Real-World Effectiveness of Preventive Pharmacological Therapy in Patients With Urolithiasis: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Data supporting the efficacy of preventive pharmacological therapy (PPT) to reduce urolithiasis recurrence are based on clinical trials with composite outcomes that incorporate imaging findings and have uncertain clinical significance. This study evaluated whether the use of PPT leads to fewer symptomatic stone events. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Medicare enrollees with urolithiasis who completed 24-hour urine collections that revealed hypercalciuria, hypocitraturia, low urine pH, or hyperuricosuria. EXPOSURE: PPT (thiazide diuretics for hypercalciuria, alkali for hypocitraturia or low urine pH, or uric acid lowering drugs for hyperuricosuria) categorized as (1) adherent to guideline-concordant PPT, (2) nonadherent to guideline-concordant PPT, or (3) untreated. OUTCOME: Symptomatic stone event occurrence (emergency department [ED] visit or hospitalization for urolithiasis or stone-directed surgery). ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: Among 13,942 patients, 31.0% were prescribed PPT. Compared with no treatment, concordant/adherent PPT use was associated with a significantly lower hazard of symptomatic stone events for patients with hypercalciuria (HR, 0.736 [95% CI, 0.593-0.915]) and low urine pH (HR, 0.804 [95% CI, 0.650-0.996]) but not for patients with hypocitraturia or hyperuricosuria. These associations were largely driven by significantly lower rates of ED visits after initiating PPT among the concordant/adherent group versus untreated patients. Patients with hypercalciuria had adjusted 2-year predicted probabilities of a visit of 3.8% [95% CI, 2.5%-5.2%%] and 6.9% [95% CI, 6.0%-7.7%] for the concordant/adherent PPT and no-treatment groups, respectively. Among patients with low urine pH, these probabilities were 4.3% (95% CI, 2.9%-5.7%) and 7.3% (95% CI, 6.5%-8.0%) for the concordant/adherent PPT and no-treatment groups, respectively. LIMITATIONS: Potential bias from the possibility that patients prescribed PPT had more severe disease than untreated patients. CONCLUSIONS: Patients with urolithiasis and hypercalciuria who were adherent to treatment with thiazide diuretics as well as those with low urine pH adherent to prescribed alkali therapy had fewer symptomatic stone events than untreated patients. PLAIN-LANGUAGE SUMMARY: Despite multiple clinical trials demonstrating the efficacy of thiazide diuretics and alkali for secondary prevention of kidney stones, they are infrequently prescribed due in part to a lack of data about their effectiveness in real-world settings. We analyzed medical claims from older adults with kidney stones for whom urine chemistry data were available. We found that patients who took prescribed thiazide diuretics for elevated urine calcium levels or alkali for low urinary pH were less likely to experience symptomatic stone recurrences than untreated patients. This benefit was expressed as lower rates of emergency department visits after initiating therapy. Our findings should inform the prescription of and adherence to treatment with thiazide diuretics and alkali for the prevention of recurrent kidney stones.

Alkaline Water: Help or Hype for Uric Acid and Cystine Urolithiasis?

PURPOSE: The consumption of alkaline water, water with an average pH of 8 to 10, has been steadily increasing globally as proponents claim it to be a healthier alternative to regular water. Urinary alkalinization therapy is frequently prescribed in patients with uric acid and cystine urolithiasis, and as such we analyzed commercially available alkaline waters to assess their potential to increase urinary pH. MATERIALS AND METHODS: Five commercially available alkaline water brands (Essentia, Smart Water Alkaline, Great Value Hydrate Alkaline Water, Body Armor SportWater, and Perfect Hydration) underwent anion chromatography and direct chemical measurements to determine the mineral contents of each product. The alkaline content of each bottle of water was then compared to that of potassium citrate (the gold standard for urinary alkalinization) as well as to other beverages and supplements used to augment urinary citrate and/or the urine pH. RESULTS: The pH levels of the bottled alkaline water ranged from 9.69 to 10.15. Electrolyte content was minimal, and the physiologic alkali content was below 1 mEq/L for all brands of alkaline water. The alkali content of alkaline water is minimal when compared to common stone treatment alternatives such as potassium citrate. In addition, several organic beverages, synthetic beverages, and other supplements contain more alkali content than alkaline water, and can achieve the AUA and European Association of Urology alkali recommendation of 30 to 60 mEq per day with ≤ 3 servings/d. CONCLUSIONS: Commercially available alkaline water has negligible alkali content and thus provides no added benefit over tap water for patients with uric acid and cystine urolithiasis.

