 males and 30 females, 38+/-8 years old) were randomized to take either P. niruri (n=33) (450 mg capsules, td) or placebo (n=36) for 3 months. Blood calcium, uric acid, citrate, magnesium, oxalate, sodium and potassium were determined at baseline and at the end of the study. A subset analysis was made in patients classified according to the presence of metabolic abnormalities (hypercalciuria, hyperuricosuria, hyperoxaluria, hypocitraturia and hypomagnesiuria). Overall, there were no significant differences in the mean values of urinary parameters between the urine samples before and after P. niruri intake, except for a slight reduction in mean urinary magnesium after P. niruri, which was within the normal range. However, in the subset analysis, we observed that P. niruri induced a significant reduction in the mean urinary calcium in hypercalciuric patients (4.8+/-1.0 vs 3.4+/-1.1 mg/kg/24 h, P<0.05). In this short-term follow-up, no significant differences in calculi voiding and/or pain relief between the groups taking P. niruri or the placebo were detected. Our data suggest that P. niruri intake reduces urinary calcium based on the analysis of a subset of patients presenting with hypercalciuria. Larger trials including primary hypercalciuric stone formers should be performed in order to confirm these findings and to determine the possible clinical consequences of urinary calcium reduction during P. niruri administration.}, }
@article {pmid15211456, year = {2004}, author = {Shey, J and Cameron, MA and Sakhaee, K and Moe, OW}, title = {Recurrent calcium nephrolithiasis associated with primary aldosteronism.}, journal = {American journal of kidney diseases : the official journal of the National Kidney Foundation}, volume = {44}, number = {1}, pages = {e7-12}, doi = {10.1053/j.ajkd.2004.03.037}, pmid = {15211456}, issn = {1523-6838}, support = {M01-RR00633/RR/NCRR NIH HHS/United States ; P01-DK20543/DK/NIDDK NIH HHS/United States ; R01-DK48482/DK/NIDDK NIH HHS/United States ; T32 DK07257-23/DK/NIDDK NIH HHS/United States ; }, mesh = {Adrenal Gland Diseases/complications/diagnostic imaging ; Adrenal Glands/diagnostic imaging/pathology ; Adrenalectomy ; Calcium/metabolism ; Chronic Disease ; Citrates/metabolism ; Humans ; Hyperaldosteronism/*complications ; Hyperplasia/diagnostic imaging ; Hypertension/complications ; Hypokalemia/complications ; Kidney Calculi/chemistry/*etiology/prevention &amp; control ; Male ; Middle Aged ; Recurrence ; Tomography, X-Ray Computed ; }, abstract = {Typical manifestations of hyperaldosteronism include salt retention, hypokalemia, and metabolic alkalosis. However, a consequence infrequently recognized and described is hypocitraturia. In combination with hypercalciuria, aldosterone-induced hypocitraturia can trigger calcium nephrolithiasis. The authors report a case of an individual with primary hyperaldosteronism from an adrenal adenoma that resulted in hypocitraturia. The patient had severe recurrent renal calcium calculi that corrected with adrenalectomy. The clinical physiology of renal calcium and citrate handling in hyperaldosteronism is reviewed.}, }
@article {pmid15207250, year = {2004}, author = {Parody, TR and Stone, MJ}, title = {High level expression, activation, and antagonism of CC chemokine receptors CCR2 and CCR3 in Chinese hamster ovary cells.}, journal = {Cytokine}, volume = {27}, number = {1}, pages = {38-46}, doi = {10.1016/j.cyto.2004.03.013}, pmid = {15207250}, issn = {1043-4666}, support = {GM 55055/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Binding, Competitive ; CHO Cells ; Calcium/metabolism ; Chemokine CCL11 ; Chemokine CCL2/pharmacology/physiology ; Chemokine CCL26 ; Chemokines/*pharmacology/physiology ; Chemokines, CC/pharmacology/physiology ; Cricetinae ; Cricetulus ; Molecular Sequence Data ; Radioligand Assay ; Receptors, CCR2 ; Receptors, CCR3 ; Receptors, Chemokine/*agonists/*antagonists &amp; inhibitors/metabolism ; Sequence Alignment ; Structure-Activity Relationship ; }, abstract = {The specificity of leukocyte trafficking in inflammation is controlled by the interactions of chemokines with chemokine receptors. Reliable