A path analysis to investigate the interaction between serum, urinary and demographic factors influencing urine calcium in kidney stone formers.

BACKGROUND: Hypercalciuria is one of the most important urinary risk factors in kidney stone formers. This study aimed to delineate the interaction of some demographic, serum, and urinary risk factors influencing 24-h urinary (24-U) calcium excretion. METHODS: This study was secondary data analysis, using data from 593 kidney stone patients referred to the Labbafinejad kidney stone prevention clinic from March 2015 to May 2019. The study considered serum, urinary and demographic factors that interact to influence 24-U calcium using path analysis. In addition to the direct impact of predictors on the 24-U calcium, this analysis considered the effects of the predictors on the 24-U calcium transmitted by a mediating variable named indirect effects. RESULTS: The results showed that age indirectly affected on 24-U calcium through 25-hydroxy vitamin D (25(OH)D), serum and 24-U creatinine. As well, weight had an indirect effect through 24-urine metabolites (creatinine, citrate, urea, and sodium). Among serum variables, PTH and creatinine significantly directly affected on 24-U calcium. In comparison, 25(OH)D and phosphorus appeared to influence 24-U calcium indirectly through serum parathormone. Regarding 24-U metabolites, sodium, urea, and citrate had a significant direct effect on 24-U calcium. Moreover, 24-U creatinine has a significant direct and indirect effect on 24-U calcium through citrate and urea as mediator variables. CONCLUSION: Serum 25(OH)D and phosphorus, along with age and weight, indirectly affected urinary calcium through a third variable. Other variables (PTH, serum creatinine, and 24-U sodium, urea, and citrate) showed a direct effect on 24-U calcium excretion.

Dietary management of hypocitraturia in children with urolithiasis: results from a systematic review.

PURPOSE: Hypocitraturia is a low urinary excretion of citrate and a well-known risk factor for kidney stone development in children. This systematic review aimed to evaluate the dietary management of hypocitraturia in children with urolithiasis. METHODS: Literature search was performed on 30th September 2022 using Embase, PubMed, and Cochrane Central Controlled Register of Trials. Studies were included if children with stones and hypocitraturia were managed with diet supplements. RESULTS: Six papers were included. Four studies evaluated the role of oral potassium citrate associated with high fluid intake on stone resolution and recurrence. Two studies assessed the impact of oral potassium citrate on long-term stone recurrence after percutaneous nephrolithotomy and shock wave lithotripsy. All studies demonstrated that the association of potassium citrate and high fluid intake was well tolerated with no side effects and restored normal urine citrate excretion, allowed a reduction in stone size, and, following definitive treatments, was associated with a lower rate of stone regrowth and recurrence compared with controls. These effects were demonstrated across all pediatric ages. CONCLUSIONS: Our review infers that oral potassium citrate and high fluid assumption are safe and effective in restoring urine citrate excretion, treating and preventing stone recurrence with no serious adverse events, and should probably be the first-line treatment of pediatric patients with asymptomatic stones and hypocitraturia.

What treatments reduce kidney stone risk in patients with bowel disease?

We examined how physicians made therapeutic choices to decrease stone risk in patients with bowel disease without colon resection, many of whom have enteric hyperoxaluria (EH), at a single clinic. We analyzed clinic records and 24-h urine collections before and after the first clinic visit, among 100 stone formers with bowel disease. We used multivariate linear regression and t tests to compare effects of fluid intake, alkali supplementation, and oxalate-focused interventions on urine characteristics. Patients advised to increase fluid intake had lower initial urine volumes (L/day; 1.3 ± 0.5 vs. 1.7 ± 0.7) and increased volume more than those not so advised (0.7 ± 0.6 vs. 0.3 ± 0.6 p = 0.03; intervention vs. non-intervention). Calcium oxalate supersaturation (CaOx SS) fell (95% CI -4.3 to -0.8). Alkali supplementation increased urine pH (0.34 ± 0.53 vs. 0.22 ± 0.55, p = 0.26) and urine citrate (mg/d; 83 ± 256 vs. 98 ± 166, p = 0.74). Patients advised to reduce oxalate (mg/day) absorption had higher urine oxalate at baseline (88 ± 44 vs. 50 ± 26) which was unchanged on follow-up (88 (baseline) vs. 91 (follow-up), p = 0.90). Neither alkali (95% CI -1.4 to 2.1) nor oxalate-focused advice (95% CI -1.2 to 2.3) lowered CaOx SS. Physicians chose treatments based on baseline urine characteristics. Advice to increase fluid intake increased urine volume and decreased CaOx SS. Alkali and oxalate interventions were ineffective.