First Reported Case of a Pyrophosphate Kidney Stone in a Human.

Urolithiasis composed of pyrophosphate salts has only been reported in animals, in the form of potassium magnesium pyrophosphate. However, there have been no reports of pyrophosphate stones in humans. Hypophosphatasia is an inherited disease characterized by low alkaline phosphatase activity and elevated levels of pyrophosphate in blood and urine. Urolithiasis is a part of the hypophosphatasia phenotype. The role of elevated urine pyrophosphate levels in the formation of stones in hypophosphatasia is unknown. Here, we report a case of a 60-year-old man with recurrent urolithiasis. The patient's most recent presentation was gross hematuria and his computed tomography scan showed bilateral kidney stones. Stones were removed via retrograde intrarenal surgery. Stone analysis revealed a composition of potassium magnesium pyrophosphate. The patient also has a long history of fracturing bone disease which led to the consideration of hypophosphatasia as the cause of both his bone disease and pyrophosphate stones. Hypophosphatasia was confirmed by genetic analysis. Pyrophosphate has been of interest in the fields of mineral metabolism because of its action as a crystallization inhibitor. However, pyrophosphate at elevated concentrations in the presence of divalent cations can exceed its solubility. Nephrocalcinosis and stone disease have been described in hypophosphatasia; stones have been assumed to be calcium phosphate but no compositional analysis has been reported. This is the first report of human stones composed of pyrophosphate salts, which led to the subsequent diagnosis of hypophosphatasia in this patient.

Effect of a high-citrate beverage on urine chemistry in patients with calcium kidney stones.

A well-accepted strategy to prevent kidney stones is to increase urine volume by increasing oral intake of fluids, especially water, to lower supersaturation of the relevant, relatively insoluble salts, and thereby lower the risk of precipitation. Randomized controlled trials have shown that this strategy works. It is inexpensive, safe, and intuitively attractive to patients. However, although any beverage can increase urine volume, and citrus juices can increase urine citrate content and pH, no beverage other than water has been clearly shown by randomized controlled trial to prevent kidney stones. We designed an innovative, palatable, low-calorie, high alkali citrate beverage to prevent kidney stones, called Moonstone. One packet of Moonstone powder, mixed in 500 ml of water, contains 24.5 meq of alkali citrate. We administered one packet twice a day to ten calcium stone formers. Moonstone resulted in an increase in mean 24-h urine citrate and urine pH, and a decrease in supersaturation of calcium oxalate in calcium stone formers compared to an equal volume of water. These changes, comparable to those seen in a prior study of a similar amount of (potassium-magnesium) citrate, will likely be associated with a clinically meaningful reduction in kidney stone burden in patients with calcium stones. The effect to increase urine pH would also be expected to benefit patients with uric acid and cystine stones, groups that we hope to study in a subsequent study. The study preparation was well tolerated and was selected as a preferred preventative strategy by about half the participants. Moonstone is an alternative, over-the-counter therapy for kidney stone prevention.

Sex Differences of Kidney Stone Urine Risk Factors after Roux-en-Y Gastric Bypass.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) is a bariatric surgical procedure that is associated with higher risk of kidney stones after surgery. We examined urine composition in 18 men and women before and after RYGB to examine differences in kidney stone risk. METHODS: Three 24-h urine collections were performed before and 1 year after RYGB. We analyzed mean urinary values for pre- and post-RYGB collections and compared men and women. RESULTS: Seven men and eleven women completed pre- and post-RYGB urine collections. Pre-RYGB, men had higher calcium oxalate supersaturation (CaOx SS) (7.0 vs. 5.0, p = 0.04) compared with women. Post-RYGB, women had higher urine CaOx SS (13.1 vs. 4.6, p = 0.002), calcium phosphate supersaturation (1.04 vs. 0.59, p = 0.05), and lower urine volumes (1.7 vs. 2.7L, p < 0.001) compared with men. DISCUSSION/CONCLUSION: There are important differences in urine composition by sex that may contribute to higher kidney stone risk in women after RYGB compared with men.

