Calcium Oxalate Supersaturation Research Articles

Predictive Factors for Achieving the Recommended AUA Daily Urine Production in Patients With Nephrolithiasis.

ObjectiveTo identify factors that predict kidney stone patient's ability to produce 2.5 L urine volume per day on metabolic evaluation.Patients and MethodsIn a retrospective chart review, the first analysis evaluated initial 24-hour urine collections with respect to those who achieved or did not achieve a urine volume of 2.5 L/day. The second analysis evaluated those who achieved or did not achieve a daily urine volume of 2.5 L on their subsequent collection. Several variables were assessed.ResultsPatients’ initial collections (n=1100) that achieved 2.5 L/day (n=274) were of younger age and had a higher body mass index, increased urine sodium, phosphorus, calcium levels, increased protein catabolic rate, and decreased supersaturation of calcium oxalate. In the second analysis (n=273), decreased supersaturation of calcium oxalate, increased urine urea nitrogen level, and increased protein catabolic rate were observed in subsequent collections with a urine volume of 2.5 L/day or more. Patients with a diagnosis of hyponatremia were less likely to achieve 2.5 L/day urine volume. Collection date, other comorbidities, and diuretic use were not associated with achieving 2.5 L/day urine volume. Patients’ mean creatinine per kilogram for all study cohorts were within the range of adequate collection.ConclusionPredictive factors for a urine volume of 2.5 L/day or more include increased fluid intake, higher salt and animal protein diet, elevated body mass index, and male sex. Patients with these factors may require interventions other than hydration recommendations to optimize their prevention of future kidney.

MP08-05 IMPACT OF DEMOGRAPHIC FACTORS AND SYSTEMIC DISEASE ON URINARY STONE RISK PARAMETERS AMONGST STONE FORMERS

This article examines via multivariate analysis the associations between demographic factors and systemic diseases on stone risk parameters in a stone-forming population. A retrospective chart review of adult stone formers who completed 24-hour urine collections from April 2004 through August 2015 was performed. Data was collected on age, sex, race, body mass index (BMI), and diagnoses of diabetes and hypertension. CT imaging and renal/abdominal ultrasonography (within ± 66 mo) were reviewed for diagnosis of fatty liver disease. Statistical analysis included Pearson and Spearman correlation analysis, and linear and logistic regression analyses, both univariate and multivariate. Five hundred eighty-nine patients were included. Numerous urinary parameters were significant in association with demographic factors or systemic diseases in a multivariate analysis. Older age was associated with decreased calcium (Ca) excretion (P = 0.0214), supersaturation of calcium oxalate (SSCaOx; P = 0.0262), supersaturation of calcium phosphate (SSCaP; P < 0.0001), and urinary pH (P = 0.0201). Men excreted more Ca (P = 0.0015) and oxalate (Ox; P = 0.0010), had lower urine pH (P = 0.0269), and higher supersaturation of uric acid (SSUA; P < 0.0001) than women. Blacks had lower urine volume (P = 0.0023), less Ca excretion (P = 0.0142), less Ox excretion (P = 0.0074), and higher SSUA (P = 0.0049). Diabetes was associated with more Ox excretion (P < 0.0001), lower SSCaP (P = 0.0068), and lower urinary pH (P = 0.0153). There were positive correlations between BMI and Ca excretion (P = 0.0386), BMI and Ox excretion (P = 0.0177), and BMI and SSUA (P = 0.0045). These results demonstrate that demographic factors and systemic disease are independently associated with numerous risk factors for kidney stones. The mechanisms responsible for these associations and disparities (racial differences) need to be further elucidated.

PD12-11 24-HOUR URINE CALCIUM OXALATE SUPERSATURATION RISK CORRELATES WITH CT VOLUMETRIC CALCIUM OXALATE STONE GROWTH

INTRODUCTION AND OBJECTIVES:In vitro studies have shown that calcium oxalate supersaturation (CaOX SS) principally drives CaOX stone formation and growth. As this has not been previously validated ...

The Effect of Lemonade and Diet Lemonade Upon Urinary Parameters Affecting Calcium Urinary Stone Formation.

