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22 Jan 2021 at 01:35
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Bibliography on: Calcium Metabolism and Urinary Stones


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RJR: Recommended Bibliography 22 Jan 2021 at 01:35 Created: 

Calcium Metabolism and Urinary Stones

Wikipedia: Calcium Metabolism — everybody knows that osteoporosis is a huge threat and that the best way to reduce the risk of osteoporosis is to take lots of dietary calcium supplements and vitamin D pills.

OK, exercise is good, too, but that can involve actually breaking a sweat — something that not everyone wants to do.

But, did you also know that hypercalciuria (too much secreted calcium in the urine) is associated with a significant increase in the risk for kidney stones? And, you can easily get hypercalciuria if you pop too many calcium-supplement pills. Hmmmm. Nice choice, break a hip or pass kidney stones... What to do? As with most things biological, reality lies somewhere in the trade-off zone. A quick look at the literature dealing with calciuria and kidney stones is one way to start.

Created with PubMed® Query: (calciuria OR "calcium metabolism") AND (urolith or "kidney stone" or "kidney stones" or "bladder stones" or stones) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2021-01-09

Charles PY, Letavernier E, Périé S, et al (2021)

Effect of parathyroidectomy on renal stone recurrence.

Urolithiasis [Epub ahead of print].

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.

RevDate: 2021-01-09

Keller EX, De Coninck V, Pietropaolo A, et al (2021)

Metabolic Evaluation: Place of the Calcium Load Test: How, When, For Whom, and Why?.

European urology focus pii:S2405-4569(20)30321-7 [Epub ahead of print].

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.

RevDate: 2020-12-30

Litvinova MM, Filippova TV, Khafizov KF, et al (2020)

[A complicated case of calcium urolithiasis in a carrier of SLC7A9 gene mutation responsible for cystinuria].

Urologiia (Moscow, Russia : 1999).

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.

RevDate: 2020-10-13

Aoun B, Sanjad S, Degheili JA, et al (2020)

Kidney and Metabolic Phenotypes in Glycogen Storage Disease Type-I Patients.

Frontiers in pediatrics, 8:591.

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.

RevDate: 2020-10-20

Milart J, Lewicka A, Jobs K, et al (2020)

Effect of Vitamin D Treatment on Dynamics of Stones Formation in the Urinary Tract and Bone Density in Children with Idiopathic Hypercalciuria.

Nutrients, 12(9):.

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.

RevDate: 2020-10-05

Zhou Y, EE Lower (2020)

Balancing Altered Calcium Metabolism with Bone Health in Sarcoidosis.

Seminars in respiratory and critical care medicine, 41(5):618-625.

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.

RevDate: 2020-12-07

Irzyniec T, Boryń M, Kasztalska J, et al (2020)

The effect of an oral sodium phosphate load on parathyroid hormone and fibroblast growth factor 23 secretion in normo- and hypercalciuric stone-forming patients.

Clinical nutrition (Edinburgh, Scotland), 39(12):3804-3812.

BACKGROUND & 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).

METHODS: Sodium phosphates NaH2PO4/Na2HPO4-100mmol were administered orally for five days in 19 hypercalciuric [urinary Ca(U-Ca) 6.5 ± 1.7 mmol/d]-HSF, 35 normocalciuric (2.5±1 mmol/d)-NSF stone-forming patients and 19 controls (U-Ca 2.5 ± 1.4 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.

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 ± 605vs766 ± 315 p = 0.0457) and fifth days (1211 ± 641vs777 ± 299 p = 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 ± 401vs835 ± 220 p = 0.0341).

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.

RevDate: 2020-06-22

Islam AK, Holt S, Reisch J, et al (2020)

What Predicts Recurrent Kidney Stone after Parathyroidectomy in Patients with Primary Hyperparathyroidism?.

Journal of the American College of Surgeons, 231(1):74-82.

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.

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.

RESULTS: Mean age at parathyroidectomy was 57 ± 14 years. Pre-parathyroidectomy, mean serum calcium, 24-hour urine calcium, and PTH were 10.6 ± 0.5 mg/dL, 378 ± 209 mg/day, and 114 ± 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 ± 1.6 years after parathyroidectomy. Patients with recurrent KSD post-parathyroidectomy were significantly younger compared with patients without recurrent KSD (51 ± 15 vs 60 ± 13 years, p = 0.02). In a logistic regression model, younger age remains a strong predictive factor for recurrent KSD.

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.

RevDate: 2020-06-30

Bayomy O, Zaheer S, Williams JS, et al (2020)

Disentangling the Relationships Between the Renin-Angiotensin-Aldosterone System, Calcium Physiology, and Risk for Kidney Stones.

The Journal of clinical endocrinology and metabolism, 105(6):.

CONTEXT: Complex relationships between aldosterone and calcium homeostasis have been proposed.

OBJECTIVE: To disentangle the influence of aldosterone and intravascular volume on calcium physiology.

DESIGN: Patient-oriented and epidemiology studies.

SETTING: Clinical research center and nationwide cohorts.