Nephrolithiasis and Elevated Urinary Ammonium: A Matched Comparative Study.

OBJECTIVE: To describe the associations between elevated urinary ammonium and clinical characteristics of kidney stone formers. A 24-hour urine test is recommended in high-risk patients to identify urinary abnormalities and select interventions to reduce the recurrence risk. While elevations in urine ammonium may be seen in acidosis, diarrhea, high protein diets or due to pathogenic bacteria, the clinical characteristics of these patients have not been previously described. METHODS: We retrospectively identified adult patients with kidney stone disease who completed a 24-hour urine at our institution between 2006 and 2017. Patients with elevated urinary ammonium were identified (n = 121) and matched 1:1 by age and sex to controls for an overall cohort of n = 242. Differences in medical and surgical history, 24-hour urine analytes and stone composition were compared. RESULTS: Among 3625 24-hour urine studies screened, 7.1% of patients showed high urinary ammonium. In our study cohort, patients with elevated urinary ammonium also showed higher urine volume, oxalate, calcium, uric acid, sodium, chloride, and sulfate. Clinically, these patients had higher body mass index, and more often had a history of recurrent urinary tract infections, diabetes, gout, bowel resection, and urinary reconstruction history. Struvite stones tended to be more common in the elevated ammonium group vs control (n = 7 vs 1, P = .07). CONCLUSION: Elevated urinary ammonium among kidney stone patients is relatively uncommon. However, these patients have higher rates of comorbid metabolic conditions, urinary tract infections, and bowel surgery. This finding should prompt further review of the patient's history and may help direct prevention strategies.

A laboratory-based algorithm to predict future kidney function decline in older adults with reduced estimated glomerular filtration rate
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BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) in older adults is common and may reflect normal aging or significant kidney disease. Our objective was to develop a predictive model to better triage these individuals using routine laboratory data. MATERIALS AND METHODS: Using a large US laboratory data set, we calculated individual eGFR regression slopes for 43,523 individuals aged 60 - 75 years with baseline eGFRs between 30 and 59 mL/min/1.73m2. We developed general linear models to predict the eGFR regression slope using urine protein measurements and other routinely available laboratory data as dependent variables. We validated these models on a similar data set comprised of 11,979 individuals. RESULTS: In a model utilizing log10 urine albumin/creatinine (UACR), the variables that significantly predicted the eGFR regression slope were log10 UACR, initial eGFR, serum albumin, chloride, glucose, and aspartate aminotransferase (AST). In an otherwise identical model substituting log10 urine protein/creatinine (UPCR) for UACR, results were similar except that serum calcium was significant and AST was not. We analyzed the correspondence between actual eGFR regression slopes and those predicted by our models using receiver operator characteristic (ROC) statistics to calculate areas under the curves (AUC) for four eGFR slope cut points: -2, -3, -4, and -5 mL/min/year. AUCs using the UACR and UPCR models ranged from 0.716 to 0.900 and 0.751 to 0.868, respectively, for the training data set. Results were nearly identical for the validation data set. CONCLUSION: Use of a laboratory-based predictive model of eGFR decline for older adults with eGFR 30 - 59 mL/min/1.73m2 may help distinguish between individuals with and without risk for further decline in kidney function.

Effect of increasing doses of cystine-binding thiol drugs on cystine capacity in patients with cystinuria.

Appropriate dosing of cystine-binding thiol drugs in the management of cystinuria has been based on clinical stone activity. When new stones form, the dose is increased. Currently, there is no method of measuring urinary drug levels to guide the titration of therapy. Increasing cystine capacity, a measure of cystine solubility, has been promoted as a method of judging the effects of therapy. In this study, we gave increasing doses of tiopronin or D-penicillamine, depending on the patients' own prescriptions, to ten patients with cystinuria and measured cystine excretion and cystine capacity. The doses were 0, 1, 2, 3 g per day, given in two divided doses, and administered in a random order. Going from 0 to 1 g/day led to an increase in cystine capacity from - 39.1 to 130.4 mg/L (P < 0.009) and decreased 24 h cystine excretion from 1003.9 to 834.8 mg/day (P = 0.039). Increasing the doses from 1 to 2 to 3 g/day had no consistent or significant effect to further increase cystine capacity or decrease cystine excretion. Whether doses higher than 1 g/day have additional clinical benefit is not clear from this study. Limiting doses might be associated with fewer adverse effects without sacrificing the benefit of higher doses if higher doses do not offer clinical importance. However, trials with stone activity as an outcome would be desirable.