To determine the effects of regular and diet lemonade upon urinary parameters affecting kidney stone formation. In this prospective blinded crossover study, 12 healthy participants consumed either 2 L of regular or diet lemonade daily while on a standardized low sodium moderate calcium diet. Twenty four-hour urine collections were obtained at baseline on the controlled diet only and on days 4 and 5 of each treatment phase. There was a 1-week washout period between regular and diet lemonade treatments. Primary outcomes were urine citrate, pH, and volume determined by 24-hour urine collections. Secondary outcomes included the supersaturation of calcium oxalate, calcium phosphate, and uric acid. Urine volume was significantly higher with both regular and diet lemonade consumption compared with baseline values. Urinary citrate significantly increased from baseline with diet lemonade only. Urine pH was unchanged with both beverages. The supersaturation of calcium oxalate significantly decreased with diet lemonade only, whereas supersaturation of calcium phosphate decreased with both beverages. Daily consumption of 2 L of regular and diet lemonade resulted in an intake of 168.4 and 170.2 mEq of citrate but a total alkali intake of 12.2 and 16.0 mEq, respectively. Compared with diet lemonade, regular lemonade provided subjects with 805 additional calories and 225 g of sugar per day. Diet lemonade may provide a low-calorie sugar-free cost-effective option for decreasing the risk of recurrent calcium nephrolithiasis through a significant increase in urine volume, increase in urinary citrate, and reduction in supersaturation of calcium oxalate and calcium phosphate.

Targeting kidney inflammation as a new therapy for primary hyperoxaluria?

The primary hyperoxalurias (PHs) are inborn errors of glyoxylate metabolism characterized by endogenous oxalate overproduction in the liver, and thus elevated urinary oxalate excretion. The urinary calcium-oxalate (CaOx) supersaturation and the continuous renal accumulation of insoluble CaOx crystals yield a progressive decline in renal function that often ends with renal failure. In PH Type 1 (AGXT mutated), the most frequent and severe condition, patients typically progress to end-stage renal disease (ESRD); in PH Type 2 (GRHPR mutated), 20% of patients develop ESRD, while only one patient with PH Type 3 (HOGA1 mutated) has been reported with ESRD so far. Patients with ESRD undergo frequent maintenance (haemo)dialysis treatment, and finally must receive a combined liver-kidney transplantation as the only curative treatment option available in PH Type 1. In experimental models using oxalate-enriched chow, CaOx crystals were bound to renal tubular cells, promoting a pro-inflammatory environment that led to fibrogenesis in the renal parenchyma by activation of a NACHT, LRR and PYD domains-containing protein 3 (NALP3)-dependent inflammasome in renal dendritic cells and macrophages. Chronic fibrogenesis progressively impaired renal function. Targeting the inflammatory response has recently been suggested as a therapeutic strategy to treat not only oxalate-induced crystalline nephropathies, but also those characterized by accumulation of cystine and urate in other organs. Herein, we summarize the pathogenesis of PH, revising the current knowledge of the CaOx-mediated inflammatory response in animal models of endogenous oxalate overproduction. Furthermore, we highlight the possibility of modifying the NLRP3-dependent inflammasome as a new and complementary therapeutic strategy to treat this severe and devastating kidney disease.

Short-Term Changes in Urinary Relative Supersaturation Predict Recurrence of Kidney Stones: A Tool to Guide Preventive Measures in Urolithiasis

Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment. We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup. During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence. In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive.

Review of post bariatric surgery effects on common genitourinary physiology.

ABSTRACT Background: Obesity is a worldwide challenging health problem. Weight loss through medical management of obesity has not always been successful, thus, giving rise to the need for surgical intervention. Bariatric surgery has been shown to be helpful for morbidly obese patients. However, studies have also shown the effect of surgery on stone formation, fertility and erectile function. This review summarizes the main findings of several studies that analyze stone formation and fertility in men as well as erectile function post bariatric surgery. The underlying pathophysiologic alterations post bariatric surgery include increased absorption of oxalate leading to hyperoxaluria, hypocitraturia and increased urinary calcium oxalate supersaturation. Contradicting data exist on the effect of bariatric surgery on fertility and erectile function. Further studies are needed to analyze the mechanisms.