PARTICIPANTS/INTERVENTIONS: Patient-oriented study (n = 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 = 3755): the association between 24h urinary sodium and calcium excretion and risk for kidney stones was assessed.

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 < 0.001) and plasma aldosterone (LIB: 2.0 [2.0, 2.7] vs. RES: 20.0 [16.1, 31.0] vs. ng/dL; P < 0.001), but increased calciuria (LIB: 238.4 ± 112.3 vs. RES: 112.9 ± 60.8 mg/24hr; P < 0.0001) and decreased serum calcium (LIB: 8.9 ± 0.3 vs. RES: 9.8 ± 0.4 mg/dL; P < 0.0001). Epidemiology study: mean urinary calcium excretion was higher with greater urinary sodium excretion. Compared to a urinary sodium excretion of < 120 mEq/day, a urinary sodium excretion of ≥220 mEq/day was associated with a higher risk for having kidney stones in women (risk ratio = 1.79 [95% confidence interval 1.05, 3.04]) and men (risk ratio = 2.06 [95% confidence interval 1.27, 3.32]).

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.

RevDate: 2020-02-20
CmpDate: 2020-02-20

Spivacow FR, Pailler M, P Martínez (2019)

[Idiopathic hypercalciuria: can the diuretics be avoided?].

Medicina, 79(6):477-482.

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.

RevDate: 2020-06-18

De Ruysscher C, Pien L, Tailly T, et al (2020)

Risk factors for recurrent urolithiasis in children.

Journal of pediatric urology, 16(1):34.e1-34.e9.

PURPOSE: To identify risk factors associated with recurrent kidney stones in a paediatric cohort in a Belgian tertiary centre.

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.

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) > 85th percentile and asymptomatic stones at initial presentation were associated with 1.8 and 0.1 times lower risk of recurrent stones, respectively (p = 0.020, 95% confidence interval (CI):0.368-8.749 and p = 0.017, 95% CI:0.014-0.921). In contrast, immobilization resulted in a 10-times higher risk (p = 0.002, 95% CI:1.968-50.005) and the need for technical intervention was associated with a 3.2- times higher risk (p = 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 = 0.030, 95% CI:0.006-0.739).

DISCUSSION: A possible explanation of reduced risk in patients with a BMI > 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 the entire paediatric population.

CONCLUSION: Of all the factors investigated in our cohort, BMI >85 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.

RevDate: 2020-08-13
CmpDate: 2020-08-13

Roche EC, Redmond EJ, Yap LC, et al (2019)

Seasonal Variation in the Frequency of Presentation with Acute Ureteral Colic and Its Association with Meteorologic Factors.

Journal of endourology, 33(12):1046-1050.

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.

RevDate: 2020-01-10
CmpDate: 2020-01-10

Schöfl C (2019)

[Update - Calcium Metabolism].

Deutsche medizinische Wochenschrift (1946), 144(16):1125-1132.

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.

RevDate: 2020-10-01
CmpDate: 2020-01-15

Bejan CA, Lee DJ, Xu Y, et al (2019)

Performance of a Natural Language Processing Method to Extract Stone Composition From the Electronic Health Record.

Urology, 132:56-62.

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.

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.

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 = 87.5%). Survival analysis from a second stone surgery showed statistically significant differences among stone types (P = .03). Several phenotype associations were found: uric acid-type 2 diabetes (odds ratio, OR = 2.69, 95% confidence intervals, CI = 1.91-3.79), struvite-neurogenic bladder (OR = 12.27, 95% CI = 4.33-34.79), struvite-urinary tract infection (OR = 7.36, 95% CI = 3.01-17.99), hydroxyapatite-pulmonary collapse (OR = 3.67, 95% CI = 2.10-6.42), hydroxyapatite-neurogenic bladder (OR = 5.23, 95% CI = 2.05-13.36), brushite-calcium metabolism disorder (OR = 4.59, 95% CI = 2.14-9.81), and brushite-hypercalcemia (OR = 4.09, 95% CI = 1.90-8.80).

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.

RevDate: 2020-07-15
CmpDate: 2020-01-06

Cairoli E, Eller-Vainicher C, Morlacchi LC, et al (2019)

Bone involvement in young adults with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure.

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 30(6):1255-1263.

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.

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.

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 ± 8.4 years) consecutively referred as lung transplant candidates.

RESULTS: Mean 25OHVitD levels (54.9 ± 26.2 nmol/L) were below the reference range and hypovitaminosis D (25OHVitD < 75 nmol/L) was found in 34 patients (81%) and daily calcium intakes (median 550 mg/day) were lower than recommended. A BMD below the expected range for age (Z-score of - 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 = 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 < 0.05) and 25OHVitD levels (p < 0.01).

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.

RevDate: 2019-05-09
CmpDate: 2019-05-09

Filippova TV, Litvinova MM, Rudenko VI, et al (2018)

[Genetic factors for monogenic forms of calcium urolithiasis].

Urologiia (Moscow, Russia : 1999).

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.

RevDate: 2020-01-28
CmpDate: 2020-01-28

Rimer JD, Sakhaee K, NM Maalouf (2019)

Citrate therapy for calcium phosphate stones.

