Calcium Oxalate Supersaturation Research Articles

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

BackgroundObservational studies in obese adults have found abnormal urinary metabolic indices that predispose to nephrolithiasis. Few studies have been performed in severely obese adolescents. ObjectivesTo assess urinary stone risk factors in severely obese adolescents and in those undergoing 2 types of weight loss surgery. SettingChildren’s hospital, United States. MethodsA 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. ResultsA 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. ConclusionsElevated 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.

Efficacy of Mixtures of Magnesium, Citrate and Phytate as Calcium Oxalate Crystallization Inhibitors in Urine

The main aim of the current study was to evaluate the effectiveness of mixtures of magnesium, citrate and phytate as calcium oxalate crystallization inhibitors. A turbidimetric assay in synthetic urine was performed to obtain induction times for calcium oxalate crystallization in the absence and presence of different mixtures of inhibitors. The morphology of calcium oxalate crystals in the absence or presence of inhibitors and mixtures of the inhibitors was evaluated in 2 crystallization experiments at low and high calcium oxalate supersaturation. The crystals formed were examined using scanning electron microscopy. Examination of crystallization induction times revealed clear inhibitory effects of magnesium, citrate and phytate on calcium oxalate crystallization, supporting usefulness in the treatment and prevention of calcium oxalate nephrolithiasis. Significant synergistic effects between magnesium and phytate were observed. Scanning electron microscopy images revealed that phytate is a powerful crystal growth inhibitor of calcium oxalate, totally preventing the formation of trihydrate and monohydrate. In addition to crystallization inhibition capacity, citrate and magnesium avoided calcium oxalate crystallization by decreasing its supersaturation. The synergistic effect between magnesium and phytate on calcium oxalate crystallization suggests that a combination of these 2 compounds may be highly useful as antilithiasis therapy.

Does Hypertension Impact 24-Hour Urine Parameters in Patients With Nephrolithiasis?

To examine the differences in 24-hour urine parameters and stone composition between patients with and without systemic hypertension (HTN) in a large cohort of stone formers. We performed a retrospective review over a 10-year period of patients with stone, who had completed a 24-hour urinalysis (Litholink) and for whom demographic information was available, including the presence of HTN. Univariate and multivariate analyses were performed, comparing the 24-hour urinalysis profiles of patients with HTN with that of normotensive patients. Of the 1115 patients eligible for inclusion, 442 patients (40%) had HTN and 673 (60%) did not. Patients with HTN were significantly older, had a higher body mass index, and had a greater number of comorbid conditions than normotensive patients. Univariate analysis revealed significantly lower urine pH, calcium, supersaturation (SS) of calcium oxalate (CaOx) and SS calcium phosphate (all P<.05) in patients with HTN. Multivariate analysis showed significantly lower calcium, citrate, and SS CaOx in patients with HTN (all P<.05). Our results demonstrate lower levels of calcium and SS CaOx on univariate and multivariate analysis, as well as lower levels of citrate on multivariate analysis in patients with HTN. These results suggest that lower levels of citrate may contribute to stone formation to a greater degree in patients with HTN than abnormalities in calcium metabolism.

Arginine as a Significant Regulator of Supersaturation in Calcium Oxalate Lithiasis: the Physiological Evidence

Background: At present, the possible effect of arginine as a natural regulator of calcium oxalate (CaOX) supersaturation and crystallization in human urine has been analyzed. Methods: Two types of experiments have been discussed: clinical laboratory analysis on the urine excretion of arginine (Arg) in patients with CaOX lithiasis and detailed measurements of the kinetics of the dissolution of CaOX calculi in artificial urine, containing various concentrations of Arg. Results: A detailed analysis showed that 80% of stone formers (SFs) eliminated pathological values: 30% of patients had lower plasma levels compared to controls and about 50% of SFs showed higher concentration. Urine concentrations in these two groups were not reported. Conclusions: The in vitro analytical measurements demonstrate even a possibility to dissolve CaOX stones in human urine, in which increased concentration of Arg has been established. Discussions have arisen to use increased concentration of Arg in urine both as a solubilizator of CaOX stones in humans and on the purpose of a prolonged metaphylactic treatment. World J Nephrol Urol. 2015;4(1):173-177 doi: http://dx.doi.org/10.14740/wjnu199w

Recurrence of crystalline nephropathy after kidney transplantation in APRT deficiency and primary hyperoxaluria.