Relative Supersaturation of 24-Hour Urine and Likelihood of Kidney Stones

The relative supersaturation of calcium oxalate, calcium phosphate and uric acid is used clinically in kidney stone prevention. The magnitude of the association between relative supersaturation and stone risk requires further quantification. We performed a cross-sectional study using 24-hour urine collections from the NHS (Nurses' Health Study) I and II, and HPFS (Health Professionals Follow-up Study) cohorts to quantify the association between the relative supersaturation of calcium oxalate, calcium phosphate and uric acid, and the likelihood of stone formation. The OR of being a stone former was 5.85 (95% CI 3.40-10.04) in NHS I, 6.38 (95% CI 3.72-11.0) in NHS II and 6.95 (95% CI 3.56-13.6) in HPFS for the highest category of calcium oxalate relative supersaturation compared with less than 1.0. The OR of being a stone former was 1.86 (95% CI 0.94-3.71) in NHS I, 4.37 (95% CI 2.68-7.10) in NHS II and 3.59 (95% CI 2.04-6.31) in HPFS for the highest category of calcium phosphate relative supersaturation compared with less than 1.0. For uric acid relative supersaturation the OR of being a stone former was 4.30 (95% CI 2.34-7.90) in NHS I and 2.74 (95% CI 1.71-4.40) in NHS II for the highest relative supersaturation category compared with less than 1.0. In HPFS the uric acid relative supersaturation was not significantly associated with the likelihood of stone formation. The likelihood of being a stone former increases with higher relative supersaturation of calcium oxalate and calcium phosphate in men and women, and with higher relative supersaturation of uric acid in women.

Hyperoxaluria in a Model of Mini-Gastric Bypass Surgery in Rats.

Bariatric surgery is associated with hyperoxaluria hence predisposing to nephrolithiasis. The present study aimed to investigate the underlying mechanisms contributing to increased urinary oxalate in a mini-gastric bypass (MGB) surgery model in rats under different dietary conditions. The expression of intestinal oxalate transporters was also evaluated. Male rats underwent MGB (n=21) or Sham procedure (n=21) and after recovery were fed a standard or high-fat diet with or without oxalate for 8weeks. Stool and urine were collected before surgery (baseline) and at the end of protocol (final), when intestinal fragments were harvested for expression of Slc26a3 and Slc26a6 oxalate transporters. MGB groups fed with fat, irrespective of oxalate supplementation, presented steatorrhea. In MGB animals fed with fat and oxalate (Fat+Ox), final values of urinary oxalate and calcium oxalate supersaturation risk were markedly and significantly increased versus baseline or Sham animals under the same diet, as well as MGB groups under other diets. Slc26a3 was decreased in biliopancreatic limbs of MGB rats, probably reflecting a physiological adaptation to the restriction of food passage. Slc26a6 was not altered in any harvested intestinal fragment. A high-fat and oxalate diet induced hyperoxaluria and elevation in calcium oxalate supersaturation risk in a MGB rat model. The presence of fat malabsorption and increased dietary oxalate absorption, but not modifications of Slc26a3 and Slc26a6 oxalate transporters, accounted for these findings, suggesting that bariatric patients may benefit from a low-fat and low-oxalate diet.

Etiopathogenesis of Nephrolithiasis in Ulcerative Colitis Patients with the Ileal Pouch Anal Anastomosis.

Our previous study showed that nephrolithiasis is a common complication in ulcerative colitis patients after ileal pouch anal anastomosis (IPAA). However, the pathogenesis of nephrolithiasis in IPAA patients has not been studied. The aim of this study was to compare urine and serum metabolic compositions in IPAA patients with nephrolithiasis and controls with IPAA and no nephrolithiasis. Using cross-sectional study design, serum and 24-hour urine metabolic compositions were compared between IPAA patients with nephrolithiasis (the study group) and those without (the control group). Urinary supersaturation of calcium oxalate, calcium phosphate, and uric acid was calculated. A total of 40 patients were enrolled in the study. There were no significant differences in serum electrolytes, vitamin D, parathyroid hormone, and kidney function tests between the study (n = 20) and control groups (n = 20). Patients in the study group were found to have a significantly higher 24-hour urine supersaturation of calcium oxalate (8.8 versus 5.0, P = 0.037) and calcium phosphate (0.61 versus 0.27, P = 0.028) as compared with controls. Nineteen (95%) patients in the study group were symptomatic due to nephrolithiasis with several requiring procedural intervention for treatment, including ureteroscopy in 3 (15%) patients, lithotripsy in 5 (25%) patients, and percutaneous surgery in 1 (5%) patient. Ulcerative colitis-IPAA patients are at risk for the development of calcium oxalate and calcium phosphate stones. Nephrolithiasis is symptomatic in a majority of the patients and frequently requires procedural intervention for treatment.

