Thiosulfate reduces calcium phosphate nephrolithiasis

Abstract

An uncontrolled trial reported that sodium thiosulfate reduces formation of calcium kidney stones in humans, but this has not been established in a controlled human study or animal model. Using the genetic hypercalciuric rat, an animal model of calcium phosphate stone formation, we studied the effect of sodium thiosulfate on urine chemistries and stone formation. We fed genetic hypercalciuric rats normal food with or without sodium thiosulfate for 18 wk and measured urine chemistries, supersaturation, and the upper limit of metastability of urine. Eleven of 12 untreated rats formed stones compared with only three of 12 thiosulfate-treated rats (P < 0.002). Urine calcium and phosphorus were higher and urine citrate and volume were lower in the thiosulfate-treated rats, changes that would increase calcium phosphate supersaturation. Thiosulfate treatment lowered urine pH, which would lower calcium phosphate supersaturation. Overall, there were no statistically significant differences in calcium phosphate supersaturation or upper limit of metastability between thiosulfate-treated and control rats. In vitro, thiosulfate only minimally affected ionized calcium, suggesting a mechanism of action other than calcium chelation. In summary, sodium thiosulfate reduces calcium phosphate stone formation in the genetic hypercalciuric rat. Controlled trials testing the efficacy and safety of sodium thiosulfate for recurrent kidney stones in humans are needed.

Figure 1.

Urine calcium and oxalate excretion and urine volume (mean ± SEM) in GHS rats fed a standard diet with (▪) or without STS ( ) added. *Different from control in the same time period, P < 0.001.

Figure 2.

Urine pH and urine citrate and ammonia excretion in GHS rats fed a standard diet with (▪) or without STS ( ) added. *Different from control in the same time period, P < 0.001; #different from control in the same time period, P < 0.05.

Figure 3.

Urine phosphorus, sulfate, and sodium excretion in GHS rats fed a standard diet with (▪) or without STS ( ) added. *Different from control in the same time period, P < 0.001.

Figure 4.

Urine CaP concentration product ratio, ULM and the difference of ULM and SS. #Different from control in the same time period, P < 0.05.

Figure 5.

Urine CaOx CPR, ULM, and the difference of ULM and SS. *Different from control in the same time period, P < 0.001.

Figure 6.

(A through D) Representative x-rays of the kidneys from four rats, two (A and B) in the control group with no STS therapy and two (C and D) that were treated with STS. Three of the four kidneys in the control group contain kidney stones; no stones are seen in the rats treated with STS.

Figure 7.

Effect of anions on ionized calcium. Citrate (▪) at increasing concentration lowers ionized calcium to a much greater extent than either sulfate (▴) or thiosulfate (•) in acetate buffer at pH 5.7 (left) or HEPES buffer at pH 7.2 (right).