Purpose of reviewTo provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT) deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients.Source of informationPubmed literature search.SettingPrimary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism. The hallmark of these diseases is the overproduction and urinary excretion of compounds (2,8 dihydroxyadenine in APRT deficiency, oxalate in primary hyperoxaluria) that form urinary crystals. Although recurrent urolithiasis represents the main clinical feature of these diseases, kidney injury can occur as a result of crystal precipitation within the tubules and interstitium, a condition referred to as crystalline nephropathy. Some patients develop end-stage renal disease (ESRD) and may become candidates for kidney transplantation. Since kidney transplantation does not correct the underlying metabolic defect, transplant recipients have a high risk of recurrence of crystalline nephropathy, which can lead to graft loss. In some instances, the disease remains undiagnosed until after the occurrence of ESRD or even after kidney transplantation.Key messagesPatients with APRT deficiency or primary hyperoxaluria may develop ESRD as a result of crystalline nephropathy. In the absence of diagnosis and adequate management, the disease is likely to recur after kidney transplantation, which often leads to rapid loss of renal allograft function. Primary hyperoxaluria, but not APRT deficiency, becomes a systemic disease at low GFR with oxalate deposition leading to malfunction in non-renal organs (systemic oxalosis). We suggest that these diagnoses should be considered in patients with low glomerular filtration rate (GFR) and a history of kidney stones. In APRT deficiency, stones may be confused with uric acid stones, unless specialized techniques are used (infrared spectroscopy or X-ray crystallography for urinary crystals or stone analysis; Fourier transform infrared microscopy for crystals in kidney biopsy). Where these are unavailable, and for confirmation, the diagnosis can be made by measurement of enzyme activity in red blood cell lysates or by genetic testing. In patients with primary hyperoxaluria, levels of urinary and plasma oxalate; and the presence of nearly pure calcium oxalate monohydrate in stones, which often also have an unusually pale colour and unorganized structure, increase diagnostic suspicion. Molecular genetic testing is the criterion measure. Lifelong allopurinol therapy, with high fluid intake if appropriate, may stabilize kidney function in APRT deficiency; if ESRD has occurred or is near, results with kidney transplantation after initiation of allopurinol are excellent. In primary hyperoxaluria recognized before ESRD, pyridoxine treatment and high fluid intake may lead to a substantial decrease in urinary calcium oxalate supersaturation and prevent renal failure. In non-responsive patients or those recognized later in their disease, liver transplantation cures the underlying defect and should be considered when the GFR falls below 30 ml/min/1.73 m2; in those which or near ESRD, liver transplantation and intensive dialysis before kidney transplantation may be considered to reduce the total body oxalate burden before kidney transplantation.LimitationsThe availability of diagnostic tests varies between countries and centres. Data on long term outcomes after kidney transplantation are limited, especially for APRT deficiency patients.ImplicationsIncreasing transplant physicians knowledge of APRT deficiency and primary hyperoxaluria should enable them to implement adequate diagnostic and therapeutic interventions, thereby achieving good outcomes after kidney transplantation.