24 Hour urine metabolic differences between solitary and multiple stone formers: Results of the Collaboration on Urolithiasis in Pediatrics (CUP) working group

Specific factors associated with the risk of developing pediatric urinary stone disease remain unclear, especially those that may be associated with recurrent stone disease. We compared the results of 24-hurine collections in children with a solitary stone episode to those with multiple stone episodes to determine if there is a difference that may be associated with multiple stone formation in children. A multi-institutional retrospective analysis was completed to assess 24-hurinary metabolic profiles in children with urolithiasis aged 2-18 years old. Differences in mean urine collections between the two groups were assessed using chi-square tests to test the associations among gender, stone type, and multiple stone status, as well as multivariate analyses using general linear models. We analyzed 142 solitary stone patients and 136 multiplestone patients from four centers were included. Multiple stone patients were older than solitary stone patients (mean 13.4±3.6 years vs.12±3.9 years, p=0.002). Females were more likely to have multiple stones (58% vs. 39%, p=0.002). BMI was not associated with multiple stones (p=0.8467). Multiple stone formers had lower urine volumes, although this did not reach statistical significance when compared with solitary stone formation (20.4mL/kg/day±11.5 vs. 22.9±13.0, p=0.0880). Higher values for super-saturation of calcium oxalate were associated with multiple stone disease in univariate (p=0.0485) and multivariate analysis (p=0.0469) (Figure). Centers located in the Southeast of the United States saw a higher proportion of children with multiple stones (Tennessee 62.7%, Virginia 44.4%, Oregon 31.6%, Michigan 27.3%, p<0.0001). In a large multi-institutional retrospective analysis we found that multiple stone disease was associated with higher super-saturations of calcium oxalate. Many urinary parameters changed with patient age, highlighting that the values should be interpreted with respect to patient age. The inability to comment on follow-up because of the nature of our dataset is a limitation of this study. Multiple stone disease in children is associated with higher super-saturation calcium oxalate, while lower urinary volume may also be associated with multiple stones; however, further study is required. Early metabolic evaluation may help risk stratify children likely to form multiple stones.

MP12-07 URINE KIDNEY INJURY MARKERS DO NOT INCREASE FOLLOWING GASTRIC BYPASS: A MULTI-CENTER CROSS-SECTIONAL STUDY.

