Treatment of Calcium Nephrolithiasis Sodium Thiosulfate

硫代硫酸钠治疗钙肾结石

• 批准号: 7426132
• 负责人: JOHN R ASPLIN
• 金额: $ 16.47万
• 依托单位: LITHOLINK CORPORATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7426132
• 关键词: calcium phosphate; chemoprevention; crystallization; dietary supplements; disease /disorder model; dosage; drug screening /evaluation; hydroxyproline; hypercalciuria; kidney disorder chemotherapy; kidney pharmacology; laboratory rat; nephrolithiasis; nonhuman therapy evaluation; oral administration; oxalates; sodium; therapy design /development; thiosulfate; urinalysis

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.

描述（由申请人提供）：本拟议研究的主要目的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大鼠模型中进行研究，如果该药物显示可降低新结石形成的风险，我们将在肾结石患者中研究该药物。长期目标是将肾结石的新疗法推向市场。目前，有三种药物治疗钙肾结石，已被证明是有效的前瞻性安慰剂对照试验，噻嗪类利尿剂，柠檬酸钾盐，别嘌呤醇。硫代硫酸钠是一种仿制药，被认为可安全用于人类。一项单一的试验表明，硫代硫酸钠可有效预防复发性钙肾结石患者的结石形成，尽管研究中没有正式的对照组。然而，很少有关于使用硫代硫酸钠治疗肾结石的额外数据已发表。最近，据报道，硫代硫酸钠可有效治疗肾衰竭患者的病理性软组织磷酸钙沉积，支持其具有显著抗结晶活性的前提。目前，硫代硫酸钠仍是一种有前景但尚未完全研究的潜在治疗剂;特别是尚未确定明确的作用机制。如果我们能够证明硫代硫酸钠在动物模型中降低了钙盐的尿液饱和度，增加了尿液对结晶的抑制和/或减少了结石形成，那么正式人体试验的费用和难度将是合理的。本提案的目的是确定硫代硫酸钠是否可以减少草酸钙和磷酸钙结石形成和/或降低高尿钙肾结石形成大鼠的尿液结晶潜力。肾结石是一种非常常见的问题，影响美国13%的男性和7%的女性。超过一半的肾结石患者会复发结石形成，其中许多患者接受治疗以防止新的结石。需要新的、更有效的和更好耐受的药物来减少这些患者肾结石的复发。