Current opinion in nephrology and hypertension, 28(2):130-139.

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.

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.

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.

RevDate: 2020-09-28

Idrees N, Tabassum B, Abd Allah EF, et al (2018)

Groundwater contamination with cadmium concentrations in some West U.P. Regions, India.

Saudi journal of biological sciences, 25(7):1365-1368.

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.

RevDate: 2019-04-05
CmpDate: 2019-03-05

David K, Moyson C, Vanderschueren D, et al (2019)

Long-term complications in patients with chronic hypoparathyroidism: a cross-sectional study.

European journal of endocrinology, 180(1):71-78.

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.

RevDate: 2018-12-21
CmpDate: 2018-12-21

Raynor WY, Al-Zaghal A, Werner TJ, et al (2018)

18F-NaF PET/CT in Prostatic Calculi.

Clinical nuclear medicine, 43(12):e484-e485.

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.

RevDate: 2018-11-14
CmpDate: 2018-09-17

Letavernier E, M Daudon (2018)

Vitamin D, Hypercalciuria and Kidney Stones.

Nutrients, 10(3):.

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.

RevDate: 2019-11-13
CmpDate: 2017-12-14

Egshatyan LV, NG Mokrysheva (2017)

[Calciuria as a metabolic marker for various conditions and diseases].

Urologiia (Moscow, Russia : 1999).

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.

RevDate: 2018-03-30
CmpDate: 2018-03-30

Bilezikian JP, Bandeira L, Khan A, et al (2018)


Lancet (London, England), 391(10116):168-178.

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.

RevDate: 2018-08-07
CmpDate: 2018-08-07

Spivacow FR, C Palumbo (2017)

[Asymptomatic primary hyperparathyroidism in women].

Medicina, 77(3):196-200.

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.

RevDate: 2019-01-10
CmpDate: 2018-09-10

Rodgers AL, Jappie-Mahomed D, PJ van Jaarsveld (2018)

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.

Urolithiasis, 46(2):137-147.

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.

RevDate: 2018-12-31
CmpDate: 2018-02-20

Ure ME, Heydari E, Pan W, et al (2017)

A variant in a cis-regulatory element enhances claudin-14 expression and is associated with pediatric-onset hypercalciuria and kidney stones.

Human mutation, 38(6):649-657.

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.

RevDate: 2018-12-02
CmpDate: 2017-06-09

Malihi Z, Wu Z, Stewart AW, et al (2016)

Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis.

The American journal of clinical nutrition, 104(4):1039-1051.

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.

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 ≥24 wk compared with in subjects in the placebo arm.

DESIGN: The following 3 main online databases were searched: Ovid Medline (PubMed), EMBASE, and the Cochrane Library. Software was used for the meta-analysis.

RESULTS: A total of 48 studies with 19,833 participants were identified, which reported ≥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.

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.

RevDate: 2018-12-02
CmpDate: 2017-10-19

Vitale C, Bermond F, Rodofili A, et al (2016)

[The effects of Cinacalcet in renal stone formers with primary hyperparathyroidism].

Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia, 33(4):.

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.

RevDate: 2018-11-13
CmpDate: 2017-12-11

Vezzoli G, Macrina L, Rubinacci A, et al (2016)

Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones.

Clinical journal of the American Society of Nephrology : CJASN, 11(8):1450-1455.

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.

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.

RESULTS: Serum strontium concentration-time curve (P<0.001) and strontium clearance (4.9±1.3 versus 3.5±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±3.4 ml/min) than in hypercalciuric stone formers and HNSFs with low bone mineral density (3.6±2.5 and 3.1±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).

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.

RevDate: 2016-04-12
CmpDate: 2016-07-19

Arrabal-Polo MÁ, del Carmen Cano-García M, M Arrabal-Martín (2016)

[The fasting calcium/creatinine ratio in patients with calcium stones and the relation with hypercalciuria and phosphocalcium metabolism].

Archivos espanoles de urologia, 69(3):117-120.

OBJECTIVE: To determine the importance of fasting calcium/creatinine ratio in patients with calcium stones and its relation with hypercalciuria and phospho-calcium metabolism.

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≤0.05.

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).

CONCLUSION: Increased fasting calcium/creatinine determines increased 24 hours calcium excretion, although the sensitivity and specificity to determine hypercalciuria is not high.

RevDate: 2018-05-16
CmpDate: 2017-07-03

Moor MB, O Bonny (2016)

Ways of calcium reabsorption in the kidney.

American journal of physiology. Renal physiology, 310(11):F1337-50.

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.

RevDate: 2017-01-03
CmpDate: 2016-11-04

Pramono LA, Larasati D, Yossy Y, et al (2015)

Recurrent Bilateral Staghorn Stones as a Manifestation of Primary Hyperparathyroidism due to Parathyroid Adenoma.

Acta medica Indonesiana, 47(4):348-351.

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.