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I1 Apr 2017MP12-07 URINE KIDNEY INJURY MARKERS DO NOT INCREASE FOLLOWING GASTRIC BYPASS: A MULTI-CENTER CROSS-SECTIONAL STUDY. Bryan Hinck, Ricardo Miyaoka, James Lingeman, Dean Assimos, Brian Matlaga, Rocky Pramanik, John Asplin, Benjamin Cohen, and Manoj Monga Bryan HinckBryan Hinck More articles by this author , Ricardo MiyaokaRicardo Miyaoka More articles by this author , James LingemanJames Lingeman More articles by this author , Dean AssimosDean Assimos More articles by this author , Brian MatlagaBrian Matlaga More articles by this author , Rocky PramanikRocky Pramanik More articles by this author , John AsplinJohn Asplin More articles by this author , Benjamin CohenBenjamin Cohen More articles by this author , and Manoj MongaManoj Monga More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.429AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gastric bypass surgery for obesity is known to be associated with post-operative hyperoxaluria, which can lead to urolithiasis and kidney damage. The objective of this study was to determine if markers of kidney injury correlated with urinary oxalate excretion. If so, such biomarkers might be early predictors of oxalate nephropathy. METHODS Patients were recruited from 4 large academic centers > 6 months following completion of gastric bypass surgery. Patients provided a spot urine sample for analysis of three markers of kidney injury: 8-iso-Prostaglandin F2α, N-acetyl-β-D-Glucosaminidase, and Neutrophil gelatinase-associated lipocalin. Patients also provided 24 hour urine samples for stone risk analysis. RESULTS 46 study patients provided samples and the average age was 48.4 + 11.3. There were 40 women and 6 men. There was no difference in the level of any of the three inflammatory markers between the study group and the reference range generated from healthy non-hyperoxaluric subjects. Neither oxalate excretion nor supersaturation of calcium oxalate correlated with any of the injury markers There was no difference noted between those with hyperoxaluria (N=17) and those with normoxaluria (N=29) with respect to any of the injury markers (Table 1). CONCLUSIONS Though hyperoxaluria was common after bypass surgery, markers of kidney injury were not elevated after surgery. No correlation was found between urine oxalate excretion and any of the injury markers. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e147 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Bryan Hinck More articles by this author Ricardo Miyaoka More articles by this author James Lingeman More articles by this author Dean Assimos More articles by this author Brian Matlaga More articles by this author Rocky Pramanik More articles by this author John Asplin More articles by this author Benjamin Cohen More articles by this author Manoj Monga More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Stress-stones-stress-recurrent stones: a self-propagating cycle? Difficulties in solving this dichotomy.

Numerous studies have reported an association between stress and urolithiasis. Although urinary risk factors have been measured in several of these, compelling evidence of a causal relationship has not been established. A shortcoming is that alterations in single urinary parameters rather than ratios and quotients, which provide a more synergistic risk evaluation, have been measured. Recently, we speculated about a possible association between chronic stress and stone recurrence. This presents an intriguing dichotomy of whether stress causes stones or vice versa, or whether they are linked in a self-propagating stress-stones-stress-recurrence cycle. We investigated the latter hypothesis in a retrospective case-control designed study in which we calculated urinary ratios and quotients which are regarded as diagnostic indicators of stone risk. These included Ca/Cr, Ox/Cr, Mg/Cr, Cit/Cr, urate/Cr and citrate-magnesium-calcium ratios, activity product quotient for calcium oxalate (CaOx) and relative supersaturation of CaOx, brushite and uric acid. Overnight urinary data from 128 participants comprising 31 first time (FS), 33 recurrent (RS) CaOx stone formers and 64 controls were used. All subjects had been previously assessed for chronic stress dimensions, as well as for stress caused by their stone episodes per se. Conditional and unconditional logistic regression (with a Bonferroni correction for multiple tests) and simple linear regression were used to analyse various components of the data. Although RS had more stressful life events, with greater intensity of perception than FS, there were no significant differences between the groups regarding any of the urinary risk factors. No significant association between stressful life events and any of the urinary ratios or quotients was observed. A direct causal link between stress and stone recurrence was not indicated. We believe that future studies should shift their focus from traditional urinary risk factors to other stone-forming mechanisms. However, we recognize that there is an inherent problem in attempting to solve the stress-stones dichotomy as it would be impossible to disentangle alterations in risk factors which arise from lifestyle stress and those arising from stone episodes themselves.

Vitamin D Repletion in Kidney Stone Formers: A Randomized Controlled Trial

Vitamin D deficiency is often detected during metabolic evaluation in the nephrolithiasis population. Multiple vitamin D repletion protocols exist, although their differing impact on urinary stone formation risk factors is unclear. Patients with a history of calcium stones and vitamin D deficiency (less than 30 ng/ml) were randomized to receive either 1,000 IU daily or 50,000 IU weekly of vitamin D supplementation for 6 weeks. Patients completed a pretreatment and posttreatment serum vitamin D level evaluation and 24-hour urine collections to assess the response and any changes in urine stone formation risk parameters. A total of 21 patients completed the study, including 8 who received 1,000 IU daily and 13 who received 50,000 IU weekly. The 50,000 IU weekly group showed a significant increase in median serum vitamin D levels of 23 ng/ml (135%, p <0.01), while the 1,000 IU daily group showed a nonsignificant median increase of 9 ng/ml (49%, p = 0.12). Post-repletion 24-hour urine analysis demonstrated no significant change in urine calcium between the groups, including a median change of -11 mg (IQR -143-29) in patients receiving 1,000 IU and -16 mg (IQR -42-66) in those receiving 50,000 IU. Between the groups there was no significant difference in the supersaturation of calcium oxalate or calcium phosphate. High dose and low dose vitamin D repletion had no effect on urine calcium excretion or the supersaturation of calcium salts in known stone formers. The higher dosing regimen, which had superior repletion, may be the optimal protocol in patients with vitamin D deficiency.