Individual renal unit urine sampling to identify unilateral metabolic defects
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AIMS: Preventing kidney stone recurrence relies on detecting and modifying urine chemistry abnormalities. The assumption is that an abnormality is due to a global metabolic defect present in both kidneys. However, we hypothesize that clinically significant unilateral defects may exist. We aimed to identify these patients by sampling urine from each renal unit. MATERIALS AND METHODS: Adults undergoing retrograde upper urinary tract surgery were eligible for inclusion. Excluded were patients with a solitary kidney, suspected urothelial malignancy, or urinary tract infection. Following informed consent, all patients proceeded to the operating room. After induction of anesthesia, cystoscopy with ureteral catheterization was performed with urine collected via gravity drainage for 10 minutes. Urine samples with adequate volume were analyzed for chemistry concentrations. A difference greater than the 75th percentile between matched pairs was considered significant. For urine pH, a difference of 0.5 was considered significant. RESULTS: A total of 47 patients were screened for eligibility with only 13 (28%) electing to enroll in the study (26 renal units). All subjects underwent successful bilateral ureteral catheterization with no adverse events observed or later reported. The mean (± SD) urine volume captured from the right and left renal units was 5.0 ± 7.4 cm3 and 6.6 ± 6.4 cm3, respectively. Urine was only captured from paired renal units in 8 participants (8/13; 62%). Of these 8 participants, 5 (5/8; 63%) had at least 1 unilateral metabolic defect. CONCLUSION: Unilateral renal unit urine sampling is safe and feasible. However, captured urine volumes are small and variable, but chemical analysis can still be performed. Unilateral defects in renal electrolyte handling are relatively common, but the clinical implications of these differences are still yet to be determined.
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Urine kidney injury markers do not increase following gastric bypass: a multi-center cross-sectional study.

INTRODUCTION: To determine if markers of kidney injury correlate with urinary oxalate excretion. If so, such biomarkers might be early predictors of oxalate nephropathy. Gastric bypass surgery for obesity is known to be associated with postoperative hyperoxaluria, which can lead to urolithiasis and kidney damage. MATERIALS AND METHODS: Patients were recruited from four 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 F2 α, N-acetyl- ß -D-Glucosaminidase, and Neutrophil gelatinase-associated lipocalin. Patients also provided 24 hour urine samples for stone risk analysis. RESULTS: A total of 46 study patients provided samples, 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. 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.

Evidence for a role of PDZ domain-containing proteins to mediate hypophosphatemia in calcium stone formers.

Background: Hypophosphatemia (HYP) is common among calcium stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP. Methods: To test this idea, we analyzed two large but separate sets of 24-h urine samples and paired serums of 2700 SFs from the University of Chicago and 11 073 SFs from Litholink, a national laboratory. Patients were divided into quintiles based on serum phosphate. Results: Males were more common in the lowest phosphate tiles in both datasets. Phosphate excretion did not vary across the quintiles, excluding diet as a cause of HYP. Tubule maximum (Tm) phosphate per unit glomerular filtration rate decreased and fractional excretion increased with decreasing phosphate quintiles, indicating reduced tubule phosphate reabsorption was responsible for HYP. Urine pH and serum chloride increased with decreasing serum phosphate, suggesting a coordinate change in NHE3 activity. Serum uric acid and Tm uric acid decreased significantly with decreasing serum phosphate, while uric acid excretion did not vary. Conclusion. HYP in SFs results from decreased tubule phosphate reabsorption and, being associated with related changes in other proximal tubule transporters, may arise from alterations in or signaling to PDZ-containing proteins.

Steatorrhea and Hyperoxaluria in Severely Obese Patients Before and After Roux-en-Y Gastric Bypass.