Caffeine intake and the risk of kidney stones

Although caffeine intake may increase urine calcium excretion, caffeine-containing beverages have been associated with a lower risk of nephrolithiasis. We sought to determine the association between caffeine intake and the risk of incident kidney stones in 3 large prospective cohorts. We prospectively analyzed the association between intake of caffeine and incidence of kidney stones in 3 large ongoing cohort studies, the Health Professionals Follow-Up Study (HPFS) and the Nurses' Health Studies (NHS) I and II. Information on the consumption of caffeine and the incidence of kidney stones was collected by validated questionnaires. The analysis included 217,883 participants; over a median follow-up of >8 y, 4982 incident cases occurred. After multivariate adjustment for age, BMI, fluid intake, and other factors, participants in the highest quintile of caffeine intake had a 26% (95% CI: 12%, 38%) lower risk of developing stones in the HPFS cohort, a 29% lower risk (95% CI: 15%, 41%) in the NHS I cohort, and a 31% lower risk (95% CI: 18%, 42%) in the NHS II cohort (P-trend < 0.001 for all cohorts). The association remained significant in the subgroup of participants with a low or no intake of caffeinated coffee in the HPFS cohort. Among 6033 participants with 24-h urine data, the intake of caffeine was associated with higher urine volume, calcium, and potassium and with lower urine oxalate and supersaturation for calcium oxalate and uric acid. Caffeine intake is independently associated with a lower risk of incident kidney stones.

Differences in 24-h urine composition between nephrolithiasis patients with and without diabetes mellitus.

To examine the differences in 24-h urine composition between nephrolithiasis patients with and without diabetes mellitus (DM) in a large cohort of stone-formers and to examine differences in stone composition between patients with and without DM. A retrospective review of 1117 patients with nephrolithiasis and a 24-h urine analysis was completed. Univariable analysis of 24-h urine profiles and multivariable linear regression models were performed, comparing patients with and without DM. A subanalysis of patients with stone analysis data available was performed, comparing the stone composition of patients with and without DM. Of the 1117 patients who comprised the study population, 181 (16%) had DM and 936 (84%) did not have DM at the time of urine analysis. Univariable analysis showed significantly higher total urine volume, citrate, uric acid (UA), sodium, potassium, sulphate, oxalate, chloride, and supersaturation (SS) of UA in individuals with DM (all P < 0.05). However, patients with DM had significantly lower SS of calcium phosphate and pH (all P < 0.05). Multivariable analysis showed that patients with DM had significantly lower urinary pH and SS of calcium phosphate, but significantly greater citrate, UA, sulphate, oxalate, chloride, SSUA, SS of calcium oxalate, and volume than patients without DM (all P < 0.05). Patients with DM had a significantly greater proportion of UA in their stones than patients without DM (50.2% vs 13.5%, P < 0.001). DM was associated with multiple differences on 24-h urine analysis compared with those without DM, including significantly higher UA and oxalate, and lower pH. Control of urinary UA and pH, as well as limiting intake of dietary oxalate may reduce stone formation in patients with DM.

Sulfate but not thiosulfate reduces calculated and measured urinary ionized calcium and supersaturation: implications for the treatment of calcium renal stones.

BackgroundUrinary sulfate (SO4 2−) and thiosulfate (S2O3 2−) can potentially bind with calcium and decrease kidney stone risk. We modeled the effects of these species on the concentration of ionized calcium (iCa) and on supersaturation (SS) of calcium oxalate (CaOx) and calcium phosphate (CaP), and measured their in vitro effects on iCa and the upper limit of stability (ULM) of these salts.MethodsUrine data from 4 different types of stone patients were obtained from the Mayo Nephrology Clinic (Model 1). A second data set was obtained from healthy controls and hypercalciuric stone formers in the literature who had been treated with sodium thiosulfate (STS) (Model 2). The Joint Expert Speciation System (JESS) was used to calculate iCa and SS. In Model 1, these parameters were calculated as a function of sulfate and thiosulfate concentrations. In Model 2, data from pre- and post STS urines were analyzed. ULM and iCa were determined in human urine as a function of sulfate and thiosulfate concentrations.ResultsCalculated iCa and SS values for all calcium salts decreased with increasing sulfate concentration. Thiosulfate had no effect on these parameters. In Model 2, calculated iCa and CaOx SS increased after STS treatment, but CaP SS decreased, perhaps due to a decrease in pH after STS treatment. In confirmatory in vitro experiments supplemental sulfate, but not thiosulfate, significantly increased the calcium needed to achieve the ULM of CaP and tended to increase the oxalate needed to reach the ULM of CaOx. Sulfate also significantly decreased iCa in human urine, while thiosulfate had no effect.ConclusionIncreasing urinary sulfate could theoretically reduce CaOx and CaP stone risk. Although STS may reduce CaP stone risk by decreasing urinary pH, it might also paradoxically increase iCa and CaOx SS. As such, STS may not be a viable treatment option for stone disease.