The effects of drinking bicarbonate-rich mineral water in calcium oxalate stone formers: an open label prospective randomized controlled study in an Asian cohort.

PURPOSE: To examine the effects of drinking bicarbonate-rich mineral water in patients with calcium oxalate stones. MATERIALS AND METHODS: This was an open label prospective randomized controlled study comparing the effects of a bicarbonate-rich mineral water versus plain water on urine biochemistry in patients with calcium oxalate stones. The mineral water group were instructed to consume 1.25 L of mineral water per day at meal times, and supplemented by plain water. Their total intake was up to 3 L/day. Control group consumed only plain water up to 3 L/day. 24 h urine analyses were performed at baseline, 1, 4, 8 and 12 weeks after starting protocol. RESULTS: 58 patients were recruited for the study. 51 patients were included in the final analysis. Baseline data were comparable between the two groups. Over the course of 12 weeks, compared to patients drinking plain water, those drinking mineral water had higher overall urinary volume (difference = 644.0 ml/24 h, 95% CI = (206.7, 1081.3)), higher overall urinary magnesium (difference = 1.894 mmol/24 h, 95% CI = (1.006, 2.782)), and pH (difference = 0.477, 95% CI = (0.149, 0.804)). However, there was no difference in urinary oxalate and Tiselius index. Mineral water group had net increase of urinary citrate (at each study point compared to baseline) which was sustained until week 12, whereas plain water group showed no significant change. CONCLUSIONS: Drinking bicarbonate-rich mineral water in calcium oxalate stone formers increased stone inhibitors such as magnesium, citrate and moderate degree of urinary alkalinization compared to patients drinking plain water, but it did not alter Tiselius index or urinary oxalate after 12 weeks.

Beta-thalassaemia major: Prevalence, risk factors and clinical consequences of hypercalciuria.

Regular transfusion and chelation therapy produces increased life expectancy in thalassaemic patients who may develop new complications. Since few data are available regarding hypercalciuria in ß-thalassaemia major (TM), the aim of our study was to evaluate its prevalence, risk factors and clinical consequences. We enrolled 176 adult TM patients followed at the Center of Thalassemia of Ferrara. Hypercalciuria was defined by a calciuria of 4 mg/kg/day or more in a 24-h urine sample. Anamnestic, biochemical and radiological data were collected. Hypercalciuria prevalence was reported in 69.3% of patients (females 52.5%). Hypercalciuric (HC) patients used deferasirox (DFX) more often than normocalciuric (NC) patients (47.5% vs 29.6%; p < 0.05). In HC subjects plasma parathyroid hormone (PTH) (24.1 ± 10.4 vs 30.1 ± 13.2 pg/ml) and phosphate levels (3.6 ± 0.5 vs 3.8 ± 0.7 mg/dl) were lower, whereas serum calcium (9.6 ± 0.4 vs 9.4 ± 0.4 mg/dl) and urinary 24-h phosphaturia (0.9 ± 0.4 vs 0.6 ± 0.3 g/day) were higher as compared to NC patients (p < 0.05 for all comparisons). Supplementation with oral calcium and cholecalciferol was similar between the groups. A higher rate of kidney stones was present in HC (14.8%) versus NC patients (3.7%) (p < 0.05). Hypercalciuria is a frequent complication in adequately treated adult TM patients. Hypercalciuria prevalence is increased in DFX users whereas haemoglobin level or calcium supplements play no role. A significant proportion of HC patients developed kidney stones.

Effect of Black Tea Consumption on Urinary Risk Factors for Kidney Stone Formation.

