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.

Complementary and Alternative Medicine Use in First-time and Recurrent Kidney Stone Formers.

OBJECTIVE: To describe the patterns of complementary and alternative medicine (CAM) among patients with kidney stones and analyze the alkali content of commonly used CAM therapies. METHODS: We prospectively conducted structured interviews with patients who presented to a specialty stone clinic for the management of kidney stones. Open-ended questions were used to elicit information regarding CAM knowledge, formulation/dosing, and patterns of use. Several common CAM therapies were then analyzed for their alkali, organic anion, and sugar content. RESULTS: Of 103 subjects, 82 (80%) patients reported knowledge of CAM and 52 (50%) reported using CAM. Patients with recurrent kidney stones were more likely to report using CAM than patients with first-time episodes (56% vs 26%, P = 0.04). Some respondents reported their condition decreased in severity or frequency since starting CAM therapy (17%) and improvements in pain (12%). Total alkali content per serving of the tested supplements was 0 mEq (Stonebreaker), 1.5 mEq (Ocean Spray Cranberry Juice Cocktail), 4.7 mEq (Lakewood Pure Cranberry Juice), 0.6 mEq (Braggs Apple Cider Vinegar), 11.9 mEq (LithoBalance), 9.5 mEq (Simply Grapefruit Juice), 19.8 mEq (KSP-Key Lime), and 20.2 mEq (KSP-Very Berry). CONCLUSION: Patients with kidney stones may use CAM to alleviate symptoms or prevent recurrence. Commercially available CAM therapies may contain comparable alkali content to commonly prescribed citrate therapy. These data suggest that providers should be prepared to discuss the role of CAM with their patients.

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.

Using Low-Calorie Orange Juice as a Dietary Alternative to Alkali Therapy.

Purpose: The pursuit of a dietary source to increase urine pH and citrate in stone formers has been ongoing for >30 years. Early evidence showed that orange juice (OJ) contains alkali and citrate, but high sugar and ascorbic acid content limited the use of OJ as a viable daily source of alkali. Recently, novel low-calorie OJs have emerged and could potentially be a better option. Methods: Beverages with high concentrations of alkali citrate and malate were identified using ion chromatography. Two low-calorie OJ beverages, in addition to crystal light lemonade beverage (CLLB), were chosen. Healthy volunteers (5 men, 5 women) drank 1 L of OJ or CLLB with 1 L water daily for 7 days, and then completed a 24-hour urinalysis. A washout week was instituted between trial weeks. The study design is a prospective randomized crossover control trial. A paired analysis using comparison of means was used to evaluate low-calorie OJ and CLLB. Volunteers had no prior history of kidney stones and maintained a journal with beverage compliance, side effect (SE), and dietary consumption data. Results: Tropicana 50 (TRP50), Kroger low-calorie OJ (KLCO), and CLLB were found to have a total alkali content of 56.60, 47.9, and 17.3 mEq/L, respectively, based on ion chromatography. Consumption of all three beverages raised urinary citrate (116.6 [-118 to 373, 177.9 [-3 to 359], 155.6 [-4 to 237] ▵mg/day 95% confidence interval) and urinary pH (0.25 [0.08-0.53], 0.74 [0.41-1.07 p < 0.05], 0.25 [0.25-0.64]), respectively, compared with water phase. Based on journal entries by volunteers, TRP50 had the most SEs (90% participants) felt to be a result of the artificial sweetener (Stevia®). Conclusion: Low-calorie OJs, and to a lesser extent CLLB, have alkali and citrate based on ion chromatography. Daily consumption by healthy volunteers of KLCO can raise urinary pH.

Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats.

BACKGROUND: The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats. METHODS: To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks. RESULTS: Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not. CONCLUSIONS: In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.

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.

Acid Load and Phosphorus Homeostasis in CKD.

BACKGROUND: The kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) in vitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTORS: Net acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimated from food frequency questionnaire responses, and serum bicarbonate concentration < 22 mEq/L. OUTCOME & MEASUREMENTS: 24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations. RESULTS: Using linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P<0.05). Serum phosphorus concentration was also higher with higher net acid excretion and lower serum bicarbonate concentration (each P=0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion (P<0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but not FGF-23, concentration (P=0.2) was 26% (95% CI, 13%-40%) higher in participants with a serum bicarbonate concentration <22 versus ≥22 mEq/L (P<0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n=359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available. LIMITATIONS: Possible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion. CONCLUSIONS: In CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials.