structure-function studies of chemokine-receptor interactions would benefit from cell lines that express consistent high levels of chemokine receptors. We describe herein two new Chinese hamster ovary (CHO) cell lines in which the genes for chemokine receptors CCR2 and CCR3 have been incorporated into identical positions in the host genome. CCR2 is the primary receptor for the chemokine monocyte chemoattractant protein-1 (MCP-1) whereas CCR3 is the primary receptor for the chemokines eotaxin-1, eotaxin-2 and eotaxin-3. Both receptors are expressed at >5,000,000 copies per cell, substantially higher levels than in previous cell lines, and both are competent for binding and activation by the cognate chemokines for these receptors. Using these cell lines we confirm that eotaxin-1 and eotaxin-3 can act as an agonist and an antagonist, respectively, of CCR2. In addition, we show that eotaxin-2 is an antagonist of CCR2 and MCP-1 is an agonist of CCR3. Comparison of the chemokine sequences reveals several positions that are identical in MCP-1 and eotaxin-1 but different in eotaxin-2 and eotaxin-3, suggesting that these amino acids play a role in CCR2 activation.}, }
@article {pmid15204429, year = {2004}, author = {Osther, PJ and Engel, K and Kildeberg, P}, title = {Renal response to acute acid loading--an organ physiological approach.}, journal = {Scandinavian journal of urology and nephrology}, volume = {38}, number = {1}, pages = {62-68}, doi = {10.1080/00365590310018838}, pmid = {15204429}, issn = {0036-5599}, mesh = {Acid-Base Equilibrium/physiology ; Acid-Base Imbalance/diagnosis/*prevention &amp; control ; Adaptation, Physiological ; Ammonium Chloride/*administration &amp; dosage/*pharmacokinetics ; Cross-Over Studies ; History, 16th Century ; Humans ; Hydrogen-Ion Concentration ; Kidney Function Tests ; Male ; Reference Values ; Risk Assessment ; Sensitivity and Specificity ; Urinalysis ; }, abstract = {OBJECTIVE: In previous studies of the renal response to acute NH4Cl acidosis no correlation was found between systemic acid-base status and the traditionally used quantity, renal net acid excretion (NAE). If NAE is to be considered a physiologically meaningful quantity then this is surprising, as the extracellular acid-base status would be expected to be the key physiological trigger for renal NAE. The object of this study was to investigate the renal response to acute non-carbonic acid loading using a quantitative organ physiological approach.<br><br>MATERIAL AND METHODS: Five-h NH4Cl loading studies were performed in 10 healthy men using a randomized, placebo-controlled, crossover design. Arterialized capillary blood, serum and urine were collected hourly during the loading studies for the measurement of electrolytes and acid-base status. Concentrations of non-metabolizable base (NB) and acid (NA) were calculated from measured concentrations of non-metabolizable ions according to Kildeberg.<br><br>RESULTS: In the steady state (placebo) the rate of renal excretion of NA (=-NB) was close to zero, indicating that the net extrarenal input of NA (endogeneous production, gastrointestinal absorption. skeletal release, etc.) was likewise about zero. An inverse correlation was found between blood pH and the rate of renal excretion of NA. Only a small amount of the acid load (approximately 8%) was excreted during the 5-h study period and this was accompanied by massive calciuria, indicating that mobilization of NB from bone contributed substantially to the current net extrarenal NA input.<br><br>CONCLUSION: From a physiological point of view, NB can be regarded as the actual substrate for renal acid-base control, and measurement of renal turnover of NB may give a more precise description of renal acid-base metabolism during acid loading than previously described methods.}, }
@article {pmid15149366, year = {2004}, author = {Floege, J}, title = {When man turns to stone: extraosseous calcification in uremic patients.}, journal = {Kidney international}, volume = {65}, number = {6}, pages = {2447-2462}, doi = {10.1111/j.1523-1755.2004.00664.x}, pmid = {15149366}, issn = {0085-2538}, mesh = {Calcinosis/diagnosis/*etiology/prevention &amp; control/therapy ; Calcium/metabolism ; Female ; Humans ; Male ; Middle Aged ; Phosphates/metabolism ; Risk Factors ; Tomography, X-Ray Computed ; Uremia/*complications ; }, }