Copious fluid intake is the most essential nutritional measure in the treatment of urolithiasis, and is suggested to be a protective factor in the primary prevention of urinary stone formation. Although the intake of black tea contributes to daily fluid intake, the high oxalate content could outweigh the beneficial effect of urine dilution. The present study investigated the effect of black tea consumption on urinary risk factors for kidney stone formation. Ten healthy men received a standardized diet for a period of ten days. Subjects consumed 1.5 L/day of fruit tea (0 mg/day oxalate) during the 5-day control phase, which was replaced by 1.5 L/day of black tea (86 mg/day oxalate) during the 5-day test phase. Fractional and 24-h urines were obtained. The intake of black tea did not significantly alter 24-h urinary oxalate excretion. Urinary citrate, an important inhibitor of calcium stone formation, increased significantly, while the relative supersaturation of calcium oxalate, uric acid, and struvite remained unchanged. No significantly increased risk for kidney stone formation could be derived from the ingestion of black tea in normal subjects. Further research is needed to evaluate the impact of black tea consumption in kidney stone patients with intestinal hyperabsorption of oxalate.

Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats.

Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = - 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.

The Efficacy of Polyunsaturated Fatty Acids as Protectors against Calcium Oxalate Renal Stone Formation: A Review.

In the pathogenesis of hypercalciuria and hyperoxaluria, n-6 polyunsaturated fatty acids (PUFAs) have been implicated by virtue of their metabolic links with arachidonic acid (AA) and prostaglandin PGE2. Studies have also shown that n-3 PUFAs, particularly those in fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-can serve as competitive substrates for AA in the n-6 series and can be incorporated into cell membrane phospholipids in the latter's place, thereby reducing urinary excretions of calcium and oxalate. The present review interrogates several different types of study which address the question of the potential roles played by dietary PUFAs in modulating stone formation. Included among these are human trials that have investigated the effects of dietary PUFA interventions. We identified 16 such trials. Besides fish oil (EPA+DHA), other supplements such as evening primrose oil containing n-6 FAs linoleic acid (LA) and γ-linolenic acid (GLA) were tested. Urinary excretion of calcium or oxalate or both decreased in most trials. However, these decreases were most prominent in the fish oil trials. We recommend the administration of fish oil containing EPA and DHA in the management of calcium oxalate urolithiasis.

Exploring the Potential Relationship Between Phytate Ingestion, Urinary Phytate Excretion, and Renal Stone Risk in a Unique Human Model: No Hard Evidence in Support of Phytate as a Stone Inhibitor.

OBJECTIVE: Dietary phytate (IP6) enjoys a reputation as an inhibitor of calcium renal stone formation, although there are very few human studies to support this notion. In South Africa, urolithiasis occurs in the white (W) but is rare in the black (B) population. We undertook this unique human model to further investigate the IP6 theory. METHODS: Healthy W and B males completed baseline food-frequency recall questionnaires. Dietary intake of IP6 was restricted for 18 days. An IP6 dietary supplement was ingested on days 15-18. Twenty-four-hour urinary phytate and other urinary components were determined. Relative supersaturations of calcium salts were calculated. The urinary metastable limit (MSL) of calcium oxalate (CaOx) and its crystallisation kinetics were determined experimentally. RESULTS: Habitual dietary intake of IP6 and its urinary excretion were significantly higher in B than in W (1650 ± 202 vs. 640 ± 134 mg/d, P = .0002 and 1.13 ± 0.12 vs. 0.75 ± 0.13 µM, P <.05, respectively). In B, urinary phytate decreased significantly after 15 days of IP6 restriction, but in W, its excretion remained constant. After supplementation, urinary IP6 increased significantly in both groups reaching levels commensurate with the baseline value in B. No significant differences occurred in B in any of the routine urinary risk factors throughout the trial. However, in W, urinary citrate excretion increased on day 18 relative to day 0. There were no significant intragroup or intergroup changes in relative supersaturation, metastable limit, or crystallization kinetics. CONCLUSIONS: Despite notable differences in the renal handling of ingested IP6, there were no changes in any of the well-established urinary risk factors for calcium renal stone formation in either of our uniquely different test groups. We conclude that, in the absence of hard evidence, claims that IP6 is a stone inhibitor remain unproven.

Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy.

OBJECTIVE: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. MATERIALS AND METHODS: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and pro-biotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats re-ceived Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. FINDINGS: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) redu-ced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. CONCLUSION: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalatedegrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy

ABSTRACT Objective: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. Materials and Methods: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and probiotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats received Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. Findings: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) reduced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. Conclusion: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalate degrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

Hydroxycitrate: a potential new therapy for calcium urolithiasis.

Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.

Daily Green Tea Infusions in Hypercalciuric Renal Stone Patients: No Evidence for Increased Stone Risk Factors or Oxalate-Dependent Stones.

Green tea is widely used as a ''healthy'' beverage due to its high level of antioxidant polyphenol compounds. However tea is also known to contain significant amount of oxalate. The objective was to determine, in a cross-sectional observational study among a population of 273 hypercalciuric stone-formers referred to our center for metabolic evaluation, whether daily green tea drinkers (n = 41) experienced increased stone risk factors (especially for oxalate) compared to non-drinkers. Stone risk factors and stone composition were analyzed according to green tea status and sex. In 24-h urine collection, the comparison between green tea drinkers and non-drinkers showed no difference for stone risk factors such as urine oxalate, calcium, urate, citrate, and pH. In females, the prevalence of calcium oxalate dihydrate (COD) and calcium phosphate stones, assessed by infrared analysis (IRS) was similar between green tea drinkers and non-drinkers, whereas prevalence of calcium oxalate monohydrate (COM) stones was strikingly decreased in green tea drinkers (0% vs. 42%, p = 0.04), with data in accordance with a decreased oxalate supersaturation index. In males, stone composition and supersaturation indexes were similar between the two groups. Our data show no evidence for increased stone risk factors or oxalate-dependent stones in daily green tea drinkers.

Comparison of metabolic changes for stone risks in 24-hour urine between non- and postmenopausal women.

BACKGROUND: To explore the differences of 24-hour urine compositions associated with urolithiasis between non- and postmenopausal females. METHODS: The 24-hour urine samples of female participants were collected from May 2013 to July 2014 along with national cross-sectional study of urolithiasis among adults aged ≥18 years in China. The exclusion criteria for the participants were: serum creatinine > 133µmol/L, with urinary tract infection, gout, hyperthyroidism, malignancy, had a history of cancer, kidney stones, enterectomy, had taken thiazide diuretics, allopurinol, vitamin supplement, potassium citrate or calcium supplements during the past two weeks. The compositions associated with urinary stone in 24-hour urine were measured and compared between non-and postmenopausal women. RESULTS: A total of 603 24-hour urine samples of female participants were analyzed. 354 women with a mean age of 52.5± 14.03 (range 19-84) years met the criteria, including 160 non-menopausal women and 194 postmenopausal women. Compared to the non-menopausal women, postmenopausal women had a lower secretion of citrate (p = 0.043), magnesium (p = 0.001) and creatinine (p = 0.001) in 24h urine. Multivariate linear regression analysis showed that the menopause status was associated with the changes in magnesium (p = 0.003) and creatinine (p = 0.002) secretion, whereas not with the changes in citrate (p = 0.402) secretion. CONCLUSIONS: Postmenopausal women have a significant lower secretion of magnesium in their 24-hour urine than non-menopausal ones. We suppose that might be associated with increased risk of urinary stone formation among postmenopausal women.

Amelioration of hyperoxaluria-induced kidney dysfunction by chemical chaperone 4-phenylbutyric acid.

