Potential Pharmacologic Treatments for Cystinuria and for Calcium Stones Associated with Hyperuricosuria
Potential Pharmacologic Treatments for Cystinuria and for Calcium Stones Associated with Hyperuricosuria
复制标题
DOI：
10.2215/cjn.00320111
复制
发表时间：
2011-08-01
影响因子：
9.8
通讯作者：
Goldfarb, David S.
中科院分区：
文献类型：
--
作者：
Goldfarb, David S.
两个新的潜在的药物治疗复发性结石病的描述。高尿酸血症在促进钙结石中的作用是有争议的，只有一些但不是所有的流行病学研究表明尿尿酸排泄增加和钙结石疾病之间的关联。尿酸在体外“盐析”草酸钙（或降低草酸钙的溶解度）的能力支持了这种关系。在高尿酸尿和正常钙尿患者中进行的一项别嘌呤醇随机对照试验也能有效预防结石复发。非布司他是一种黄嘌呤氧化酶（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，可能比别嘌呤醇更有优势，目前正在进行类似的试验，最终目的是确定降尿酸治疗是否能预防钙结石复发。在过去的30年里，胱氨酸尿症的治疗进展甚微。最近已经使用原子力显微镜来证明胱氨酸晶体生长的有效抑制在低浓度的L-胱氨酸甲酯和L-胱氨酸二甲酯（提供晶体生长的空间抑制的胱氨酸的结构类似物）下完成。在体外，L-胱氨酸二甲酯对晶体生长有明显的抑制作用。该药物的安全性和有效性将在作为胱氨酸尿症动物模型的Slc 3a 1基因敲除小鼠中进行测试。Clin J Am Soc Nephrol 6：2093-2097，2011. doi：10.2215/CJN.00320111
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. Clin J Am Soc Nephrol 6: 2093-2097, 2011. doi:10.2215/CJN.00320111