RevDate: 2018-12-02
CmpDate: 2017-09-05

Arrabal-Martín M, González-Torres S, Cano-García MC, et al (2016)

Treatment with hydrochlorothiazide and alendronate in patients with stones and bone mineral density loss. Evolution of bone metabolism and calciuria with medical treatment.

Archivos espanoles de urologia, 69(1):9-18.

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.

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.

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 Β-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 Β-crosslaps decrease. However, in group 2 the decrease in urinary calcium and calcium/creatinine was more significant than in group 1.

CONCLUSION: Treatment with thiazide decrease calciuria and produces an improvement in bone mineral density, although not in the same range as treatment with alendronate.

RevDate: 2016-10-20
CmpDate: 2015-11-17

Prezioso D, Strazzullo P, Lotti T, et al (2015)

Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group.

Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica, 87(2):105-120.

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.

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.

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.

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 ≥ 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.

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.

RevDate: 2020-09-30
CmpDate: 2015-06-18

Rull MA, Cano-García Mdel C, Arrabal-Martín M, et al (2015)

The importance of urinary calcium in postmenopausal women with osteoporotic fracture.

Canadian Urological Association journal = Journal de l'Association des urologues du Canada, 9(3-4):E183-6.

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.

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 ≤ 0.05.

RESULTS: The mean age was 70.1 ± 13.8 in Group 1 and 56.7 ± 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.

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.

RevDate: 2015-06-02
CmpDate: 2016-09-22

Ubetagoyena Arrieta M, Corera Casty MN, Martínez Saenz de Jubera J, et al (2015)

[Risk assessment in children with lithogenic kidney stones].

Archivos espanoles de urologia, 68(4):429-434.

OBJECTIVE: The aim of this study was to describe the lithogenic risk profile of pediatric patients with lithiasis.

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.

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).

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.

RevDate: 2016-02-19
CmpDate: 2015-10-01

Palmieri S, Eller-Vainicher C, Cairoli E, et al (2015)

Hypercalciuria May Persist After Successful Parathyroid Surgery and It Is Associated With Parathyroid Hyperplasia.

The Journal of clinical endocrinology and metabolism, 100(7):2734-2742.

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.

OBJECTIVE: The purpose of this study was to determine the prevalence of cRL in our 1HPT population and investigate cRL-related factors.

DESIGN: This was a retrospective longitudinal study.

SETTING: The study was conducted in an outpatient setting.

PATIENTS/INTERVENTION: The participants were 95 patients with 1HPT successfully operated on who had a normal estimated glomerular filtration rate.

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.

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 ± 0.6 vs 11.4 ± 0.8 mg/dL [2.7 ± 0.2 vs 2.8 ± 0.2 mmol/L], P = .01 and 2.6 ± 0.5 vs 2.4 ± 0.4 mg/dL [0.84 ± 0.2 vs 0.77 ± 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).

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.

RevDate: 2015-03-03
CmpDate: 2015-05-04

Hartman C, Friedlander JI, Moreira DM, et al (2015)

Does hypertension impact 24-hour urine parameters in patients with nephrolithiasis?.

Urology, 85(3):539-543.

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.

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.

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 <.05) in patients with HTN. Multivariate analysis showed significantly lower calcium, citrate, and SS CaOx in patients with HTN (all P <.05).

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.

RevDate: 2018-08-13
CmpDate: 2017-02-17

Ochoa-Hortal Rull MÁ, Cano-García MC, Arrabal Martín M, et al (2015)

Calcium and phosphorus metabolism and lithogenic factors in patients with osteoporotic fracture.

Actas urologicas espanolas, 39(5):279-282.

OBJECTIVES: To demonstrate the attendance of mineral metabolism disorders and lithogenic factors in patients' urine with osteoporotic fracture without previously known stones

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.

RESULTS: 12 men and 55 women with mean age 68.8±14.5 years old were included. Mean Body Mass Index (BMI) was 27.4±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.

CONCLUSIONS: Patients with osteoporotic fractures show different lithogenic factors in urine, mainly hypercalciuria, always in fasting conditions.

RevDate: 2018-11-13
CmpDate: 2015-12-04

Arrabal-Martin M, Poyatos-Andujar A, Cano-García Mdel C, et al (2015)

The importance of calciuria as lithogenic factors in patients with osteopenia/osteoporosis.

International urology and nephrology, 47(3):445-449.

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.

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 ≤ 0.05 was considered statistically significant.

RESULTS: Patients in Group 2 presented greater loss of bone mineral density and more elevated alkaline phosphatase, iPTH, phosphorous and β-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 β-crosslaps levels are risk factors for bone mineral density loss, while low urinary calcium excretion was protective against bone demineralization.

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.

RevDate: 2016-11-25
CmpDate: 2015-02-17

Figueres ML, Linglart A, Bienaime F, et al (2015)

Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 65(1):122-126.

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.

RevDate: 2018-11-13
CmpDate: 2016-01-13

Dorairajan N, PV Pradeep (2014)

Vignette hyperparathyroidism: glimpse into its history.

International surgery, 99(5):528-533.

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.

RevDate: 2017-09-12
CmpDate: 2016-07-14

Balestracci A, Meni Battaglia L, Toledo I, et al (2014)

Idiopathic hypercalciuria in children with urinary tract infection.

