Ishii Taisuke, Tanaka Tetsuhiro, Nangaku Masaomi
Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Ther Clin Risk Manag. 2021 Feb 17;17:155-163. doi: 10.2147/TCRM.S293879. eCollection 2021.
Anemia is a major complication of chronic kidney disease (CKD), which mainly results from appropriate erythropoietin production impairment. Prolyl hydroxylase domain (PHD) inhibitors are currently being developed and approved in some countries as a new treatment for CKD patients with anemia due to the stabilization of intracellular hypoxia-inducible factor (HIF) 1α and HIF2α by PHD inhibition. Daprodustat is one of the orally administrated small-molecule HIF-PH inhibitors, leading to an increase in erythropoietin production, which is regulated by HIF. Also, daprodustat is expected to improve iron metabolism. Recently, several clinical trials showed its efficacy and safety in both hemodialysis- and non-hemodialysis- dependent CKD patients. In addition, some international Phase 3 studies are underway to confirm these effects and reveal the safety profile. This article summarizes the development process and results of each clinical trial.
贫血是慢性肾脏病（CKD）的主要并发症，主要由促红细胞生成素生成受损所致。脯氨酰羟化酶结构域（PHD）抑制剂目前正在研发中，并且在一些国家已获批，作为一种针对因PHD抑制使细胞内缺氧诱导因子（HIF）1α和HIF2α稳定而导致贫血的CKD患者的新疗法。达普司他是口服小分子HIF-PH抑制剂之一，可导致由HIF调节的促红细胞生成素生成增加。此外，达普司他有望改善铁代谢。最近，多项临床试验显示了其在依赖血液透析和不依赖血液透析的CKD患者中的疗效和安全性。此外，一些国际3期研究正在进行中，以确认这些效果并揭示安全性。本文总结了各项临床试验的研发过程和结果。