Risk of nephrolithiasis, hyperoxaluria, and calcium oxalate supersaturation increased after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis

BackgroundEarlier publications have shown renal stone complications after bariatric surgery. Multiple reports have also linked metabolic changes that alter the urinary chemistry profiles, especially hyperoxaluria, after bariatric surgery. However, evidence on change of other urine chemistry studies and type of bariatric surgery and risk of stone has been inconclusive so far. ObjectivesTo explore the association between bariatric surgery and postoperative urinary chemistry change and risk of stone formation SettingA systematic review and meta-analysis. MethodsWe comprehensively searched the databases of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from their dates of inception to January 2016. The inclusion criteria were published studies of association between bariatric surgery and postoperative renal stone formation or urine chemistry profiles. We used random-effects model meta-analysis and calculated the pooled risk of renal stone and difference in 24-hour urine chemistry profiles. ResultsTwelve observational studies were included in the meta-analysis. There was significantly higher risk of stone formation after Roux-en-Y gastric bypass surgery with pooled relative risk = 1.79 (95% CI: 1.54–2.10). In the analysis of urine chemistry profiles, there was significantly higher calcium oxalate supersaturation, lower citrate, and lower volume postoperatively compared with preoperatively. There was also higher urine oxalate in patients who had bariatric surgery compared with nonsurgery controls. ConclusionsRoux-en-Y gastric bypass surgery is associated with higher risk of renal stone and increased urine oxalate and calcium oxalate supersaturation.

Short-Term Tolvaptan Increases Water Intake and Effectively Decreases Urinary Calcium Oxalate, Calcium Phosphate and Uric Acid Supersaturations

Some patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should decrease urinary supersaturation of stone forming solutes, although this action has never been proved. We conducted a double-blind, randomized, placebo controlled, crossover study of 21 calcium urinary stone formers stratified into majority calcium oxalate (10 patients) and calcium phosphate (11) groups. Patients received 45 mg tolvaptan per day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24-hour urine sample was collected at the end of weeks 1 and 3. Tolvaptan vs placebo decreased urinary osmolality (mean ± SD 204 ± 96 vs 529 ± 213 mOsm/kg, p <0.001) and increased urinary volume (4.8 ± 2.9 vs 1.8 ± 0.9 L, p <0.001). The majority of urinary solute excretion rates, including sodium and calcium, did not change significantly, although oxalate secretion increased slightly (from mean ± SD 15 ± 8 to 23 ± 8 mg per 24 hours, p = 0.009). Mean ± SD urinary calcium oxalate supersaturation (-0.01 ± 1.14 vs 0.95 ± 0.87 dG, p <0.001), calcium phosphate supersaturation (-1.66 ± 1.17 vs -0.13 ± 1.02 dG, p <0.001) and uric acid supersaturation (-2.05 ± 4.05 vs -5.24 ± 3.12 dG, p=0.04) all dramatically decreased. Effects did not differ between the calcium oxalate and calcium phosphate groups (p >0.05 for all interactions). Tolvaptan increases urine volume and decreases urinary supersaturation in calcium stone formers. Further study is needed to determine if long-term use of V2 receptor antagonists results in fewer stone events.

Clinical, demographic, and laboratory characteristics of children with nephrolithiasis.