Hyperoxaluria is characterized by an increased excretion of urinary oxalate which is caused by inherited disorders or high oxalate intake leading to renal stone ailment. Until date, reactive oxygen species and inflammation has been convicted for the progression of kidney stones for which antioxidant therapy has been employed. However, recent studies have linked the association of endoplasmic reticulum stress and oxidative imbalance in the progression of renal diseases. Considering oxidative stress being at forefront in causing hyperoxaluric consequences, current study was designed to correlate the impact of hyperoxaluria and regulation of oxidative imbalance via inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid (4-PBA). Male wistar rats were subdivided into three groups, i.e., normal control (C), hyperoxaluric rats given ethylene glycol (EG), and hyperoxaluric rats treated with 4-PBA (EG + PBA). After 28 days of treatment, assessment of antioxidant defence system, inflammation, ER stress, and subsequent unfolded protein response was studied in renal tissue. It was found that the hyperoxaluric insult led to a marked damage to the renal tissue resulting in compromised antioxidant levels, upregulation of ER stress markers along with a steep surge in the extent of inflammation. However, 4-PBA treatment significantly curtailed the deleterious effects of hyperoxaluria by lowering down the level of stress markers as well as normalizing the antioxidant defence enzymes. Therefore, chemical chaperones can be deemed as a new class of drugs for the treatment of hyperoxaluric induced renal damage.

Initial collection of an inadequate 24-hour urine sample in children does not predict subsequent inadequate collections.

INTRODUCTION: Approximately half of adult stone formers submit specimens that are either under or over collections as determined by 24-h creatinine/kg. Previously identified predictors of inadequate collection in adults include female sex, older age, higher body mass index (BMI), vitamin D supplementation, and weekday collection. OBJECTIVE: The objective of this study is to determine risk factors for inadequate 24-h urinary specimen collection in the pediatric population. STUDY DESIGN: A retrospective analysis of all children (<18 years of age) with renal and/or ureteral calculi evaluated at the study tertiary care pediatric center from 2005 to 2015 was performed. Those who had at least one 24-h urinary metabolic profile after a clinical visit for kidney and/or ureteral stones were included; children with bladder stones were excluded. Adequate collections had a urine creatinine of 10-15 mg/kg/24 h. A bivariate analysis of potential factors associated with inadequate collection of the initial urinary metabolic profile, including child demographics, parental socio-economic factors, history of stone surgery, and weekday vs. weekend urine collection, was performed. A mixed-effects logistic regression, controlling for correlation of specimens from the same patient, was also performed to determine whether an initial inadequate collection predicted a subsequent inadequate collection. RESULTS: Of 367 patients, 80 had an adequate collection (21.9%): median age, 13 years (interquartile range, 8-16); 61.1% female; 93.5% white; 19.5% obese; and 13.0% overweight. No parental or child factors were associated with inadequate collection (Summary Table). Of inadequate collections, more than 80% were over collections. In the 175 patients with more than one 24-h urinary specimen collection, the effect of an initial inadequate collection on subsequent inadequate collections was not significant after controlling for the correlation of samples from the same patient (p = 0.8). DISCUSSION: Any parental or child factors associated with the collection of inadequate 24-h urine specimens in children were not found. An initial inadequate collection does not predict subsequent inadequate collections. It was surprising that >80% of the inadequate collections were over collections rather than under collections. Possible explanations are that children collected urine samples for longer than the 24-h period or that stone-forming children produce more creatinine per 24-h period than healthy children due to hyperfiltration. CONCLUSION: Inadequate collections are very common, and the risk factors for them are unclear. A repeat collection would be suggested if the first is inadequate. Further studies must be planned to explore barriers to accurate specimen collection using qualitative research methodology.

Seasonal variations in urinary calcium, volume, and vitamin D in kidney stone formers

ABSTRACT Objectives: To investigate the seasonal variations in urinary calcium, serum vitamin D, and urinary volume in patients with a history of nephrolithiasis. Materials and Methods: Patients included were those who completed a 24-hour urine metabolic evaluation on two occasions; one in summer (June-Aug) and one in winter (Nov-Jan), and who had not started any medications or been instructed on dietary modifications in the interval between the two tests that may have impacted the results. Patients were excluded if they were on thiazide diuretics or were taking calcium and / or Vitamin D supplementation. Welch's t-test was used to compare the difference in average summer and winter values. Unpaired Student t-test was used to compare baseline parameters (age, BMI), and Paired Student t-test was used to compare average seasonal measurements in men vs. women. Results: 136 patients were identified who were not taking calcium or vitamin D supplements or thiazide diuretics, and who were not instructed on dietary modifications in the interval between the two measured parameters. No significant differences were observed when comparing male to female baseline parameters of age or BMI (Table-1). Average 24-hour urine calcium was higher (226.60) in the winter than in summer (194.18) and was significant in males (p = 0.014) and females (p < 0.001). No significant seasonal difference was seen in 24-hour urine volume or serum vitamin D levels. Conclusions: Urinary calcium is higher in winter months compared to summer months. As such, tailoring medical preventative strategies to the time of year may be helpful.

