AST-120 for the management of progression of chronic kidney disease.
AST-120 for the management of progression of chronic kidney disease.
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DOI：
10.2147/ijnrd.s41339
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发表时间：
2014
影响因子：
2
通讯作者：
Niwa T
中科院分区：
文献类型：
--
作者：
Schulman G;Vanholder R;Niwa T
尿毒症毒素，如硫酸吲哚酚，通过促进肾小球硬化和间质纤维化，肾单位损失和血管损伤，促进慢性肾脏疾病（CKD）的发病机制。AST-120，一种口服肠道吸附剂，吸附吲哚，硫酸吲哚的前体，从而降低血清和尿中硫酸吲哚的浓度。AST-120自1991年起在日本上市，随后在韩国（2005年）和菲律宾（2010年）上市，作为延长CKD患者血液透析起始时间和改善尿毒症症状的药物。Medline检索了支持AST-120治疗CKD临床经验的数据。包括前瞻性开放标签和双盲试验以及回顾性分析。在前瞻性试验和回顾性分析中，AST-120已被证明可以延长血液透析开始的时间，减缓肾小球滤过率的下降和血清肌酐的升高。在美国最初的一项随机、双盲、安慰剂对照试验中，AST-120与血清硫酸吲哚酚水平的显著剂量依赖性降低和尿毒症相关不适的减少有关。评估CKD进展预防（EPPIC）试验，两项在北美/拉丁美洲和欧洲进行的双盲、安慰剂对照试验，正在评估AST-120预防CKD进展的疗效。EPPIC试验的结果将进一步确定AST-120在这种衰弱性疾病中的作用。
Uremic toxins such as indoxyl sulfate contribute to the pathogenesis of chronic kidney disease (CKD) by promoting glomerulosclerosis and interstitial fibrosis with loss of nephrons and vascular damage. AST-120, an orally administered intestinal sorbent, adsorbs indole, a precursor of indoxyl sulfate, thereby reducing serum and urinary concentrations of indoxyl sulfate. AST-120 has been available in Japan since 1991, and subsequently Korea (2005), and the Philippines (2010) as an agent to prolong the time to initiation of hemodialysis and for improvement of uremic symptoms in patients with CKD. A Medline search was performed to identify data supporting clinical experience with AST-120 for managing CKD. Prospective open-label and double-blind trials as well as retrospective analyses were included. In prospective trials and retrospective analyses, AST-120 has been shown to prolong the time to initiation of hemodialysis, and slow decline in glomerular filtration rate and the increase serum creatinine. In an initial randomized, double-blind, placebo-controlled trial in the United States, AST-120 was associated with a significant dose-dependent reduction in serum indoxyl sulfate levels and a decrease in uremia-related malaise. The Evaluating Prevention of Progression in CKD (EPPIC) trials, two double-blind, placebo-controlled trials undertaken in North America/Latin America and Europe, are evaluating the efficacy of AST-120 for preventing the progression of CKD. The results of the EPPIC trials will further define the role of AST-120 in this debilitating condition.