Archivos argentinos de pediatria, 112(5):428-433.

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.

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.

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).

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.

RevDate: 2020-10-01
CmpDate: 2016-01-28

Nouvenne A, Ticinesi A, Morelli I, et al (2014)

Fad diets and their effect on urinary stone formation.

Translational andrology and urology, 3(3):303-312.

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.

RevDate: 2014-09-05
CmpDate: 2015-06-09

Xie R, Tang B, Yong X, et al (2014)

Roles of the calcium sensing receptor in digestive physiology and pathophysiology (review).

International journal of oncology, 45(4):1355-1362.

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.

RevDate: 2019-11-12
CmpDate: 2016-06-23

Ramos MF, de Santana LG, Rasvickas CV, et al (2014)

Effect of vitamin D₃ overdose and calcium supplementation in experimental nephrolithiasis model.

Jornal brasileiro de nefrologia : 'orgao oficial de Sociedades Brasileira e Latino-Americana de Nefrologia, 36(2):132-138.

INTRODUCTION: There is little information in the literature relating supplementary oral usage of vitamin D and calcium to the development of kidney stones.

OBJECTIVE: To evaluate the effect of high dose, 200 IU of vitamin D3 (V) with calcium supplementation (Ca).

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.

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).

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.

RevDate: 2014-03-21
CmpDate: 2014-04-07

Dzerganov NK, Egshatian LV, Mokrysheva NG, et al (2013)

[Clinical and laboratory parameters in patients with urolithiasis in the presence and absence of primary hyperparathyroidism].

Urologiia (Moscow, Russia : 1999).

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.

RevDate: 2020-09-29
CmpDate: 2016-03-09

Grases F, Costa-Bauzá A, Prieto RM, et al (2014)

Internalization of Calcium Oxalate Calculi Developed in Narrow Cavities.

Urology case reports, 2(2):51-53.

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.

RevDate: 2018-12-21
CmpDate: 2014-10-08

Escribano J, Balaguer A, Roqué i Figuls M, et al (2014)

Dietary interventions for preventing complications in idiopathic hypercalciuria.

The Cochrane database of systematic reviews.

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.

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.

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.

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.

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).

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 µmol/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.

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.

RevDate: 2016-11-25
CmpDate: 2014-10-28

Kirejczyk JK, Porowski T, Filonowicz R, et al (2014)

An association between kidney stone composition and urinary metabolic disturbances in children.

Journal of pediatric urology, 10(1):130-135.

OBJECTIVE: To determine kidney stone composition in children and to correlate stone fractions with urinary pH and metabolic urinary risk factors.

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.

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.

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.

RevDate: 2019-11-12
CmpDate: 2013-09-03

Joshi A, Gupta SK, A Srivastava (2013)

Metabolic evaluation in first-time renal stone formers in North India: a single center study.

Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia, 24(4):838-843.

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.

RevDate: 2018-11-13
CmpDate: 2013-03-26

Arrabal-Polo MA, Arrabal-Martin M, S Arias-Santiago (2013)

Bone and metabolic markers in women with recurrent calcium stones.

Korean journal of urology, 54(3):177-182.

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.

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.

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.

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.

RevDate: 2015-11-19
CmpDate: 2014-07-31

Arrabal-Polo MÁ, Sierra Girón-Prieto M, Orgaz-Molina J, et al (2013)

Calcium renal lithiasis and bone mineral density. Importance of bone metabolism in urinary lithiasis.

Actas urologicas espanolas, 37(6):362-367.

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.

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.

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.

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 β-CrossLaps are determinant of nephrolithiasis and mineral density loss in these patients.

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.

RevDate: 2013-11-21
CmpDate: 2013-06-17

Arrabal-Polo MA, Arias-Santiago S, de Haro-Muñoz T, et al (2013)

Effects of aminobisphosphonates and thiazides in patients with osteopenia/osteoporosis, hypercalciuria, and recurring renal calcium lithiasis.

Urology, 81(4):731-737.

OBJECTIVE: To analyze the effects of aminobisphosphonates and thiazides on renal lithogenic activity and bone mineral density in patients with recurring renal calcium lithiasis.

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 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.

RESULTS: Age, sex, baseline biochemical markers, and bone density showed no differences between the 2 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.

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.

RevDate: 2016-11-25
CmpDate: 2012-02-17

Okuyama M (2011)

[Epidemiology of urolithiasis].

Clinical calcium, 21(10):1442-1447.

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.

RevDate: 2018-11-13
CmpDate: 2012-05-09

Reilly RF, CL Huang (2011)

The mechanism of hypocalciuria with NaCl cotransporter inhibition.

Nature reviews. Nephrology, 7(11):669-674.

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.

RevDate: 2013-11-21
CmpDate: 2013-02-04

Konstantynowicz J, Porowski T, Zoch-Zwierz W, et al (2012)

A potential pathogenic role of oxalate in autism.

European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 16(5):485-491.

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.

AIM: The objective was to determine oxalate levels in plasma and urine in autistic children in relation to other urinary parameters.