@article {pmid15027893, year = {2004}, author = {Sayer, JA and Carr, G and Simmons, NL}, title = {Nephrocalcinosis: molecular insights into calcium precipitation within the kidney.}, journal = {Clinical science (London, England : 1979)}, volume = {106}, number = {6}, pages = {549-561}, doi = {10.1042/CS20040048}, pmid = {15027893}, issn = {0143-5221}, mesh = {Bartter Syndrome/complications ; Biological Transport/physiology ; Calcium/*metabolism ; Chemical Precipitation ; Humans ; Hyperoxaluria/complications ; Kidney/*metabolism ; Kidney Diseases/complications ; Kidney Medulla/metabolism ; Kidney Tubules/metabolism ; Nephrocalcinosis/*etiology/metabolism ; Oxalates/metabolism ; Phosphates/metabolism ; }, abstract = {Nephrocalcinosis may be defined as a generalized increase in the calcium content of the kidneys. This renal calcification may occur at a molecular, microscopic or macroscopic level leading to progressive amounts of renal damage. The major causes include those associated with an increase in urinary levels of calcium, oxalate and phosphate. Under these conditions, urine concentration and supersaturation leads to calcium crystal precipitation, which may be an intratubular event or initiate within the renal interstitium. The focus of discussion concerning renal calcification is often limited to factors that lead to renal stones (calculi and nephrolithiasis); however, nephrocalcinosis is a more sinister event, and often implies a serious metabolic defect. This review will discuss the hypotheses concerning initiating lesions of nephrocalcinosis using available laboratory and clinical studies and will examine whether new understanding of the molecular basis of tubulopathies, that lead to nephrocalcinosis, has given further insights.}, }
@article {pmid15015063, year = {2004}, author = {Alon, US and Zimmerman, H and Alon, M}, title = {Evaluation and treatment of pediatric idiopathic urolithiasis-revisited.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {19}, number = {5}, pages = {516-520}, pmid = {15015063}, issn = {0931-041X}, mesh = {Child ; Child, Preschool ; Diet ; Disease Progression ; Drinking ; Female ; Humans ; Male ; Patient Compliance ; Prospective Studies ; Surveys and Questionnaires ; Ultrasonography ; Urinary Calculi/diagnostic imaging/diet therapy/*therapy ; }, abstract = {The objective of the study was to update the evaluation and treatment of idiopathic urolithiasis in children in Western society. A secondary goal was to evaluate patients' compliance with high fluid intake. Over 2 years we prospectively studied children referred to us for idiopathic urolithiasis confirmed radiographically, excluding those with secondary disorders. A metabolic urinalysis, which included calcium, citrate, uric acid, oxalate, cystine, and creatinine, was ordered in all patients. Hypercalciuric patients were first treated with a low-sodium (Na)/high-potassium (K) diet and if hypercalciuria persisted, thiazides or potassium citrate was added. Follow-up ultrasound scans were scheduled every 10-12 months. Urine specific gravity (SG) measured during clinic visits was used to assess compliance with high fluid intake. A survey was sent to pediatric urologists and nephrologists to establish a recommended maximal SG value. Thirty healthy school-aged children served as controls. There were 45 children (24 males, 21 females) aged 10.4+/-2.0 years (median 11.0) studied. Stones were retrieved and analyzed in 28 showing calcium composition in all. Urine chemistry analysis was incomplete in 3, and in the others showed hypercalciuria in 33 (78.6%), hypocitraturia in 1 (2.4%), and normal values in 8 (19.0%). Treatment of 33 hypercalciuric patients consisted of diet alone in 13, potassium citrate in 17, thiazides in 2, and potassium citrate and thiazide in 1. All 33 achieved normocalciuria, apart from 2 who remained mildly hypercalciuric on diet alone. The 12 normocalciuric children were treated