Safety of calcium and vitamin D supplements, a randomized controlled trial.

OBJECTIVE: It is anticipated that an intake of vitamin D found acceptable by Endocrine Society Guidelines (10 000 IU/day) with co-administered calcium supplements may result in frequent hypercalciuria and hypercalcaemia. This combination may be associated with kidney stones. The objective of this study was to compare the episodes of hypercalciuria and hypercalcaemia from calcium supplements co-administered with 10 000 IU or 600 IU vitamin D daily. This design allows a comparison of the Institute of Medicine recommendation for the RDA of vitamin D along with the upper limit of calcium intake with the high intake of vitamin D suggested by the Endocrine Society. CONTEXT: Harms of currently recommended high intake of vitamin D have not been studied. DESIGN: The design was a randomized controlled trial with 2 groups with evaluation every 3 months for one year: (a) CaCO3 1200 mg/day with 10 000 IU vitamin D3 /day or (b) CaCO3 1200 mg/day with 600 IU vitamin D3 /day. PATIENTS: This study was conducted in an ambulatory research centre in healthy, white postmenopausal women. MEASUREMENTS: Serum and 24-hour urine calcium were measured. RESULTS: Hypercalcaemia and hypercalciuria occurred in both groups. At the final visit, 19/48 in the high dose D group had hypercalciuria. The odds of developing hypercalciuria were 3.6 [OR = 3.6(1.39, 9.3)] times higher in the high dose D group. The odds of developing hypercalcaemia did not differ between groups. CONCLUSIONS: The safe upper level of vitamin D recommended by the Endocrine Society when accompanied by calcium supplements results in frequent hypercalciuria. The risk of kidney stones at these levels should be investigated.

Seasonal variations in urinary calcium, volume, and vitamin d in kidney stone formers.

OBJECTIVES: To investigate the seasonal variations in urinary calcium, serum vitamin D, and urinary volume in patients with a history of nephrolithiasis. MATERIALS AND METHODS: Patients included were those who completed a 24-hour urine metabolic evaluation on two occasions; one in summer (June-Aug) and one in winter (Nov-Jan), and who had not started any medications or been instructed on dietary modifications in the interval between the two tests that may have impacted the results. Patients were excluded if they were on thiazide diuretics or were taking calcium and / or Vitamin D supplementation. Welch's t-test was used to compare the difference in average summer and winter values. Unpaired Student t-test was used to compare baseline parameters (age, BMI), and Paired Student t-test was used to compare average seasonal measurements in men vs. women. RESULTS: 136 patients were identified who were not taking calcium or vitamin D supplements or thiazide diuretics, and who were not instructed on dietary modifications in the interval between the two measured parameters. No significant differences were observed when comparing male to female baseline parameters of age or BMI (Table-1). Average 24-hour urine calcium was higher (226.60) in the winter than in summer (194.18) and was significant in males (p = 0.014) and females (p < 0.001). No significant seasonal difference was seen in 24-hour urine volume or serum vitamin D levels. CONCLUSIONS: Urinary calcium is higher in winter months compared to summer months. As such, tailoring medical preventative strategies to the time of year may be helpful.

[A young girl with recurrent calculosis and hypercalcemia].

Mutations of the CYP24A1 gene are associated with alterations in the activity of the enzyme 25-OH-D-24-hydroxylase, resulting in dysfunction of the metabolism of vitamin D. This enzymatic deficiency may cause hypercalcemia, low parathyroid hormone levels, hypercalciuria, nephrolithiasis and nephrocalcinosis. The clinical case of a young woman with recurrent renal lithiasis, hypercalcemia and hypercalciuria is described. These features are linked to deficiency of the enzyme 25-OH-D-24-hydroxylase, therefore to a biallelic mutation of the CYP24A1 gene.