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

BACKGROUND: Urinary sulfate (SO 4 2− ) and thiosulfate (S 2 O 3 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. METHODS: Urine 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. RESULTS: Calculated 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. CONCLUSION: Increasing 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

Citrate salts for preventing and treating calcium containing kidney stones in adults

Background: kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate levels. These people have a higher incidence of calcium phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary citrate levels, which in turn binds with calcium and inhibits the crystallisation thus reduces stone formation. Despite the widespread use of oral citrate therapy for prevention and treatment of calcium oxalate stones, the evidence to support its clinical efficacy remains uncertain.Objectives: the objective of this review was to determine the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones.Search methods: we searched the Cochrane Kidney and Transplant Specialised Register to 29 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.Selection criteria: we included randomised controlled trials (RCTs) that assessed the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones in adults treated for a minimum of six months.Data collection and analysis: two authors assessed studies for inclusion in this review. Data were extracted according to predetermined criteria. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes.Main results: we included seven studies that included a total of 477 participants, most of whom had oxalate stones. Of these, three studies (247 participants) compared potassium citrate with placebo or no intervention; three (166 participants) compared potassium-sodium citrate with no intervention; and one (64 participants) compared potassium-magnesium citrate with placebo. Overall, quality of the reporting of the included studies was considered moderate to poor, and there was a high risk of attrition bias in two studies.Compared with placebo or no intervention, citrate therapy significantly reduced the stone size (4 studies, 160 participants: RR 2.35, 95% CI 1.36 to 4.05). New stone formation was significantly lower with citrate therapy compared to control (7 studies, 324 participants: RR 0.26, 95% CI 0.10 to 0.68). The beneficial effect on stone size stability was also evident (4 studies, 160 participants: RR 1.97, 95% CI 1.19 to 3.26). Adverse events were reported in four studies, with the main side effects being upper gastrointestinal disturbance and one patient reported a rash. There were more gastrointestinal adverse events in the citrate group; however this was not significant (4 studies, 271 participants: RR 2.55, 95% CI 0.71 to 9.16). There were significantly more dropouts due to adverse events with citrate therapy compared to control (4 studies, 271 participants: RR 4.45, 95% CI 1.28 to 15.50). The need for retreatment was significantly less with citrate therapy compared to control (2 studies, 157 participants: RR 0.22, 95% CI 0.06 to 0.89).Author's conclusions: nitrate salts prevent new stone formation and reduce further stone growth in patients with residual stones that predominantly contain oxalate. The quality of reported literature remains moderate to poor; hence a well-designed statistically powered multi-centre RCT is needed in order to answer relevant questions concerning the efficacy of citrate salts.</p

Evening primrose oil supplementation increases citraturia and decreases other urinary risk factors for calcium oxalate urolithiasis

PURPOSE: We investigated the effects of gamma-linolenic acid (an omega-6 polyunsaturated fatty acid) in the form of evening primrose oil on calcium oxalate urinary stone risk factors in 2 ethnic groups. MATERIALS AND METHODS: Eight black and 8 white healthy male subjects ingested 1,000 mg evening primrose oil (Natrodale, Kuils River, South Africa) daily for 20 days while following a free diet. Arachidonic acid content was determined by a dietary questionnaire. On days 0, 10 and 20, and 4 days after protocol 24-hour urine samples were collected. Samples were analyzed using routine assays. RESULTS: Citraturia increased significantly in each group. Urinary oxalate showed a tendency to decrease in black subjects. Calciuria and the Tiselius risk index decreased significantly in each group. Carryover effects were observed. CONCLUSIONS: To our knowledge increased citraturia has not been previously reported for any essential fatty acid. We hypothesize that evening primrose oil inhibits lipogenesis, thereby decreasing citrate consumption. For the decrease in oxaluria we suggest that evening primrose oil alters membrane fatty acid composition, thereby inhibiting the modulation of protein kinases that lead to hyperoxaluria. In regard to decreased calciuria we suggest that evening primrose oil modulates delta-5 and/or delta-6-desaturase, thereby inhibiting the production of arachidonic acid and prostaglandin E2, which influence calciuria. The different response in the 2 groups with respect to oxaluria confirms previously reported differences in sensitivity toward supplemental ingestion. Data suggest that evening primrose oil supplementation should be investigated as a possible conservative treatment for calcium oxalate urolithiasis

“An Unquestionable Expert on Avant-Garde”. For Igor Yevgenyevich Vasilyev’s Birthday

<p>Average urine values from a group of calcium oxalate stone formers were used (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103602#pone-0103602-t001" target="_blank">Table 1</a>), and sulfate varied from baseline (100%) to as low as 10% or as high as 500% of that.</p

Evening primrose oil supplementation increases citraturia and decreases other urinary risk factors for calcium oxalate urolithiasis.

PURPOSE: We investigated the effects of gamma-linolenic acid (an omega-6 polyunsaturated fatty acid) in the form of evening primrose oil on calcium oxalate urinary stone risk factors in 2 ethnic groups. MATERIALS AND METHODS: Eight black and 8 white healthy male subjects ingested 1,000 mg evening primrose oil (Natrodale, Kuils River, South Africa) daily for 20 days while following a free diet. Arachidonic acid content was determined by a dietary questionnaire. On days 0, 10 and 20, and 4 days after protocol 24-hour urine samples were collected. Samples were analyzed using routine assays. RESULTS: Citraturia increased significantly in each group. Urinary oxalate showed a tendency to decrease in black subjects. Calciuria and the Tiselius risk index decreased significantly in each group. Carryover effects were observed. CONCLUSIONS: To our knowledge increased citraturia has not been previously reported for any essential fatty acid. We hypothesize that evening primrose oil inhibits lipogenesis, thereby decreasing citrate consumption. For the decrease in oxaluria we suggest that evening primrose oil alters membrane fatty acid composition, thereby inhibiting the modulation of protein kinases that lead to hyperoxaluria. In regard to decreased calciuria we suggest that evening primrose oil modulates delta-5 and/or delta-6-desaturase, thereby inhibiting the production of arachidonic acid and prostaglandin E2, which influence calciuria. The different response in the 2 groups with respect to oxaluria confirms previously reported differences in sensitivity toward supplemental ingestion. Data suggest that evening primrose oil supplementation should be investigated as a possible conservative treatment for calcium oxalate urolithiasis

Average urine chemistries of stone formers representing 4 different types.

<p>Average urine chemistries of stone formers representing 4 different types.</p

JESS-calculated SS and concentrations of ionized species.

<p>Bru: brushite; CaOx: calcium oxalate; CaP: calcium phosphate; COM: calcium oxalate monohydrate; Cys: cystine; HAP: hydroxyapatite; OCP: octacalcium phosphate; sodium thiosulfate (STS); tCaP: tri-calcium phosphate; UA: uric acid.</p><p>Values were calculated using urinary values of healthy subjects at baseline and after ingestion of sodium thiosulfate <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103602#pone.0103602-Okonkwo1" target="_blank">[11]</a>. SS was also re-calculated holding pH constant with increased STS, and holding STS constant with lower pH.</p

Final oxalate or calcium concentration for achieving the ULM for CaOx and CaP as a function of thiosulfate concentration.

<p>Urinary oxalate or calcium is expressed normalized relative to the baseline concentration in that urine sample. At 0.5% more oxalate (P = 0.23) and 4% less calcium (P = 0.27) was needed to reach ULM. Urine samples from 9 stone formers and 2 controls were studied.</p