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.

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) μmol/L (p < 0.05)] and 2.5-fold greater urinary oxalate concentrations (p < 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.

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.

RevDate: 2015-11-19
CmpDate: 2012-02-27

Arrabal-Polo MA, Arrabal-Martin M, de Haro-Muñoz T, et al (2012)

Biochemical determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis.

Urology, 79(1):48-54.

OBJECTIVE: To analyze the biochemical alterations in plasma and the urine determinants of severe lithogenic activity in patients with idiopathic calcium nephrolithiasis.

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.

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 β-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).

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, β-crosslaps>0.400 ng/mL, and β-crosslaps/osteocalcin quotient>0.028.

RevDate: 2015-11-19
CmpDate: 2011-12-27

Arrabal-Polo MA, Arrabal-Martin M, de Haro-Munoz T, et al (2011)

Mineral density and bone remodelling markers in patients with calcium lithiasis.

BJU international, 108(11):1903-8; discussion 1908.

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.

OBJECTIVES: • 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. • It is possible that many cases hypercalciuria are related to the increase of bone turnover and the predominance of bone resorption phenomena.

PATIENTS AND METHODS: • 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. • An analysis was made of body mass index; abdominal X-ray and/or urography and renal ultrasonography; osteocalcin and β-crosslaps bone markers; calcium and citrate concentrations in the urine; and femur and spinal column bone densitometry. • The results were analyzed by analysis of variance and Pearson's correlation coefficient.

RESULTS: • Patients with relapsed calcium renal lithiasis present a greater BMD loss than those in the O or A groups. • 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). • A statistically significant negative correlation exists between values of β-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 β-crosslaps was accompanied by a lower value of the T-score and a greater loss of BMD. • A positive relationship is observed between β-crosslaps and osteocalcin (R= 0.611; P < 0.001) and between calciuria and cocient β-crosslaps/osteocalcin (R= 0.303; P= 0.001).

CONCLUSIONS: • A statistically significant relationship is shown between the loss of BMD and relapsed calcium renal lithiasis. • Determination of bone remodelling markers (i.e. osteocalcin and β-crosslaps) facilitates the diagnosis of osteopaenia/osteoporosis in these patients.

RevDate: 2018-11-13
CmpDate: 2012-11-06

Spivacow FR, Negri AL, del Valle EE, et al (2012)

Persistence of hypercalciuria after successful surgical treatment for primary hyperparathyroidism.

International urology and nephrology, 44(3):857-863.

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.

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.

RevDate: 2018-11-13
CmpDate: 2011-09-01

Letavernier E, Traxer O, Daudon M, et al (2011)

Determinants of osteopenia in male renal-stone-disease patients with idiopathic hypercalciuria.

Clinical journal of the American Society of Nephrology : CJASN, 6(5):1149-1154.

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.

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.

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.

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.

RevDate: 2020-03-05
CmpDate: 2011-09-08

Gürgöze MK, MY Sarı (2011)

Results of medical treatment and metabolic risk factors in children with urolithiasis.

Pediatric nephrology (Berlin, Germany), 26(6):933-937.

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.

RevDate: 2013-11-21
CmpDate: 2011-06-22

Swaddiwudhipong W, Mahasakpan P, Limpatanachote P, et al (2011)

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: a population study.

Environmental research, 111(4):579-583.

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.

RevDate: 2010-12-10
CmpDate: 2010-10-29

Valle Díaz de la Guardia F, Arrabal Martín M, Arrabal Polo MA, et al (2010)

Renal lithiasis in patients with primary hyperparathyroidism. Evolution and treatment.

Archivos espanoles de urologia, 63(1):32-40.

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.

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.

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.

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.

RevDate: 2011-05-03
CmpDate: 2011-07-01

Holt K (2010)

Calcium imbalance, resulting disorders and the available prevention and treatment options.

The Journal of practical nursing, 60(4):13-21.

RevDate: 2018-11-13
CmpDate: 2010-09-29

Bibilash BS, Vijay A, YM Fazil Marickar (2010)

Stone composition and metabolic status.

Urological research, 38(3):211-213.

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.

RevDate: 2018-11-13
CmpDate: 2009-10-08

Porowski T, Konstantynowicz J, Zoch-Zwierz W, et al (2009)

Spontaneous urinary calcium oxalate crystallization in hypercalciuric children.

Pediatric nephrology (Berlin, Germany), 24(9):1705-1710.

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.

RevDate: 2020-03-17
CmpDate: 2009-03-19

Escribano J, Balaguer A, Pagone F, et al (2009)

Pharmacological interventions for preventing complications in idiopathic hypercalciuria.

The Cochrane database of systematic reviews.

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.

OBJECTIVES: To assess the benefits and harms of pharmacological interventions for preventing complications and decreasing urological symptoms in patients with idiopathic hypercalciuria.

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.

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.

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).

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.

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.

RevDate: 2018-12-01
CmpDate: 2009-03-04

Corbetta S, Eller-Vainicher C, Frigerio M, et al (2009)

Analysis of the 206M polymorphic variant of the SLC26A6 gene encoding a Cl- oxalate transporter in patients with primary hyperparathyroidism.