Clinical decision support improves physician guideline adherence for laboratory monitoring of chronic kidney disease: a matched cohort study.

BACKGROUND: Guidelines exist for chronic kidney disease (CKD) but are not well implemented in clinical practice. We evaluated the impact of a guideline-based clinical decision support system (CDSS) on laboratory monitoring and achievement of laboratory targets in stage 3-4 CKD patients. METHODS: We performed a matched cohort study of 12,353 stage 3-4 CKD patients whose physicians opted to receive an automated guideline-based CDSS with CKD-related lab results, and 42,996 matched controls whose physicians did not receive the CDSS. Physicians were from US community-based physician practices utilizing a large, commercial laboratory (LabCorp®). We compared the percentage of laboratory tests obtained within guideline-recommended intervals and the percentage of results within guideline target ranges between CDSS and non-CDSS patients. Laboratory tests analyzed included estimated glomerular filtration rate, plasma parathyroid hormone, serum calcium, phosphorus, 25-hydroxy vitamin D (25-D), total carbon dioxide, transferrin saturation (TSAT), LDL cholesterol (LDL-C), blood hemoglobin, and urine protein measurements. RESULTS: Physicians who used the CDSS ordered all CKD-relevant testing more in accord with guidelines than those who did not use the system. Odds ratios favoring CDSS ranged from 1.29 (TSAT) to 1.88 (serum phosphorus) [CI, 1.20 to 2.01], p < 0.001 for all tests. The CDSS impact was greater for primary care physicians versus nephrologists. CDSS physicians met guideline targets for LDL-C and 25-D more often, but hemoglobin targets less often, than non-CDSS physicians. Use of CDSS did not impact guideline target achievement for the remaining tests. CONCLUSIONS: Use of an automated laboratory-based CDSS may improve physician adherence to guidelines with respect to timely monitoring of CKD.

Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria.

Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation.

1,25(OH)2D3 induces a mineralization defect and loss of bone mineral density in genetic hypercalciuric stone-forming rats.

Genetic hypercalciuric stone-forming (GHS) rats, bred to maximize urine (u) calcium (Ca) excretion, demonstrate increased intestinal Ca absorption, increased bone Ca resorption, and reduced renal Ca reabsorption, all leading to elevated uCa compared to the parental Sprague-Dawley (SD) rats. GHS rats have increased numbers of vitamin D receptors (VDRs) at each site, with normal levels of 1,25(OH)2D3 (1,25D), suggesting their VDR is undersaturated with 1,25D. We have shown that 1,25D induces a greater increase in uCa in GHS than SD rats. To examine the effect of the increased VDR on the osseous response to 1,25D, we fed GHS and SD rats an ample Ca diet and injected either 1,25D [low dose (LD) 12.5 or high dose (HD) 25 ng/100 g body weight/day] or vehicle (veh) daily for 16 days. Femoral areal bone mineral density (aBMD, by DEXA) was decreased in GHS+LD and GHS+HD relative to GHS+veh, while there was no effect on SD. Vertebral aBMD was lower in GHS compared to SD and further decreased in GHS+HD. Both femoral and L6 vertebral volumetric BMD (by µCT) were lower in GHS and further reduced by HD. Histomorphometry indicated a decreased osteoclast number in GHS+HD compared to GHS+veh or SD+HD. In tibiae, GHS+HD trabecular thickness and number increased, with a 12-fold increase in osteoid volume but only a threefold increase in bone volume. Bone formation rate was decreased in GHS+HD relative to GHS+veh, confirming the mineralization defect. The loss of BMD and the mineralization defect in GHS rats contribute to increased hypercalciuria; if these effects persist, they would result in decreased bone strength, making these bones more fracture-prone. The enhanced effect of 1,25D in GHS rats indicates that the increased VDRs are biologically active.

The effect of a diet containing 70% protein from plants on mineral metabolism and musculoskeletal health in chronic kidney disease.

