Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2372, USA.
J Ren Nutr. 2012 Jan;22(1):107-13. doi: 10.1053/j.jrn.2011.10.035.
Fibrosis plays a major role in the pathogenesis of progressive chronic kidney disease (CKD). The inhibition of the renin-angiotensin system, which promotes fibrosis, has become the standard of care in the treatment of patients with CKD. The use of alternative agents capable of blocking the actions of profibrotic cytokines such as transforming growth factor-beta (TGF-β) is also an important strategy that is in its early stages of development. An example of such a drug is AST-120, a charcoal compound that ultimately inhibits the synthesis of TGF-β in the kidney. The inhibition is mediated by blocking the intestinal absorption of tryptophan-derived indole by AST-120. This reduces the hepatic conversion of indole to indoxyl sulfate (IS). IS stimulates the production of TGF-β in the renal parenchyma, and lowering the level of IS with AST-120 appears to slow progression of CKD. The status of recent trials examining the safety and efficacy of AST-120 has been described, including a multicenter, randomized, placebo-controlled, phase III trial of approximately 2,000 subjects being conducted to gain approval of this drug by the U.S. Food and Drug Administration.
纤维化在慢性肾脏病（CKD）的发病机制中起着主要作用。抑制促进纤维化的肾素-血管紧张素系统已成为 CKD 患者治疗的标准。使用能够阻断促纤维化细胞因子（如转化生长因子-β[TGF-β]）作用的替代药物也是一种重要的策略，目前正处于早期开发阶段。AST-120 就是这样一种药物，它是一种木炭化合物，最终可抑制肾脏中 TGF-β的合成。这种抑制作用是通过 AST-120 阻断色氨酸衍生吲哚在肠道中的吸收来介导的。这减少了吲哚在肝脏中转化为吲哚硫酸（IS）。IS 刺激肾实质中 TGF-β的产生，用 AST-120 降低 IS 的水平似乎可减缓 CKD 的进展。本文描述了最近检查 AST-120 安全性和疗效的试验状况，包括一项涉及约 2000 名受试者的多中心、随机、安慰剂对照、III 期试验，旨在获得美国食品和药物管理局对该药的批准。