European journal of endocrinology, 160(2):283-288.

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.

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.

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.

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.

RevDate: 2019-12-10
CmpDate: 2008-10-29

Kamińska A, Sołtyski J, M Roszkowska-Blaim (2008)

[Usefulness of Pak's test in Stapleton's modification in diagnosis of hypercalciuria in children].

Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 24 Suppl 4:38-40.

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.

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.

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.

RevDate: 2013-11-21
CmpDate: 2009-02-20

Pasch A, Frey FJ, Eisenberger U, et al (2008)

PTH and 1.25 vitamin D response to a low-calcium diet is associated with bone mineral density in renal stone formers.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 23(8):2563-2570.

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.

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.

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.

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.

RevDate: 2018-11-13
CmpDate: 2008-11-14

Porowski T, Zoch-Zwierz W, Konstantynowicz J, et al (2008)

A new approach to the diagnosis of children's urolithiasis based on the Bonn Risk Index.

Pediatric nephrology (Berlin, Germany), 23(7):1123-1128.

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.

RevDate: 2019-12-10
CmpDate: 2008-06-26

Renkema KY, Alexander RT, Bindels RJ, et al (2008)

Calcium and phosphate homeostasis: concerted interplay of new regulators.

Annals of medicine, 40(2):82-91.

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.

RevDate: 2013-11-21
CmpDate: 2008-07-01

Obligado SH, DS Goldfarb (2008)

The association of nephrolithiasis with hypertension and obesity: a review.

American journal of hypertension, 21(3):257-264.

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.

RevDate: 2018-03-30
CmpDate: 2008-02-14

Frassetto LA, Morris RC, Sellmeyer DE, et al (2008)

Adverse effects of sodium chloride on bone in the aging human population resulting from habitual consumption of typical American diets.

The Journal of nutrition, 138(2):419S-422S.

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.

RevDate: 2008-04-10
CmpDate: 2008-05-22

Stejskal D, Karpisek M, Vrtal R, et al (2008)

Urine fetuin-A values in relation to the presence of urolithiasis.

BJU international, 101(9):1151-1154.

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.

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.

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
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.

RevDate: 2019-12-10
CmpDate: 2008-01-23

Dussol B, Verdier JM, Goff JM, et al (2007)

Artificial neural networks for assessing the risk factors for urinary calcium stones according to gender and family history of stone.

Scandinavian journal of urology and nephrology, 41(5):414-418.

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.

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.

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.

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.

RevDate: 2007-08-14
CmpDate: 2007-07-16

Liu CC, Huang CH, Wu WJ, et al (2007)

Association of vitamin D receptor (Fok-I) polymorphism with the clinical presentation of calcium urolithiasis.

BJU international, 99(6):1534-1538.

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.

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.

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.

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.

RevDate: 2018-11-13
CmpDate: 2007-06-18

Bolland MJ, Ames RW, Horne AM, et al (2007)

The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women.

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 18(4):479-486.

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.

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.

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.

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.

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.

RevDate: 2013-11-21
CmpDate: 2006-12-22

Mente A, Honey RJ, McLaughlin JM, et al (2006)

High urinary calcium excretion and genetic susceptibility to hypertension and kidney stone disease.

Journal of the American Society of Nephrology : JASN, 17(9):2567-2575.

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.

RevDate: 2018-11-13
CmpDate: 2007-02-22

Korkes F, Segal AB, Heilberg IP, et al (2006)

Immobilization and hypercalciuria in children.

Pediatric nephrology (Berlin, Germany), 21(8):1157-1160.

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.

RevDate: 2013-11-21
CmpDate: 2006-08-04

Nicoletta JA, MB Lande (2006)

Medical evaluation and treatment of urolithiasis.

Pediatric clinics of North America, 53(3):479-91, vii.

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.

RevDate: 2016-10-19
CmpDate: 2006-11-02

Hoopes RR, Middleton FA, Sen S, et al (2006)

Isolation and confirmation of a calcium excretion quantitative trait locus on chromosome 1 in genetic hypercalciuric stone-forming congenic rats.

Journal of the American Society of Nephrology : JASN, 17(5):1292-1304.

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.

RevDate: 2013-11-21
CmpDate: 2006-05-16

Skodrić-Trifunović V, V Vucinić-Mihailović (2005)

[The role of vitamin D in the formation of granuloma and in calcium metabolism].

Medicinski pregled, 58 Suppl 1:17-20.

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.

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.

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.

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.

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.

CONCLUSION: Examinations of abdominal organ involvement should be a standard procedure in each patient affected with sarcoidosis.

RevDate: 2013-11-21
CmpDate: 2006-06-08

Osther PJ (2006)

Effect of acute acid loading on acid-base and calcium metabolism.

Scandinavian journal of urology and nephrology, 40(1):35-44.

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.

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.

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.

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.

RevDate: 2013-11-21
CmpDate: 2005-12-08

Baggio B, A Budakovic (2005)

Fatty acids and idiopathic calcium nephrolithiasis.

