Cao Jing-Yuan, Liu Bi-Cheng
Institute of Nephrology, Zhongda Hospital, Southeast University, Nanjing 210009, China.
Sheng Li Xue Bao. 2018 Dec 25;70(6):623-629.
Renal anemia, mainly caused by the deficiencies of erythropoietin (EPO) and iron metabolism disorder, is one of the most common complications of chronic kidney disease. Hypoxia-inducible factor (HIF) is a class of transcription factors responsible for maintaining homeostasis during oxygen deprivation. In normoxia, HIF is degraded by prolyl hydroxylase (PHD). While under hypoxic conditions, the hydroxylation activity of PHD is inhibited, and the cellular concentration of HIF is elevated, resulting in an increase in endogenous EPO production and iron absorption. Therefore, this regulating pathway, also termed as the HIF-PHD axis, has become a promising therapeutic target of treating renal anemia. Several innovative drugs acting as selective HIF-PHD inhibitors have been successfully developed in the past years, and some of them are undergoing clinical trials. In this review, we will introduce the definition and regulatory mechanism of HIF-PHD axis, as well as current insights into its physiologic and therapeutic role in renal anemia.
肾性贫血主要由促红细胞生成素（EPO）缺乏和铁代谢紊乱引起，是慢性肾脏病最常见的并发症之一。缺氧诱导因子（HIF）是一类在缺氧期间负责维持体内平衡的转录因子。在常氧状态下，HIF被脯氨酰羟化酶（PHD）降解。而在缺氧条件下，PHD的羟化活性受到抑制，HIF的细胞浓度升高，导致内源性EPO生成增加和铁吸收增加。因此，这条调控途径，也被称为HIF-PHD轴，已成为治疗肾性贫血的一个有前景的治疗靶点。在过去几年中，几种作为选择性HIF-PHD抑制剂的创新药物已成功研发出来，其中一些正在进行临床试验。在这篇综述中，我们将介绍HIF-PHD轴的定义和调控机制，以及目前对其在肾性贫血中的生理和治疗作用的见解。
