Sulfate but Not Thiosulfate Reduces Calculated and Measured Urinary Ionized Calcium and Supersaturation: Implications for the Treatment of Calcium Renal Stones

Abstract

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.

The elementome of calcium-based urinary stones and its role in urolithiasis

“…33 For this reason, other investigators have argued that therapeutically increasing urinary sulphate concentrations could actually reduce the risk of calcium-based stones. 34 …”

Sulfate and thiosulfate inhibit oxalate transport via a dPrestin (Slc26a6)-dependent mechanism in an insect model of calcium oxalate nephrolithiasis

“…This transport is of particular interest as thiosulfate administration reduced the occurrence of calcium urolithiasis (27), and thiosulfate is used as a treatment for calcium phosphate nephrolithiasis (2) and nephrocalcinosis (1). Rodgers and coworkers (18) reported that sulfate, but not thiosulfate, had a modest effect of reducing urinary ionized calcium concentration, and concomitantly reducing urinary supersaturation of calcium salts, such as CaOx. Thiosulfate unfavorably increased CaOx supersaturation (18).…”

“…Rodgers and coworkers (18) reported that sulfate, but not thiosulfate, had a modest effect of reducing urinary ionized calcium concentration, and concomitantly reducing urinary supersaturation of calcium salts, such as CaOx. Thiosulfate unfavorably increased CaOx supersaturation (18). This study also concluded that the unfavorable increase in CaOx supersaturation was due to decrements in urine pH following thiosulfate ingestion, rather than urinary thiosulfate concentrations.…”

“…Asplin and colleagues (2) reported that thiosulfate administration significantly reduced spontaneous calcium phosphate stone formation in genetic hypercalciuric stone (GHS)-forming rats (2). More recently, Rodgers and coworkers (18) reported that sulfate but not thiosulfate decreased calculated urinary, ionized Ca 2ϩ and supersaturation in vitro and in silico. Given this information, it can be concluded that evidence for the use of sulfate and thiosulfate in humans and rat models of nephrolithiasis has a positive effectiveness correlation, but that the predicted mechanism of action does not match the experimental outcomes, i.e., decreases in urine ionized calcium.…”

Effect of L-Methionine on the Risk of Phosphate Stone Formation

“…Urinary sulfate is a divalent anion and can potentially bind with ionized calcium in urine, thereby decreasing its availability for complexation with free oxalate and phosphate and concomitantly decreasing the supersaturation of calcium oxalate and calcium phosphate. 17 The generation of protons after the single-dose administration of 1500 mg L-methionine resulted in a significant reduction in urinary pH to values of 6.0-6.2 over a 6-hour period. Acidification between 6.0 and 6.3 was maintained for 24 hours in these subjects on the test day as compared with the control day.…”