Enteric hyperoxaluria secondary to small bowel resection: use of computer simulation to characterize urinary risk factors for stone formation and assess potential treatment protocols.

We used computer modeling to investigate the influence of physicochemical stone risk factors on urinary supersaturation (SS) of calcium oxalate (CaOx) in patients with severe hyperoxaluria, relative hypocalciuria, hypocitraturia, and CaOx nephrolithiasis after extensive small bowel resection, usually performed for Crohn's disease. We also simulated different treatment strategies, including oral calcium supplements and citrate, in such patients. A baseline urine model was derived by consolidating data acquired by ourselves with those from another patient cohort. Calcium and oxalate excretions in this model were altered to obtain an extreme case. For comparison, additional models were based on published urine data from normal subjects (N) and idiopathic CaOx stone formers (SF). The Joint Expert Speciation System was used to simulate different urine situations based on reported compositional values. [Ca(2+)][Ox(2-)] ionic concentration products and SS(CaOx) are substantially higher in enteric hyperoxaluric patients than in N and SF, despite their relatively lower calcium excretions. Molar Ca:Ox ratios are substantially lower in enteric hyperoxalurics than in N and SF. Oral calcium supplements can reduce SS(CaOx), but monitoring is required to avoid exceeding a safe dosing threshold. A simple calculation can alert the clinician that this threshold is being approached or even exceeded. Increasing urinary pH and citrate decreases SS(CaOx) but not to the same extent as decreasing Ox excretion. Calcium supplements can help reduce stone risk in patients with severe enteric hyperoxaluria, but initial efforts should be directed toward reducing urinary oxalate by reducing dietary oxalate. Citrate therapy that increases both urine pH and urinary citrate provides an additional therapeutic benefit.

Age-Related Changes in 24-Hour Urine Composition Must be Considered in the Medical Management of Nephrolithiasis

Over the past 50 years, there has been an upward shift in the age of peak incidence of stone disease, yet less is known regarding how the urinary biochemical profile changes with aging. Therefore, we sought to examine the relationship between age and 24-hour urine composition. We retrospectively reviewed a database of our tertiary care stone clinic patients seen from March 2002 to February 2012. Analysis of pretreatment 24-hour urine collections across age groups was performed using univariate analysis of variance and multivariate linear regression models adjusting for clinical and demographic factors and 24-hour urine parameters. A total of 1115 patients were broken down into age groups consisting of <45 years (221; 19.7%), 45-54.9 years (270; 23.8%), 55-64.9 years (270; 24.6%), and ≥65 years (356; 31.9%). Univariate analysis found significant ascending trends with aging for mean body mass index, while mean urine pH, 24-hour calcium, uric acid (UA), ammonium, creatinine, and supersaturation (SS) of calcium oxalate (CaOx) and calcium phosphate (CaP) decreased with age (all P for trend <0.05). Adjusted multivariate analysis demonstrated that increased age was significantly associated with increased 24-hour citrate and SS UA, whereas increased age was significantly associated with decreased pH, 24-hour UA, creatinine, SS CaOx, and SS CaP (all P for trend <0.05). There are numerous age-related changes in the metabolic profile as seen on 24-hour urine collection. This highlights the importance of evaluating stone-forming patients of all ages with 24-hour urine collections because both the type and degree of metabolic abnormality may change with age.