by diet modification alone. Follow-up ultrasonography showed no new stones in 36 of 39 patients. In 3, new stone formation was associated with recurrence of hypercalciuria after the potassium citrate dose was lowered or discontinued. Upon their first clinic visit, the urine SG of stone formers (1.021+/-0.007) was significantly higher than the maximum SG recommended by 18 physicians of 1.010+/-0.003 (P<0.001), and not different from the SG in the control group (1.018+/-0.007). Urine SG at follow-up visits was unchanged in stone formers. We therefore propose a step-wise approach in evaluating children with idiopathic urolithiasis in Western society, in which first only urine calcium is studied. Only if urine calcium is normal, should other chemistries be studied. In many hypercalciuric children, low-Na/high-K diet alone is effective, while in most others the addition of potassium citrate is well tolerated, normalizes calciuria, and protects against new stone formation. Children rarely comply with the recommendation of high fluid intake.}, }
@article {pmid14974568, year = {2004}, author = {Funaba, M and Uchiyama, A and Takahashi, K and Kaneko, M and Yamamoto, H and Namikawa, K and Iriki, T and Hatano, Y and Abe, M}, title = {Evaluation of effects of dietary carbohydrate on formation of struvite crystals in urine and macromineral balance in clinically normal cats.}, journal = {American journal of veterinary research}, volume = {65}, number = {2}, pages = {138-142}, doi = {10.2460/ajvr.2004.65.138}, pmid = {14974568}, issn = {0002-9645}, mesh = {Animals ; Calcium/metabolism ; *Cats ; Crystallization ; Dietary Carbohydrates/metabolism/*pharmacology ; Magnesium/metabolism ; Magnesium Compounds/metabolism/*urine ; Phosphates/metabolism/*urine ; Phosphorus/metabolism ; Struvite ; }, abstract = {OBJECTIVE: To evaluate effects of dietary carbohydrate on urine volume; struvite crystal formation; and calcium, phosphorus, and magnesium balance in clinically normal cats.<br><br>ANIMALS: 21 healthy adult cats (15 sexually intact males and 6 sexually intact females).<br><br>PROCEDURE: Diets containing no carbohydrate source (control diet), control plus starch, or control plus fiber were given in a 3 X 3 Latin-square design. The diets were available ad libitum in study 1 (n = 12) and given under restrictions in study 2 (9) to equalize daily intakes of crude protein among the 3 groups. Formation of struvite crystals and balance of calcium, phosphorus, and magnesium were measured.<br><br>RESULTS: Urine volume was lower in the starch group and fiber group in study 1, whereas no differences were detected among the groups in study 2. Urinary pH and struvite activity product were higher in the starch group in both studies, and the fiber group also had higher struvite activity product in study 2. In both studies, urinary concentrations of HCl-insoluble sediment were higher in the starch group and fiber group. In the fiber group, a net loss of body calcium, phosphorus, and magnesium was detected in study 2.<br><br>Starch and fiber in diets potentially stimulate formation of struvite crystals. Hence, reducing dietary carbohydrate is desirable to prevent struvite urolith formation. In addition, a net loss of body calcium, phosphorus, and magnesium during feeding of the fiber diet suggests that dietary inclusion of insoluble fiber could increase macromineral requirements of cats.}, }
@article {pmid14732909, year = {2003}, author = {Tosetto, E and Anglani, F and Graziotto, R and Citron, L and D'Angelo, A and Gambaro, G}, title = {[Dent's disease: hereditary nephrolithiasis related to defective tubular endocytosis processes].