While the incidence of pediatric kidney stones appears to be increasing, little is known about the demographic, clinical, laboratory, imaging, and management variables in this patient population. We sought to describe various characteristics of our stone-forming pediatric population. To that end, we retrospectively reviewed the charts of pediatric patients with nephrolithiasis confirmed by imaging. Data were collected on multiple variables from each patient and analyzed for trends. For body mass index (BMI) controls, data from the general pediatrics population similar to our nephrolithiasis population were used. Data on 155 pediatric nephrolithiasis patients were analyzed. Of the 54 calculi available for analysis, 98% were calcium based. Low urine volume, elevated supersaturation of calcium phosphate, elevated supersaturation of calcium oxalate, and hypercalciuria were the most commonly identified abnormalities on analysis of 24-h urine collections. Our stone-forming population did not have a higher BMI than our general pediatrics population, making it unlikely that obesity is a risk factor for nephrolithiasis in children. More girls presented with their first stone during adolescence, suggesting a role for reproductive hormones contributing to stone risk, while boys tended to present more commonly at a younger age, though this did not reach statistical significance. These intriguing findings warrant further investigation.

National multi-institutional cooperative on urolithiasis in children: Age is a significant predictor of urine abnormalities

Pediatric nephrolithiasis is a growing problem and prior studies have shown the greatest increase in nephrolithiasis in the adolescent population. Metabolic abnormalities have historically been cited as the primary cause of pediatric nephrolithiasis; however, dietary and other factors such as obesity have also been studied with mixed results. We reviewed the charts of pediatric patients with a history of nephrolithiasis to determine the number and types of metabolic abnormalities present on 24-h urine analysis. We retrospectively reviewed the charts of all pediatric patients with a history of nephrolithiasis from 1999-2013 across four different institutions. The subjects were excluded if they had a history of spina bifida, neurogenic bladder, cerebral palsy, isolated bladder stones, or if they were on medical therapy for nephrolithiasis before the first 24-h urine collection. There were 206 subjects included in the analysis with an average age of 13 (±3.9) years. The patients were stratified into two age groups based on an apparent bimodal distribution of metabolic abnormalities, ≤10 years and >10 years of age. Metabolic abnormalities were present in 130 children (63.1%) and there was a difference between the groups, with children ≤10 years more likely to have a metabolic abnormality compared with those >10 years of age (75% vs. 60.6%, p = 0.0443) on univariate analysis. In children ≤10 years hypercalciuria was the most common disorder present (48.4%), and in children >10 years hypocitraturia was the most common disorder present (26.1%). Children ≤10 years of age were more likely to have normal volume (p = 0.006), elevated urinary oxalate (p = 0.0351), elevated urinary calcium (p < 0.001), elevated supersaturation of calcium phosphate (p < 0.001), and elevated supersaturation of calcium oxalate (p = 0.002). On multivariate analysis, children ≤10 years of age were more likely to have normal volume, hyperoxaluria, elevated supersaturation of calcium phosphate and a trend towards hypercalciuria (Table). Our study reveals that younger children are more likely to have a metabolic abnormality present on 24-h urine analysis. This has important implications when deciding on treatment options, with younger children potentially requiring more aggressive management with medical therapy. Older children were more likely to have low urinary volume and their most common metabolic abnormality was hypocitraturia. Although dietary factors have not been established as the definitive reason behind the rising incidence of nephrolithiasis in the adolescent population, older children may benefit more from diet modification with a strong focus on increasing volume intake. We found differences in younger compared with older age groups in terms of the number and types of metabolic disorders present. Children ≤10 years of age were more likely to have a metabolic disorder including elevations in calcium, oxalate and supersaturation of calcium phosphate, while children >10 years of age were more likely to have low urinary volume. These differences have important implications for future investigative studies on the rising incidence as well as the best course of treatment for children with nephrolithiasis.

Stone formation and management after bariatric surgery.