Urinary Lithogenic Risk Profile in Recurrent Stone Formers With Hyperoxaluria: A Randomized Controlled Trial Comparing DASH (Dietary Approaches to Stop Hypertension)-Style and Low-Oxalate Diets

Patients with nephrolithiasis and hyperoxaluria generally are advised to follow a low-oxalate diet. However, most people do not eat isolated nutrients, but meals consisting of a variety of foods with complex combinations of nutrients. A more rational approach to nephrolithiasis prevention would be to base dietary advice on the cumulative effects of foods and different dietary patterns rather than single nutrients. Randomized controlled trial. Recurrent stone formers with hyperoxaluria (urine oxalate > 40 mg/d). The intervention group was asked to follow a calorie-controlled Dietary Approaches to Stop Hypertension (DASH)-style diet (a diet high in fruit, vegetables, whole grains, and low-fat dairy products and low in saturated fat, total fat, cholesterol, refined grains, sweets, and meat), whereas the control group was prescribed a low-oxalate diet. Study length was 8 weeks. Primary: change in urinary calcium oxalate supersaturation. Changes in 24-hour urinary composition. 57 participants were randomly assigned (DASH group, 29; low-oxalate group, 28). 41 participants completed the trial (DASH group, 21; low-oxalate group, 20). As-treated analysis showed a trend for urinary oxalate excretion to increase in the DASH versus the low-oxalate group (point estimate of difference, 9.0mg/d; 95% CI, -1.1 to 19.1mg/d; P=0.08). However, there was a trend for calcium oxalate supersaturation to decrease in the DASH versus the low-oxalate group (point estimate of difference, -1.24; 95% CI, -2.80 to 0.32; P=0.08) in association with an increase in magnesium and citrate excretion and urine pH in the DASH versus low-oxalate group. Limited sample size, as-treated analysis, nonsignificant results. The DASH diet might be an effective alternative to the low-oxalate diet in reducing calcium oxalate supersaturation and should be studied more.

A test of the hypothesis that oxalate secretion produces proximal tubule crystallization in primary hyperoxaluria type I

The sequence of events by which primary hyperoxaluria type 1 (PH1) causes renal failure is unclear. We hypothesize that proximal tubule (PT) is vulnerable because oxalate secretion raises calcium oxalate (CaOx) supersaturation (SS) there, leading to crystal formation and cellular injury. We studied cortical and papillary biopsies from two PH1 patients with preserved renal function, and seven native kidneys removed from four patients at the time of transplant, after short-term (2) or longer term (2) dialysis. In these patients, and another five PH1 patients without renal failure, we calculated oxalate secretion, and estimated PT CaOx SS. Plasma oxalate was elevated in all PH1 patients and inverse to creatinine clearance. Renal secretion of oxalate was present in all PH1 but rare in controls. PT CaOx SS was >1 in all nonpyridoxine-responsive PH1 before transplant and most marked in patients who developed end stage renal disease (ESRD). PT from PH1 with preserved renal function had birefringent crystals, confirming the presence of CaOx SS, but had no evidence of cortical inflammation or scarring by histopathology or hyaluronan staining. PH1 with short ESRD showed CaOx deposition and hyaluronan staining particularly at the corticomedullary junction in distal PT while cortical collecting ducts were spared. Longer ESRD showed widespread cortical CaOx, and in both groups papillary tissue had marked intratubular CaOx deposits and fibrosis. CaOx SS in PT causes CaOx crystal formation, and CaOx deposition in distal PT appears to be associated with ESRD. Minimizing PT CaOx SS may be important for preserving renal function in PH1.