BACKGROUND AND AIMS: Hyperoxaluria after Roux-en-Y gastric bypass (RYGB) is generally attributed to fat malabsorption. If hyperoxaluria is indeed caused by fat malabsorption, magnitudes of hyperoxaluria and steatorrhea should correlate. Severely obese patients, prior to bypass, ingest excess dietary fat that can produce hyperphagic steatorrhea. The primary objective of the study was to determine whether urine oxalate excretion correlates with elements of fat balance in severely obese patients before and after RYGB. METHODS: Fat balance and urine oxalate excretion were measured simultaneously in 26 severely obese patients before and 1 year after RYGB, while patients consumed their usual diet. At these time points, stool and urine samples were collected. Steatorrhea and hyperoxaluria were defined as fecal fat >7 g/day and urine oxalate >40 mg/day. Differences were evaluated using paired 2-tailed t tests. RESULTS: Prior to RYGB, 12 of 26 patients had mild to moderate steatorrhea. Average urine oxalate excretion was 61 mg/day; there was no correlation between fecal fat and urine oxalate excretion. After RYGB, 24 of 26 patients had steatorrhea and urine oxalate excretion averaged 69 mg/day, with a positive correlation between fecal fat and urine oxalate excretions (r = 0.71, P < .001). For each 10 g/day increase in fecal fat output, fecal water excretion increased only 46 mL/day. CONCLUSIONS: Steatorrhea and hyperoxaluria were common in obese patients before bypass, but hyperoxaluria was not caused by excess unabsorbed fatty acids. Hyperphagia, obesity, or metabolic syndrome could have produced this previously unrecognized hyperoxaluric state by stimulating absorption or endogenous synthesis of oxalate. Hyperoxaluria after RYGB correlated with steatorrhea and was presumably caused by excess fatty acids in the intestinal lumen. Because post-bypass steatorrhea caused little increase in fecal water excretion, most patients with steatorrhea did not consider themselves to have diarrhea. Before and after RYGB, high oxalate intake contributed to the severity of hyperoxaluria.

Oxalobacter formigenes-Derived Bioactive Factors Stimulate Oxalate Transport by Intestinal Epithelial Cells.

Hyperoxaluria is a major risk factor for kidney stones and has no specific therapy, although Oxalobacter formigenes colonization is associated with reduced stone risk. O. formigenes interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion, via an unknown secretagogue. The difficulties in sustaining O. formigenes colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of O. formigenes culture conditioned medium (CM) on apical 14C-oxalate uptake by human intestinal Caco-2-BBE cells. Compared with control medium, O. formigenes CM significantly stimulated oxalate uptake (>2.4-fold), whereas CM from Lactobacillus acidophilus did not. Treating the O. formigenes CM with heat or pepsin completely abolished this bioactivity, and selective ultrafiltration of the CM revealed that the O. formigenes-derived factors have molecular masses of 10-30 kDa. Treatment with the protein kinase A inhibitor H89 or the anion exchange inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid completely blocked the CM-induced oxalate transport. Knockdown of the oxalate transporter SLC26A6 also significantly restricted the induction of oxalate transport by CM. In a mouse model of primary hyperoxaluria type 1, rectal administration of O. formigenes CM significantly reduced (>32.5%) urinary oxalate excretion and stimulated (>42%) distal colonic oxalate secretion. We conclude that O. formigenes-derived bioactive factors stimulate oxalate transport in intestinal cells through mechanisms including PKA activation. The reduction in urinary oxalate excretion in hyperoxaluric mice treated with O. formigenes CM reflects the in vivo retention of biologic activity and the therapeutic potential of these factors.

Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr-/- mice in Ussing chambers and measured transcellular secretion of [14C]oxalate. Intestinal tissue isolated from Cftr-/- mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr-/- tissue. Compared with wild-type mice, Cftr-/- mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl--oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr-/- mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis.

Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease.

Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.

The role of the 24-h urine collection in the management of nephrolithiasis.

Recurrent nephrolithiasis is a common chronic condition that is often preventable with dietary modification and pharmacologic therapy. Patients with recurrent kidney stones should have a metabolic evaluation, consisting of radiologic studies to assess stone burden, crystallographic stone analysis, and laboratory studies including standard serum chemistries and 24 h urine collection(s). This article focuses on the interpretation of urine chemistries to identify lithogenic risk factors and assess the contribution of diet to the formation of kidney stones.

Prospective evaluation of urinary metabolic indices in severely obese adolescents after weight loss surgery.

