Treatment of Calcium Nephrolithiasis Sodium Thiosulfate

描述(由申请人提供)：这项拟议研究的广泛目标是确定硫代硫酸钠对肾结石形成的影响。该药物最初将在肾结石的大鼠模型中进行研究，如果该药物被证明能降低新结石形成的风险，我们将研究该药物在肾结石患者中的应用。长期目标是将一种治疗肾结石的新疗法推向市场。目前，在前瞻性的安慰剂对照试验中，有三种药物治疗钙性肾结石被证明是有效的，它们是噻嗪类利尿剂、柠檬酸钾和别嘌醇。硫代硫酸钠是一种被认为对人体安全的仿制药。一项单独的试验表明，硫代硫酸钠对预防复发性钙肾结石患者的结石形成有效，尽管研究中没有包括正式的对照组。然而，关于使用硫代硫酸钠治疗肾结石的补充数据很少发表。最近，硫代硫酸钠被报道有效地治疗肾功能衰竭患者的病理性软组织钙磷沉积，支持了它具有显著的抗结晶活性的前提。目前，硫代硫酸钠仍然是一种有希望但尚未完全研究的潜在治疗剂；特别是目前还没有明确定义的作用机制。如果我们能在动物模型中证明硫代硫酸钠降低了钙盐的尿液饱和度，增加了尿液对结晶的抑制和/或减少了结石的形成，这将证明正式的人体试验的费用和难度是合理的。这项建议的目的是确定硫代硫酸钠是否可以减少高钙尿性肾结石形成大鼠草酸钙和磷酸钙结石的形成和/或降低尿液结晶潜能。肾结石是一个非常常见的问题，在美国，13%的男性和7%的女性会受到影响。超过一半的肾结石患者会复发形成结石，其中许多患者都接受了预防新结石的治疗。需要新的、更有效、耐受性更好的药物来减少这些患者肾结石的复发。

DESCRIPTION (provided by applicant): 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.