Nephrology Section/111G, NY DVAMC, 423 E. 23 Street, New York, NY 10010, USA.
Clin J Am Soc Nephrol. 2011 Aug;6(8):2093-7. doi: 10.2215/CJN.00320111. Epub 2011 Jul 14.
Two new potential pharmacologic therapies for recurrent stone disease are described. The role of hyperuricosuria in promoting calcium stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and calcium stone disease. The relationship is supported by the ability of uric acid to "salt out" (or reduce the solubility of) calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantages over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent calcium stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of l-cystine methyl ester and l-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, l-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug's safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria.
描述了两种新的潜在的用于复发性结石病的药物治疗方法。高尿酸尿症在促进钙结石形成中的作用存在争议，只有部分而不是所有的流行病学研究表明尿尿酸排泄增加与钙结石病之间存在关联。尿酸能够“盐析”（或降低）体外草酸钙的溶解度，这支持了这种关联。一项在高尿酸尿和正常钙尿患者中进行的别嘌醇随机对照试验也有效地预防了复发性结石。黄嘌呤氧化酶（也称为黄嘌呤脱氢酶或黄嘌呤氧化还原酶）的非嘌呤抑制剂非布司他可能比别嘌醇更有优势，并且正在按照类似的方案进行测试，最终目的是确定尿酸降低疗法是否可以预防复发性钙结石。胱氨酸尿症的治疗在过去 30 年中几乎没有进展。最近，原子力显微镜已被用于证明，低浓度的 l-胱氨酸甲酯和 l-胱氨酸二甲基酯可有效抑制胱氨酸晶体生长，这两种结构类似物可提供晶体生长的空间位阻抑制。在体外，l-胱氨酸二甲基酯对晶体生长有显著的抑制作用。该药物的安全性和有效性将在 Slc3a1 敲除小鼠中进行测试，Slc3a1 敲除小鼠是胱氨酸尿症的动物模型。