}, journal = {Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia}, volume = {20}, number = {6}, pages = {578-588}, pmid = {14732909}, issn = {0393-5590}, mesh = {Animals ; Calcium/metabolism ; Cells/ultrastructure ; Chloride Channels/analysis/physiology ; Endocytosis ; Fanconi Syndrome/complications/*genetics/metabolism/physiopathology ; Humans ; Kidney Calculi/etiology/*genetics/metabolism/physiopathology/therapy ; Kidney Tubules/*physiopathology ; Renal Insufficiency/etiology ; }, abstract = {Dent's disease, a X-linked hypercalciuric nephrolithiasis, is caused by mutations of the CLCN5 gene. The disease is characterised by low molecular weight proteinuria with variable presence of hypercalciuria, hyperphosphaturia, nephrocalcinosis, and kidney stones. CLCN5 encodes a chloride channel belonging to the voltage-gated chloride channel family, which is predominantly expressed in the endosomes of proximal tubular cells. By shunting the current of electrogenic H+-ATPase, ClC-5 is crucial for efficient acidification of renal endosomes. As shown in knock-out mouse models, the ClC-5 loss of function causes severe impairment of receptor-mediated endocytosis, as well as the endocytotic retrieval of plasma membrane proteins including megalin. In a minority of patients with classical Dent's disease, the analysis of CLCN5 coding sequences failed to identify causative mutations. It is conceivable that mutations in the 5' upstream regulatory regions could impair the correct processing and translation of CLCN5. The complexity of its promoter region seems to support this hypothesis. Molecular diagnosis of Dent's disease is now available; since the risk of developing renal insufficiency in adult life is elevated for this type of nephrolithiasis, the correct diagnosis could potentially modify the natural history of the disease by preventing the evolution towards uraemia.}, }
@article {pmid14729153, year = {2003}, author = {Wilson, RW and Grosell, M}, title = {Intestinal bicarbonate secretion in marine teleost fish-source of bicarbonate, pH sensitivity, and consequences for whole animal acid-base and calcium homeostasis.}, journal = {Biochimica et biophysica acta}, volume = {1618}, number = {2}, pages = {163-174}, doi = {10.1016/j.bbamem.2003.09.014}, pmid = {14729153}, issn = {0006-3002}, mesh = {Acid-Base Equilibrium ; Animals ; Bicarbonates/*metabolism ; Calcium/*metabolism ; Calcium Carbonate/metabolism ; Calcium Chloride ; Calcium Radioisotopes ; Carbon Dioxide/blood/metabolism ; Epithelium/metabolism ; Flounder/blood/*metabolism ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Intestinal Mucosa/*metabolism ; Perfusion ; Seawater ; }, abstract = {Whole animal studies using seawater European flounder (Platichthys flesus) revealed that increasing intestinal [Ca(2+)] to 20 mM stimulated net HCO(3)(-) base secretion by 57%, but this was effectively balanced by an increase in net acid secretion, likely from the gills, to maintain whole animal acid-base status. Higher Ca(2+) concentrations (40 and 70 mM) in ambient seawater resulted in reduced plasma total CO(2). This indicates (1) imperfect acid-base compensation, and (2) that endogenous metabolic CO(2) is insufficient to fuel intestinal HCO(3)(-) secretion, under hyper-stimulated conditions. Bicarbonate secretion plays an important role in preventing calcium absorption by precipitating a large fraction of the imbibed calcium as CaCO(3). Indeed, under high Ca(2+) conditions (20 mM), up to 75% of the intestinal Ca(2+) is precipitated as CaCO(3) and then excreted. This is undoubtedly important in protecting the marine teleost kidney from the need for excessive calcium excretion and risk of renal stone formation. Using an in vitro pH-stat technique with the isolated intestinal epithelium, the replacement of serosal CO(2) with a HEPES buffered saline had no effect on HCO(3)(-) secretion, indicating that the endogenous supply of HCO(3)(-) from CO(2) hydration within epithelial cells is adequate for driving baseline secretion rates. Further, in vitro data demonstrated a stimulatory effect of low pH on intestinal HCO(3)(-) secretion. Thus, both luminal Ca(2+) and H(+) can regulate HCO(3)(-) secretion but the precise mechanisms and their potential interaction are currently unresolved.}, }