Influence of the lysine on the calcium oxalate renal calculi

Plasma levels and urinary excretions of amino acid lysine were estimated by high-performance liquid chromatography in 15 control subjects and 56 stone formers (SFs) with calcium oxalate (CaOX) urolithiasis. Data demonstrated clearly that there is a general tendency toward decreased lysine's excretions in above 40% of SFs. Moreover, it was found that DL-lysine, a normal physiological constituent of urine, acts at increased concentrations as a dissolving agent with respect to CaOX and CaOX calculi. The kinetics of dissolution of crystalline calcium oxalate calculi in physiological solutions containing DL-lysine at different concentrations is studied, using the change in the Archimedean weight of samples immersed in the solution. The possible effect of lysine as a natural regulator of CaOX supersaturation and crystallization in human urine is also discussed.

Dietary Management of Idiopathic Hyperoxaluria and the Influence of Patient Characteristics and Compliance

To assess the efficacy of dietary management for the treatment of idiopathic hyperoxaluria in a large tertiary care center and examine the influence of patient factors, compliance, and follow-up on oxalate reduction, which has not been previously investigated. Retrospectively, 149 patients with kidney stones with idiopathic hyperoxaluria who received dietary management at our stone clinic were evaluated. Changes in urinary parameters on 24-hour urine collections were calculated for all patients and those with abnormal values in the overall short-term (30-240 days) and long-term (>240 days) time periods. Changes in urinary oxalate were evaluated with respect to patient characteristics and compliance measures. Urine oxalate and supersaturation of calcium oxalate were significantly (P < .001) reduced by 8.9 ± 19.2 mg/d and 1.7 ± 4.3, respectively. A total of 48.3% of the patients reduced their urinary oxalate to normal. Urine oxalate reductions were similar in the short-term and long-term periods. Women lowered urine oxalate nearly twice as much as men (12.7 ± 2.0 mg/d vs 6.7 ± 2.2 mg/d, P = .022) and body mass index (BMI) negatively correlated with oxalate reduction (Pearson's r = -0.213). Reported noncompliance and keeping follow-up appointments did not affect oxalate, however, there was a significant correlation between increasing urine volume and reducing oxalate (Pearson's r = -0.21). This study confirms that meaningful reductions of urine oxalate and supersaturation of calcium oxalate can be achieved with dietary management of hyperoxaluria on a larger clinical scale. Furthermore, we identified that women and patients with low BMIs had greater urine oxalate reductions and urine volume may also be used by clinicians as a measure of dietary compliance.

Calcium oxalate supersaturation increases early after Roux-en-Y gastric bypass

BackgroundCalcium oxalate (CaOx) nephrolithiasis is an adverse effect of Roux-en-Y gastric bypass surgery (RYGB). It is unknown when the increased risk for CaOx stone formation occurs after surgery. MethodsWe studied 13 morbidly obese adults undergoing RYGB with 24-hour urine collections at 4 weeks before and 1, 2, 4, and 6 months after surgery and computed CaOx relative saturation ratio (RSR) by EQUIL2. ResultsEleven patients were female, mean±standard deviation age was 41.1±7.2 years, and none had diabetes or chronic kidney disease. Median (interquartile range) urinary oxalate excretion increased linearly from 12.6 (10.9–37.9) mg/24 hr at baseline to 28.4 (14.4–44.0) mg/24 hr at 6 months (slope = .188; P = .005). CaOx RSR increased significantly at 2 months after RYGB (1.4 [1.2–2.4] to 4.9 [1.7–10.0]; P = .017) and rose throughout the study to 5.7 (3.7–12.2) at 6 months (P = .001) with a positive linear slope (.255; P = .001). One patient had critical CaOx supersaturation (RSR = 34.7) and severe hyperoxaluria (101.7 mg/24 hr) at 6 months after RYGB. Significant decreases over time were seen in urine volume and sodium and potassium excretion, but no changes were noted in urinary pH, calcium, magnesium, or citrate. ConclusionsOur data suggest that CaOx RSR, and thus risk for nephrolithiasis, rises as early as 2 months after RYGB and increases gradually in the first 6 months, largely because of reduced urine volume and increased urinary oxalate excretion. Interventions to reduce CaOx RSR, such as adequate fluid intake and agents to bind enteric oxalate, need to be evaluated in patients at risk for nephrolithiasis after RYGB.