BACKGROUND: Observational studies in obese adults have found abnormal urinary metabolic indices that predispose to nephrolithiasis. Few studies have been performed in severely obese adolescents. OBJECTIVES: To assess urinary stone risk factors in severely obese adolescents and in those undergoing 2 types of weight loss surgery. SETTING: Children's hospital, United States. METHODS: A prospective cross-sectional study was performed to assess urinary metabolic profiles in severely obese adolescents who either have not undergone any gastrointestinal surgery or who have undergone Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (SG). Twenty-four-hour urine collections were performed at home and evaluated at a central laboratory. Established normal reference ranges for adults were used in the analysis. A linear regression analysis was performed assessing the relationship of the study group with each of the outcomes. RESULTS: A total of 55 samples were analyzed from 14 severely obese adolescents and from 17 severely obese adolescents after bariatric surgery (RYGB, 10; SG, 7). Median body mass index was similar between the RYGB and SG groups. The median 24-hour excretion of oxalate was significantly elevated in the RYGB group. Calcium and uric acid excretion and the median supersaturation of calcium oxalate, calcium phosphate, and uric acid were similar among all groups. CONCLUSIONS: Elevated excretion of oxalate in the urine of severely obese adolescents and in those who have undergone RYGB may portend increased risk for kidney stone formation. Larger longitudinal studies are needed to verify these findings and to determine the clinical risk of developing stone disease in these patient populations.

The management of patients with enteric hyperoxaluria.

Enteric hyperoxaluria is a common occurrence in the setting of fat malabsorption, usually due to intestinal resection or intestinal bypass surgery. Enhanced intestinal absorption of dietary oxalate leads to elevated renal oxalate excretion, frequently in excess of 100 mg/d (1.14 mmol/d). Patients are at increased risk of urolithiasis and loss of kidney function from oxalate nephropathy. Fat malabsorption causes increased binding of diet calcium by free fatty acids, reducing the calcium available to precipitate diet oxalate. Delivery of unabsorbed bile salts and fatty acids to the colon increases colonic permeability, the site of oxalate hyper-absorption in enteric hyperoxaluria. The combination of soluble oxalate in the intestinal lumen and increased permeability of the colonic mucosa leads to hyperoxaluria. Dietary therapy consists of limiting oxalate and fat intake. The primary medical intervention is the use of oral oxalate binding agents such as calcium salts to reduce free intestinal oxalate levels. Bile acid sequestrants can be useful in patients with ileal resection and bile acid malabsorption. Oxalate degrading bacteria provided as probiotics are being investigated but as of yet, no definite benefit has been shown with currently available preparations. The current state of medical therapy and potential future directions will be summarized in this article.

Struvite urolithiasis and chronic urinary tract infection in a murine model of urinary diversion.

OBJECTIVE: To characterize the clinical course after cutaneous vesicostomy (CV) in megabladder (mgb(-/-)) mice with functional urinary bladder obstruction. MATERIALS AND METHODS: A total of 45 mgb(-/-) male mice underwent CV at a median age of 25 days. The 34 mice that survived >3 days after CV were evaluated by serial observation and renal ultrasonography. The moribund mice were killed. The urinary bladders and kidneys were analyzed by histopathologic analysis, and urine biochemical studies were performed. RESULTS: At a median duration of 11 weeks after CV, 35% of mgb(-/-) male mice (12 of 34) had become moribund with pelvic masses, which were identified as bladder stones at necropsy. The urine pH was alkaline, and microscopic examination demonstrated struvite crystals. The urine samples contained Gram-positive cocci, and the urine cultures were polymicrobial. The stone composition was chiefly struvite (88%-94%) admixed with calcium phosphate. In 40% of cases (2 of 5), retained intravesical polypropylene suture was identified as the presumed nidus. No stones were detected in >100 male mice before CV or in 25 cases when CV was performed using polydioxanone suture. The kidneys from 33% of the mice (4/12) with bladder stones contained staghorn calculi. The histopathologic findings from the mice with struvite stones demonstrated active cystitis, pyelitis, and chronic pyelonephritis. CONCLUSION: These findings attest to the importance of the nidus in lithogenesis and provide a novel murine model for struvite urolithiasis and chronic infection of the diverted urinary tract.