@article {pmid14717005, year = {2003}, author = {Martola, L and Elinder, CG and Stenvinkel, P}, title = {[Why do patients with kidney diseases end up with a heart of stone? Disturbances in calcium-phosphate balance and chronic inflammation important causes].}, journal = {Lakartidningen}, volume = {100}, number = {50}, pages = {4180-4183}, pmid = {14717005}, issn = {0023-7205}, mesh = {Adult ; Calcinosis/*etiology/prevention &amp; control ; Calcium/metabolism ; Cardiomyopathies/*etiology/prevention &amp; control ; Cardiovascular Diseases/*etiology/prevention &amp; control ; Coronary Artery Disease/etiology/prevention &amp; control ; Homeostasis ; Humans ; Inflammation/complications/drug therapy ; Kidney Failure, Chronic/*complications/metabolism/therapy ; Phosphates/metabolism ; Renal Dialysis/adverse effects ; Risk Factors ; }, abstract = {Despite rapid improvement in dialysis technology during the last 20 years the mortality rate is still very high in patients with end-stage renal disease (ESRD), and is in fact comparable to that of many cancer patients with metastases. The main cause of mortality in ESRD is cardiovascular disease (CVD), and cardiac mortality for dialysis patients aged 45 years or younger is more than 100-fold greater than in the general population. Recent evidence suggests that the high cardiovascular mortality rate in this patient population is associated with extensive vascular and valvular calcification. Although hyperphosphatemia may be the major cause of vascular calcification in this patient group it has been suggested that chronic inflammation also contributes to this process. Indeed, recent evidence suggests that inflammatory mediators, such as pro-inflammatory cytokines and adipocytokines, may promote vascular calcification in vitro. Moreover, a2-Heremans Schmid glycoprotein (fetuin), an intrinsic inhibitor of the calcification process, is down-regulated during chronic inflammation. Lower levels of fetuin have recently been found to predict mortality in ESRD. Thus, further studies are needed to elucidate the roles of calcium-free phosphate binders as well as focused anti-inflammatory treatment strategies in the prevention of vascular and valvular calcification in ESRD.}, }
@article {pmid14670550, year = {2003}, author = {Moyad, MA}, title = {The potential benefits of dietary and/or supplemental calcium and vitamin D.}, journal = {Urologic oncology}, volume = {21}, number = {5}, pages = {384-391}, doi = {10.1016/s1078-1439(03)00108-x}, pmid = {14670550}, issn = {1078-1439}, mesh = {Adult ; Aged ; Calcium/metabolism/*therapeutic use ; Colonic Neoplasms/prevention &amp; control ; Diabetes Mellitus/prevention &amp; control ; *Dietary Supplements ; Humans ; Hypertension ; Kidney/metabolism ; Lipoproteins, HDL/metabolism ; Male ; Middle Aged ; Osteoporosis/metabolism ; Vitamin D/metabolism/*therapeutic use ; }, abstract = {Osteoporosis is a significant problem in women and men. In addition, as osteoporosis has garnered more attention there should be more attention than ever placed on the potential benefits of calcium and vitamin D. Clinicians need to inform patients that there are numerous healthy dietary sources of calcium and vitamin D. Calcium and vitamin D supplements seem to act synergistically to reduce fracture risk in men and women; therefore, they need to be taken together to impact fracture risk. In addition, almost every randomized trial of an effective osteoporosis drug therapy has utilized calcium and vitamin D to enhance the efficacy of the drug itself. Several forms of calcium supplements are commercially available today and clinicians need to understand the similarities and differences between them. Calcium and vitamin D in moderation also have a good safety profile and may actually have benefits far beyond osteoporosis therapy. For example, calcium may increase high-density lipoprotein (HDL), prevent colon polyps, reduce blood pressure, reduce kidney stone recurrence, and may promote weight loss. Vitamin D may reduce the risk of some cancers, provide an enhanced response to some chemotherapeutic agents, prevent type I diabetes, and may reduce tooth loss along with calcium. Clinicians need to encourage individuals to receive the recommended daily allowance of these two agents because they seem to have an impact on numerous health conditions besides osteoporosis.}, }