Obesity is a significant health concern and is associated with an increased risk of nephrolithiasis, particularly in women. The underlying pathophysiology of stone formation in obese patients is thought to be related to insulin resistance, dietary factors, and a lithogenic urinary profile. Uric acid stones and calcium oxalate stones are common in these patients. Use of surgical procedures for obesity (bariatric surgery) has risen over the past two decades. Although such procedures effectively manage obesity-dependent comorbidities, several large, controlled studies have revealed that modern bariatric surgeries increase the risk of nephrolithiasis by approximately twofold. In patients who have undergone bariatric surgery, fat malabsorption leads to hyperabsorption of oxalate, which is exacerbated by an increased permeability of the gut to oxalate. Patients who have undergone bariatric surgery show characteristic 24 h urine parameters including low urine volume, low urinary pH, hypocitraturia, hyperoxaluria and hyperuricosuria. Prevention of stones with dietary limitation of oxalate and sodium and a high intake of fluids is critical, and calcium supplementation with calcium citrate is typically required. Potassium citrate is valuable for treating the common metabolic derangements as it raises urinary pH, enhances the activity of stone inhibitors, reduces the supersaturation of calcium oxalate, and corrects hypokalaemia. Both pyridoxine and probiotics have been shown in small studies to reduce hyperoxaluria, but further study is necessary to clarify their effects on stone morbidity in the bariatric surgery population.

MP41-08 RANDOMIZED CONTROLLED TRIAL OF TWO VITAMIN D REPLETION PROTOCOLS TO ASSESS IMPACT ON CALCIUM EXCRETION IN STONE FORMERS

You have accessJournal of UrologyStone Disease: Medical Therapy1 Apr 2015MP41-08 RANDOMIZED CONTROLLED TRIAL OF TWO VITAMIN D REPLETION PROTOCOLS TO ASSESS IMPACT ON CALCIUM EXCRETION IN STONE FORMERS Matthew Ferroni, Kevin Rycyna, Timothy Averch, and Michelle Semins Matthew FerroniMatthew Ferroni More articles by this author , Kevin RycynaKevin Rycyna More articles by this author , Timothy AverchTimothy Averch More articles by this author , and Michelle SeminsMichelle Semins More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1636AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It is estimated that up to 90% of Americans have insufficient vitamin D levels which may have significant impact on a variety of chronic illnesses including cardiovascular disease and bone health. Over-repletion of vitamin D, however, may be a potential risk factor for nephrolithiasis, particularly in known stone formers, as it may be associated with hypercalciuria. A variety of accepted standard vitamin D repletion protocols exist, however their differing impact on urinary stone formation risk factors is unclear. METHODS Patients with a previous history of stone formation and who were found to have vitamin D insufficiency (<30ng/ml) on initial metabolic workup were randomized to receive vitamin D repletion with either 1,000 IU daily or 50,000 IU per week for a total of 6 weeks. All patients completed a pre-repletion 24-hour urine collection to assess their baseline stone formation risk parameters as well as post-repletion 24-urine collection to evaluate any changes. Patients also had serum vitamin D levels drawn before and after repletion. Statistical analysis was performed using Wilcoxon rank-sum tests and all data reported are median values with 95% confidence intervals. RESULTS 20 patients completed the study; 8 who received 1,000 IU daily and 12 who received 50,000 IU weekly. Patients receiving 50,000 IU showed significant improvement in serum vitamin D levels with a delta of 23ng/ml (144% increase, p<0.01) over pre-repletion level, while patients receiving 1,000 IU daily showed a non-significant delta of 8ng/ml (45% increase, p=0.14). The difference between the groups was also significant, p=0.04. Post-repletion 24-hour urine analysis showed no significant change in urine calcium among both groups; median change of -45.5mg in patients receiving 1,000 IU (-188, 29, p=0.34) and -10.3mg in those receiving 50,000 IU (-53.5, 81.7, p=0.82), or between them, p=0.44. Between the groups there was also no significant difference in either the super-saturation of calcium oxalate (changes of -1.28 and 0.8, p=0.23) or the calcium phosphate (changes of -0.65 and 0.5, p=0.28). CONCLUSIONS Neither dose of vitamin D supplementation increased urine calcium or the super-saturation of calcium salts in known stone formers. Based on the superior improvement in serum vitamin D levels in patients receiving 50,000 IU weekly, this regimen may be an effective treatment choice in stone formers who present with vitamin D insufficiency. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e502-e503 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Ferroni More articles by this author Kevin Rycyna More articles by this author Timothy Averch More articles by this author Michelle Semins More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...