The Effect of Sodium Bicarbonate Upon Urinary Citrate Excretion in Calcium Stone Formers

To evaluate the effects of oral sodium bicarbonate (NaBic) supplementation upon urinary citrate excretion in calcium stone formers (CSFs). Sixteen adult calcium stone formers with hypocitraturia were enrolled in a randomized, double-blind, crossover protocol using 60 mEq/day of NaBic during 3 days compared to the same period and doses of potassium citrate (KCit) supplementation. Blood and 24-hour urine samples were collected at baseline and during the third day of each alkali salt. NaBic, similarly to KCit supplementation, led to an equivalent and significant increase in urinary citrate and pH. Compared to baseline, NaBic led to a significant increase in sodium excretion without concomitant increases in urinary calcium excretion, whereas KCit induced a significant increase in potassium excretion coupled with a significant reduction in urinary calcium. Although NaBic and KCit both reduced calcium oxalate supersaturation (CaOxSS) significantly vs baseline, KCit reduced calcium oxalate supersaturation significantly further vs NaBic. Both KCit and NaBic significantly reduced urinary phosphate and increased calcium phosphate supersaturation (CaPSS) compared to baseline. Finally, a significantly higher sodium urate supersaturation (NaUrSS) was observed after the use of the 2 drugs. This short-term study suggests that NaBic represents an effective alternative for the treatment of hypocitraturic calcium oxalate stone formers who cannot tolerate or afford the cost of KCit. In view of the increased sodium urate supersaturation, patients with pure uric acid stones and high urate excretion may be less suited for treatment with NaBic.

A Pilot Study of the Effect of Sodium Thiosulfate on Urinary Lithogenicity and Associated Metabolic Acid Load in Non-Stone Formers and Stone Formers with Hypercalciuria

Background and ObjectivesSodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people.Design, Setting, Participants & MeasurementsSTS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry.ResultsSTS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P<0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate.ConclusionsThe basis for studies demonstrating that STS prevented stones in rats and people was not reflected by the changes in urine chemistry reported here. Although serum HCO3 did not change, urine tests suggested an acid load in both non-stone forming and hypercalciuric stone-forming participants. The long term safety of STS needs to be determined before the drug can be tested in humans for long-term prevention of stone recurrence.

Is there a better way to work-up kidney stones?

Nephrolithiasis represents a significant burden of illness for Canadians. It has a lifetime risk of 10%–15% and a recurrence risk of up to 50% within 5–10 years and up to 75% at 20 years.1 While most stones pass spontaneously, the direct and indirect costs of managing stones in the United States was estimated to be in excess of US$5.3 billion in 2000.2 Although shock wave lithotripsy and endourologic procedures have revolutionized surgical stone therapy and allow the vast majority of stones to be treated in a minimally invasive fashion, most patients would prefer stone prevention to stone recurrence. The question then becomes that of determining the optimal method for diagnosing the etiology of stone formation in particular patients so that a coherent and evidence-based prevention strategy encompassing dietary recommendations and medical therapy can be implemented. The current gold standard for assessing stone formation risk includes multiple 24-hour urine assessments carried out along with serum electrolyte measurements. Rossi and colleagues3 present data comparing centralized laboratory assessments of calcium oxalate and calcium phosphate supersaturation with 24-hour urine assessments of concentrations. The authors demonstrate that in 150 stone formers 24-hour urine concentration values tend to overestimate the number of patients at risk for supersaturation (i.e., 24-hour urine concentrations have a high false-positive rate or lower specificity). They suggest that measurement of urinary supersaturation might prevent overtreatment of patients at risk for stone recurrence. It is premature, however, to recommend replacing 24-hour urine collection with centralized urinary supersaturation assessments. The patients in the current study were known stone formers and were undergoing treatment at the time of study, and so they may not be representative of de novo stone formers or of patients not on stone-prevention therapy. In addition, although it is theoretically appealing, there are no prospective data available to suggest that patients followed with serial urinary supersaturation (rather than 24-hour urine collections) have lower risk for stone recurrence or more favourable clinical outcomes, nor are there data to suggest that altering urinary supersaturation alters the natural history of stone formation. Further, a formal cost–benefit analysis of centralized urinary supersaturation versus 24-hour urine collection is needed to assess the trade-offs between a more costly test (the former) and a test with potentially more false-positive results (the latter). Finally, it is not surprising that the measured supersaturation of calcium oxalate and calcium phosphate will be lower than supersaturation levels calculated from 24-hour collection data because the latter data do not account for ionic stabilizers and stone inhibitors such as citrate. Perhaps modification to Equil 2 calculations to incorporate citrate concentration might lead to a more accurate estimation of supersaturation from 24-hour urine values. More work is clearly needed before it is recommended that physicians replace the venerable 24-hour urine collection (imperfect and limited though it is) in the medical evaluation of recurrent stone formers.