@article {pmid14663633, year = {2004}, author = {Lieske, JC and Farell, G and Deganello, S}, title = {The effect of ions at the surface of calcium oxalate monohydrate crystals on cell-crystal interactions.}, journal = {Urological research}, volume = {32}, number = {2}, pages = {117-123}, pmid = {14663633}, issn = {0300-5623}, support = {R01 DK 53399/DK/NIDDK NIH HHS/United States ; R21 DK 60707/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Calcium/metabolism/pharmacology ; Calcium Oxalate/*metabolism ; Carbon Radioisotopes ; Cell Adhesion/drug effects ; Cell Line ; Cell Survival/drug effects ; Crystallization ; Dogs ; Epithelial Cells/*drug effects/metabolism/ultrastructure ; Hydrogen-Ion Concentration ; Imaging, Three-Dimensional ; Ions/metabolism/*pharmacology ; Kidney/cytology ; Magnesium/metabolism/pharmacology ; Microscopy, Electron, Scanning ; Microscopy, Fluorescence ; Time Factors ; }, abstract = {Magnesium is an abundant ion in biologic systems, including renal tubular fluid; however, the precise role of magnesium during the interaction of calcium oxalate crystals with cells has not been previously defined. In addition, the respective roles of calcium and hydrogen ions during the cell-crystal bonding interaction remain poorly defined. Here we report an atomic level three-dimensional study of a single crystal of calcium oxalate monohydrate (COM; whewellite) which was bathed in a solution of magnesium hexahydrate for 1 year. Magnesium was not incorporated into the structure of whewellite to any significant degree. Instead, COM accepted magnesium primarily as an adsorbate in a binding configuration which, as a surface phenomenon, is controlled by localized charge effects. The effect of magnesium and calcium on the efficiency of calcium oxalate crystal binding to renal cells was also investigated. When present in supraphysiologic concentrations (greater than 0.1 M), magnesium progressively inhibited adhesion of pre-formed COM crystals to cultured renal cells. Therefore, even though magnesium does not incorporate into the crystal structure of calcium oxalate, magnesium can exert important surface effects and change the interaction of pre-formed COM with molecules anchored on the cell surface. Similarly, binding was nearly blocked when the exogenous calcium concentration was > or =0.1 M (supraphysiologic range), although in lower concentrations (within the physiologic range) exogenous calcium promoted crystal adhesion. Finally, the ambient hydrogen ion concentration also influenced calcium oxalate crystal interactions with renal cells, with maximal binding occurring at a pH of 4. Therefore, hypercalciuria and/or an acidic urine could each promote renal stone formation via increased crystal adhesion to renal cells, a previously under-appreciated potential mechanism.}, }
@article {pmid14638914, year = {2003}, author = {Asselman, M and Verhulst, A and De Broe, ME and Verkoelen, CF}, title = {Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured/regenerating tubular epithelial cells in rat kidneys.}, journal = {Journal of the American Society of Nephrology : JASN}, volume = {14}, number = {12}, pages = {3155-3166}, doi = {10.1097/01.asn.0000099380.18995.f7}, pmid = {14638914}, issn = {1046-6673}, mesh = {Adhesiveness ; Animals ; Calcium/metabolism ; Calcium Oxalate/*metabolism ; Crystallization ; Hyaluronan Receptors/*biosynthesis ; Hyaluronic Acid/*biosynthesis ; Kidney/*physiology ; Kidney Tubules/cytology/pathology ; Male ; Osteopontin ; Rats ; Rats, Wistar ; *Regeneration ; Sialoglycoproteins/*biosynthesis ; Urothelium/cytology ; }, abstract = {Retention of crystals in the kidney is an essential early step in renal stone formation. Studies with renal tubular cells in culture indicate that hyaluronan (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an important role in calcium oxalate (CaOx) crystal binding during wound healing. This concept was investigated in vivo by treating rats for 1, 4, and 8 d with ethylene glycol (0.5 and 0.75%) in their drinking water to induce renal tubular cell damage and CaOx crystalluria. Tubular injury was morphologically scored on periodic acid-Schiff-stained renal tissue sections and tissue repair assessed by immunohistochemical staining for proliferating cell nuclear antigen. CaOx crystals