BACKGROUND: Chronic Kidney Disease (CKD) is associated with alterations in phosphorus excretion, and increases in fibroblast growth factor (FGF23) and parathyroid hormone (PTH). Plant protein-based phytate-bound phosphorus, is less bioavailable than that from animal sources. Our one-week study that was conducted previously showed that a nearly 100% plant protein-based diet benefits mineral metabolism in CKD; however, this diet may not be acceptable to patients. Here we hypothesize that a diet containing 70% protein from plants has similar efficacy and is tolerated by CKD patients. METHODS: Thirteen subjects with CKD 3-4 received an omnivorous diet containing 70% protein from plants for 4 weeks. The primary outcome was change in 24 h urine phosphorus. Secondary outcomes were changes in serum phosphorus, FGF23, PTH, urine sodium excretion, grip strength and fat free mass. Repeated measures analysis of variance (ANOVA) was used to test differences in parameters over the 4 weeks. RESULTS: Mean age of subjects was 54.8 years. Median eGFR was 26 (IQR 14.7) ml/min/1.73 m(2). Over the 4-week period, urine phosphorus significantly decreased by 215 ± 232 mg/day (p < 0.001). No significant changes in serum FGF23, phosphorus or PTH were noted. Urine sodium and titratable acid decreased significantly on the diet. Hand grip strength and fat-free mass did not change. There were two hyperkalemia events both 5.8 mEq/l, corrected by food substitutions. No other adverse events were observed. CONCLUSIONS: A 70% plant protein diet is safe, tolerated, and efficacious in lowering urine phosphorus excretion and may be an alternative to phosphate binders.

Weight, age and coefficients of variation in renal solute excretion.

BACKGROUND: Homoscedasticity (constant variance over axes or among statistical factors) is an integral assumption of most statistical analyses. However, a number of empirical studies in model organisms and humans demonstrate significant differences in residual variance (that component of phenotype unexplained by known factors) or intra-individual variation among genotypes. Our work suggests that renal traits may be particularly susceptible to randomization by genetic and non-genetic factors, including endogenous variables like age and weight. METHODS: We tested associations between age, weight and intra-individual variation in urinary calcium, citrate, chloride, creatinine, potassium, magnesium, sodium, ammonium, oxalate, phosphorus, sulfate, uric acid and urea nitrogen in 9,024 male and 6,758 female kidney stone patients. Coefficients of variation (CVs) were calculated for each individual for each solute from paired 24-hour urines. Analysis of CVs was corrected for inter-measurement collection variance in creatinine and urine volume. CVs for sodium and urea nitrogen were included to correct for dietary salt and protein. RESULTS: Age was positively associated with individual CVs for calcium and negatively associated with CVs for potassium, ammonium and phosphorus (p(FDR) < 0.01). Weight was associated with CVs for creatinine, magnesium and uric acid, and negatively associated with CVs for calcium, potassium and oxalate (p(FDR) < 0.05). CONCLUSION: Intra-individual variation changes over age and weight axes for numerous urinary solutes. Changing residual variance over age and weight could cause bias in the detection or estimation of genetic or environmental effects. New methodologies may need to account for such residual unpredictability, especially in diverse collections.

Splenda® improves tolerance of oral potassium citrate supplementation for prevention of stone formation: results of a randomized double-blind trial.

BACKGROUND AND PURPOSE: Oral citrate supplements have been shown to decrease kidney stone recurrence rates in both laboratory and clinical studies. The taste of the citrate supplements, however, is poor, and long-term compliance is low. Our objective was to determine if Splenda(®) added to potassium citrate (KCit) improves palatability without changing 24-hour urine parameters. PATIENTS AND METHODS: 12 subjects were randomly assigned to receive either KCit alone for 3 days or KCit + Splenda in a double-blind trial. The 24-hour urine collections were performed before and after 3 days of therapy. After 1 week, the two groups switched treatments. After each treatment, a visual analog taste scale was completed to gauge the taste and palatability. The 24-hour urine parameters of kidney stone risk factors were compared between groups. The primary end points were to determine whether Splenda improved palatability of citrate supplementation and whether it altered 24-hour urine parameters. RESULTS: Taste was judged to be 2.5 ± 0.9 points better in the Splenda + KCit compared with KCit alone (P=0.02). The 24-hour Cit, K, and pH were significantly higher in the KCit and KCit + Splenda groups compared with baseline, but not significantly different from each other. CONCLUSION: Splenda significantly improves the palatability of KCit therapy and does not alter the beneficial effects of KCit on 24-hour urine Cit, K, or pH. The addition of Splenda altered the average taste score from one that might prohibit compliance to one that would not.

Citrate, malate and alkali content in commonly consumed diet sodas: implications for nephrolithiasis treatment.