Urologia internationalis, 75(2):97-101.

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.

RevDate: 2005-08-09
CmpDate: 2005-10-06

Sharma OP, V Vucinić (2002)

Sarcoidosis of the thyroid and kidneys and calcium metabolism.

Seminars in respiratory and critical care medicine, 23(6):579-588.

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.

RevDate: 2018-11-13
CmpDate: 2006-01-03

Biyikli NK, Alpay H, T Guran (2005)

Hypercalciuria and recurrent urinary tract infections: incidence and symptoms in children over 5 years of age.

Pediatric nephrology (Berlin, Germany), 20(10):1435-1438.

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.

RevDate: 2013-11-21
CmpDate: 2005-10-25

Damasio B, Massarino F, Durand F, et al (2005)

Prevalence of fasting hypercalciuria associated with increased citraturia in the ambulatory evaluation of nephrolithiasis.

Journal of nephrology, 18(3):262-266.

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.

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.

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.

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.

RevDate: 2020-09-30
CmpDate: 2012-10-30

Rao TV, VK Choudhary (2005)

Effect of pyridoxine (Vitamin-B(6)) supplementation on calciuria and oxaluria levels of some normal healthy persons and urinary stone patients.

Indian journal of clinical biochemistry : IJCB, 20(2):166-169.

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.

RevDate: 2016-11-24
CmpDate: 2005-09-27

Tsuji H, Umekawa T, Kurita T, et al (2005)

Analysis of bone mineral density in urolithiasis patients.

International journal of urology : official journal of the Japanese Urological Association, 12(4):335-339.

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.

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.

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).

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.

RevDate: 2017-01-26
CmpDate: 2006-01-19

Chandhoke PS (2005)

Metabolic abnormalities and the medical management of calcium oxalate nephrolithiasis.

Minerva urologica e nefrologica = The Italian journal of urology and nephrology, 57(1):9-16.

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.

RevDate: 2013-11-21
CmpDate: 2006-03-02

Ceylan K, Topal C, Erkoc R, et al (2005)

Effect of indapamide on urinary calcium excretion in patients with and without urinary stone disease.

The Annals of pharmacotherapy, 39(6):1034-1038.

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.

OBJECTIVE: To determine the hypocalciuric and other effects on certain laboratory parameters of indapamide 1.5 mg in different patient groups.

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.

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.

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.

RevDate: 2019-09-06
CmpDate: 2005-10-26

Yatzidis H (2004)

Gestational urinary hyperthiosulfaturia protects hypercalciuric normal pregnant women from nephrolithiasis.

International urology and nephrology, 36(3):445-449.

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.

RevDate: 2016-11-24
CmpDate: 2005-04-06

Escribano J, Balaguer A, Martin R, et al (2004)

Childhood idiopathic hypercalciuria--clinical significance of renal calyceal microlithiasis and risk of calcium nephrolithiasis.

Scandinavian journal of urology and nephrology, 38(5):422-426.

OBJECTIVE: To evaluate the clinical significance of renal calyceal microlithiasis (RCM) in children with idiopathic hypercalciuria (IHC).

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.

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).

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.

RevDate: 2019-11-09
CmpDate: 2005-04-28

Rebelo MA, Tostes V, Araújo NC, et al (2005)

Screening for CLCN5 mutation in renal calcium stone formers patients.

Anais da Academia Brasileira de Ciencias, 77(1):95-101.

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.

CONCLUSION: CLCN5 gene mutation is not a common cause of kidney stone disease or nephrocalcinosis in a group of Brazilian patients studied.

RevDate: 2013-11-21
CmpDate: 2005-06-28

Moe OW, O Bonny (2005)

Genetic hypercalciuria.

Journal of the American Society of Nephrology : JASN, 16(3):729-745.

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.

RevDate: 2019-11-09
CmpDate: 2005-05-10

Kazantzis G (2004)

Cadmium, osteoporosis and calcium metabolism.

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 17(5):493-498.

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.

RevDate: 2017-01-18
CmpDate: 2006-03-14

Devuyst O, Jouret F, Auzanneau C, et al (2005)

Chloride channels and endocytosis: new insights from Dent's disease and ClC-5 knockout mice.

Nephron. Physiology, 99(3):p69-73.

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.

RevDate: 2013-11-21
CmpDate: 2005-07-25

Devuyst O (2004)

Chloride channels and endocytosis: new insights from Dent's disease and CLC-5 knockout mice.

Bulletin et memoires de l'Academie royale de medecine de Belgique, 159(Pt 2):212-217.

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.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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OK, this book I have not actually read. But it seems super relevant, it is from a reputable publisher, and the table of contents looks genuinely interesting. Given that I have personally had big kidney stones removed twice (once via percutaneous nephrolithotomy, the next time via shockwave lithotripsy) and that (a) I still have some stones in one kidney and (b) I have just been shown to have hypercalciuria, I guess it is time for me to put a book like this on my must-read list. And maybe it is also time to ditch the daily dose of calcium pills... R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

short personal version

Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )