The broad objective of this proposed research is to determine the effect of sodium thiosulfate on kidney stone formation. The drug will initially be studied in a rat model of nephrolithiasis and if the drug is shown to reduce risk of new stone formation we will study the drug in patients with nephrolithiasis. The long term goal is to bring a new therapy for kidney stones to market. At the present time there are three pharmacologic therapies for calcium nephrolithiasis that have been proven effective in prospective placebo controlled trials, thiazide diuretics, potassium citrate salts, and allopurinol. Sodium thiosulfate is a generic drug that is considered to be safe for use in humans. A single trial showed sodium thiosulfate to be effective in preventing stone formation in patients with recurrent calcium nephrolithiasis, though no formal control group was included in the study. However, little additional data concerning the use of sodium thiosulfate for nephrolithiasis has been published. Recently, sodium thiosulfate has been reported to be effective in treating pathologic soft tissue calcium phosphate deposition in patients with renal failure, supporting the premise that it possesses significant anti-crystal activity. At this time, sodium thiosulfate remains a promising but incompletely studied potential therapeutic agent; in particular there are no clearly defined mechanisms of action that have been established. If we could show that sodium thiosulfate reduces urine saturation of calcium salts, increases urine inhibition of crystallization and/or reduces stone formation in an animal model it would justify the expense and difficulty of a formal human trial.
The aims of this proposal are to determine if sodium thiosulfate can reduce calcium oxalate and calcium phosphate stone formation and/or reduce urine crystallization potential in hypercalciuric kidney stone forming rats. Kidney stones are a very common problem, affecting 13% of men and 7% of women in the United States. Over half of people with kidney stones will have a recurrence of stone formation and many of these patients receive treatment to prevent new stones. New, more effective and better tolerated drugs are needed to reduce the recurrence of kidney stones in these patients. ? ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-RUS-D (12))
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Mullins, Christopher V
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Litholink Corporation
United States
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Asplin, John R; Donahue, Susan E; Lindeman, Christina et al. (2009) Thiosulfate reduces calcium phosphate nephrolithiasis. J Am Soc Nephrol 20:1246-53
Bushinsky, D A; Michalenka, A C; Strutz, K L et al. (2008) Effect of bolus and divided feeding on urine ions and supersaturation in genetic hypercalciuric stone-forming rats. Kidney Int 73:423-9