were visualized in periodic acid-Schiff-stained sections by polarized light microscopy, and renal calcium deposits were quantified with von Kossa staining. HA was visualized with HA-binding protein and OPN and CD44 immunohistochemically with specific antibodies and quantified with an image analyzer system. Already after 1 d of treatment, both concentrations of ethylene glycol induced hyperoxaluria and CaOx crystalluria. At this point, there was neither tubular injury nor crystal retention in the kidney, and expression of HA, OPN, and CD44 was comparable to untreated controls. After 4 and 8 d of ethylene glycol, however, intratubular crystals were found adhered to injured/regenerating (proliferating cell nuclear antigen positive) tubular epithelial cells, expressing HA, OPN, and CD44 at their luminal membrane. In conclusion, the expression of HA, OPN, and CD44 by injured/regenerating tubular cells seems to play a role in retention of crystals in the rat kidney.}, }
@article {pmid14555462, year = {2004}, author = {Brown, DM and Donaldson, K and Borm, PJ and Schins, RP and Dehnhardt, M and Gilmour, P and Jimenez, LA and Stone, V}, title = {Calcium and ROS-mediated activation of transcription factors and TNF-alpha cytokine gene expression in macrophages exposed to ultrafine particles.}, journal = {American journal of physiology. Lung cellular and molecular physiology}, volume = {286}, number = {2}, pages = {L344-53}, doi = {10.1152/ajplung.00139.2003}, pmid = {14555462}, issn = {1040-0605}, mesh = {Acetylcysteine/*analogs &amp; derivatives/pharmacology ; Air Pollutants/immunology/*pharmacology ; Animals ; Calcium/*metabolism ; Calcium Channel Blockers/pharmacology ; Calcium Signaling/drug effects/immunology ; Carbon/immunology/pharmacology ; Chelating Agents/pharmacology ; Egtazic Acid/*analogs &amp; derivatives/pharmacology ; Gene Expression/immunology ; Lysine/*analogs &amp; derivatives/pharmacology ; Macrophages, Alveolar/immunology/*metabolism ; Male ; Particle Size ; RNA, Messenger/analysis ; Rats ; Rats, Wistar ; Reactive Oxygen Species/immunology/*metabolism ; Transcription Factor AP-1/*metabolism ; Tumor Necrosis Factor-alpha/*genetics/metabolism ; Verapamil/pharmacology ; }, abstract = {Ultrafine (Uf) particles are a component of particulate air pollution suggested to be responsible for the health effects associated with elevations of this pollutant. We have previously suggested that Uf particles, through the induction of oxidative stress, may induce inflammation in the lung, thus exacerbating preexisting illness in susceptible individuals. Alveolar macrophages are considered to play a key role in particlemediated inflammation and lung disease. The effect of Uf particles on rat alveolar macrophages and human blood monocytes was investigated with reference to the roles of calcium and reactive oxygen species (ROS). TNF-alpha protein release, intracellular calcium concentration, TNF-alpha mRNA expression, and transcription factor activation were studied as end points after treatment of rat alveolar macrophages or peripheral blood monocytes. The calcium channel blocker verapamil, the intracellular calcium chelator BAPTA-AM, the calmodulin inhibitor W-7, and the antioxidants Trolox and Nacystelin (NAL) were included in combination with Uf particles. Verapamil reduced intracellular calcium concentration in rat alveolar macrophages on stimulation with Uf particles. This effect was also apparent with transcription factor AP-1 activation. All antagonists and antioxidants reduced Uf-stimulated nuclear localization of the p50 and p65 subunits of NF-kappaB in human monocytes. Verapamil, BAPTA-AM, and NAL reduced Uf-stimulated TNF-alpha protein release, whereas only verapamil reduced Uf-stimulated mRNA expression in rat alveolar macrophages. In human monocytes, verapamil, Trolox, BAPTA-AM, and W-7 reduced Uf-stimulated TNF-alpha protein release. These findings suggest that Uf particles may exert proinflammatory effects by modulating intracellular calcium concentrations, activation of transcription factors, and cytokine production through a ROS-mediated mechanism.}, }
@article {pmid12840072, year = {2