Dietary hyperoxaluria is not reduced by treatment with lactic acid bacteria

BackgroundSecondary hyperoxaluria either based on increased intestinal absorption of oxalate (enteric), or high oxalate intake (dietary), is a major risk factor of calcium oxalate urolithiasis. Oxalate-degrading bacteria might have beneficial effects on urinary oxalate excretion resulting from decreased intestinal oxalate concentration and absorption.MethodsTwenty healthy subjects were studied initially while consuming a diet normal in oxalate. Study participants were then placed on a controlled oxalate-rich diet for a period of 6 weeks. Starting with week 2 of the oxalate-rich diet, participants received 2.6 g/day of a lactic acid bacteria preparation for 5 weeks. Finally, subjects were examined 4 weeks after treatment while consuming again a normal-oxalate diet. Participants provided weekly 24-hour urine specimens. Analyses of blood samples were performed before and at the end of treatment.ResultsUrinary oxalate excretion increased significantly from 0.354 ± 0.097 at baseline to 0.542 ± 0.163 mmol/24 h under the oxalate-rich diet and remained elevated until the end of treatment, as did relative supersaturation of calcium oxalate. Plasma oxalate concentration was significantly higher after 5 weeks of treatment compared to baseline. Four weeks after treatment, urinary oxalate excretion and relative supersaturation of calcium oxalate fell to reach initial values.ConclusionsPersistent dietary hyperoxaluria and increased plasma oxalate concentration can already be induced in healthy subjects without disorders of oxalate metabolism. The study preparation neither reduced urinary oxalate excretion nor plasma oxalate concentration. The preparation may be altered to select for lactic acid bacteria strains with the highest oxalate-degrading activity.

Hippuric acid as a significant regulator of supersaturation in calcium oxalate lithiasis: the physiological evidence.

At present, the clinical significance of existing physicochemical and biological evidence and especially the results we have obtained from our previous in vitro experiments have been analyzed, and we have come to the conclusion that hippuric acid (C6H5CONHCH2COOH) is a very active solvent of Calcium Oxalate (CaOX) in physiological solutions. Two types of experiments have been discussed: clinical laboratory analysis on the urine excretion of hippuric acid (HA) in patients with CaOX lithiasis and detailed measurements of the kinetics of the dissolution of CaOX calculi in artificial urine, containing various concentrations of HA. It turns out that the most probable value of the HA concentration in the control group is approximately ten times higher than the corresponding value in the group of the stone-formers. Our in vitro analytical measurements demonstrate even a possibility to dissolve CaOX stones in human urine, in which increased concentration of HA have been established. A conclusion can be that drowning out HA is a significant regulator of CaOX supersaturation and thus a regulation of CaOX stone formation in human urine. Discussions have arisen to use increased concentration of HA in urine both as a solubilizator of CaOX stones in the urinary tract and on the purpose of a prolonged metaphylactic treatment.