Department of Renal Medicine, King's College Hospital, London, UK.
Curr Opin Nephrol Hypertens. 2022 Sep 1;31(5):399-405. doi: 10.1097/MNH.0000000000000813. Epub 2022 Jul 15.
Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors have recently been developed as a new treatment for anemia associated with chronic kidney disease (CKD). Several of these have been approved in Europe (roxadustat), China, and Japan, but none approved in the United States to date, although daprodustat has been submitted as a new drug application to the Food and Drug Administration. The aim of this review is to critically appraise the available data, particularly the most recent publications, and offer a personal viewpoint on whether or not these drugs are ready for primetime.
The efficacy of HIF prolyl hydroxylase inhibitors in improving CKD anemia and maintaining a higher hemoglobin is undisputed, but there remain some concerns about safety, particularly in the long term. Some of the safety concerns may result from an exaggerated pharmacological response, while other potential adverse effects could be due to transcriptional effects of these agents beyond genes involved in erythropoiesis.
HIF prolyl hydroxylase inhibitors are already being used in clinical practice in several countries of the world, and ongoing research is being conducted to define the role of these drugs not only in the management of anemia but also beyond into other clinical settings.
缺氧诱导因子（HIF）脯氨酰羟化酶抑制剂最近已被开发为治疗慢性肾脏病（CKD）相关贫血的新方法。其中一些已在欧洲（罗沙司他）、中国和日本获得批准，但截至目前尚未在美国获得批准，尽管达普司他已被提交给美国食品和药物管理局作为新药申请。本综述的目的是批判性地评估现有数据，特别是最近的出版物，并就这些药物是否已经准备好投入使用提供个人观点。
HIF 脯氨酰羟化酶抑制剂在改善 CKD 贫血和维持更高的血红蛋白方面的疗效是毋庸置疑的，但仍存在一些安全性问题，特别是在长期方面。一些安全性问题可能是由于药理学反应过度，而其他潜在的不良反应可能是由于这些药物除了参与红细胞生成的基因之外，还具有转录效应。
HIF 脯氨酰羟化酶抑制剂已经在世界上几个国家的临床实践中使用，目前正在进行研究，以确定这些药物的作用不仅在贫血的治疗中，而且在其他临床环境中。