PURPOSE: Citrate is a known inhibitor of calcium stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic calcium or uric acid nephrolithiasis. MATERIALS AND METHODS: Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient. RESULTS: Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis (6.30 mEq/l citrate as alkali and 6.30 as total alkali). These sodas were Diet Sunkist Orange, Diet 7Up, Sprite Zero, Diet Canada Dry Ginger Ale, Sierra Mist Free, Diet Orange Crush, Fresca and Diet Mountain Dew. Colas, including Caffeine Free Diet Coke, Coke Zero, Caffeine Free Diet Pepsi and Diet Coke with Lime, had the lowest total alkali (less than 1.0 mEq/l). There was no significant correlation between beverage pH and total alkali content. CONCLUSIONS: Several commonly consumed diet sodas contain moderate amounts of citrate as alkali and total alkali. This information is helpful for dietary recommendations in patients with calcium nephrolithiasis, specifically those with hypocitraturia. It may also be useful in patients with low urine pH and uric acid stones. Beverage malate content is also important since malate ingestion increases the total alkali delivered, which in turn augments citraturia and increases urine pH.

Intestinal and renal effects of low-volume phosphate and sulfate cathartic solutions designed for cleansing the colon: pathophysiological studies in five normal subjects.

OBJECTIVES: Ingestion of a concentrated low-volume phosphate solution produces copious diarrhea, which cleanses the colon, but it occasionally causes renal failure due to calcium phosphate precipitation in renal tubules. We hypothesized that a concentrated low-volume sulfate solution would be an equally effective cathartic, and that urine produced after sulfate would have less tendency to precipitate calcium salts than urine produced after phosphate. METHODS: Hydrated subjects ingested 75 ml of phosphosoda or an equimolar dose of sulfate salts in a small volume of solution. Four liters of PEG (polyethylene glycol) lavage solution was the control. All solutions were administered in split doses, 10 h apart. Propensity of urine to precipitate at pH 6.4 (the pH of renal tubular fluid) was assessed by determining the minimal calcium concentration that caused precipitation. RESULTS: Average diarrheal stool weight was 2,004 g after phosphate, 2,854 g after sulfate, and 3,021 g after PEG (P<0.001). Average calcium concentration (in mg/dl) required to induce urine precipitation at pH 6.4 was 43 after PEG, 10 after PO(4), and 187 after SO(4) (P=0.009). CONCLUSIONS: (i) In equimolar doses, sulfate produced 42% more diarrheal stool weight than phosphate. (ii) Phosphate increased the propensity for calcium salt precipitation in urine at pH 6.4, whereas sulfate did not. (iii) These results suggest that a hypertonic low-volume sulfate solution would be an effective cathartic for colon cleansing and that sulfate-induced catharsis would be less likely than phosphate catharsis to produce calcium salt deposition in renal tubules.

A randomized, controlled trial of lactic acid bacteria for idiopathic hyperoxaluria.

BACKGROUND: Urinary oxalate excretion is an important contributor to calcium oxalate stone formation. Methods of reducing oxalate excretion are not wholly satisfactory, and no controlled trials using them have been performed to prevent stone recurrence. Some lactic acid bacteria can degrade oxalate in vitro. This study sought to reduce urinary oxalate excretion in calcium stone formers with idiopathic hyperoxaluria. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A randomized, double-blind, placebo-controlled trial was performed of Oxadrop, a mix of four lactic acid bacterium species. This preparation previously reduced oxalate excretion in stone formers with idiopathic and enteric hyperoxaluria. Patients were selected from two stone prevention clinics. Twenty people with calcium stones and idiopathic hyperoxaluria (>40 mg/d) were enrolled and randomly assigned 1:1 in placebo and active preparation arms. Both groups took 3.6 g of granulate each day: Either placebo or the experimental preparation. Participants performed two consecutive 24-h urine collections at baseline, at 28 d of therapy, and at 56 d, after being off the preparation for 4 wk. Diet was replicated at each point. RESULTS: There was no effect of the study preparation: Mean 24-h urinary oxalate excretion in placebo-treated patients was 73.9 mg at baseline and 72.7 mg after treatment, whereas the Oxadrop-treated patients had 59.1 mg at baseline and 55.4 mg after treatment. The preparation was well tolerated; three participants on active treatment experienced mild constipation. CONCLUSIONS: In this randomized, placebo-controlled trial, Oxadrop did not reduce urinary oxalate excretion in participants with idiopathic hyperoxaluria.

Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats.

Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone-forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-l-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation.