Hypoxia-inducible factor?prolyl hydroxylase inhibitors in the treatment of anemia of chronic kidney disease

Hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs) are a promising new class of orally administered drugs currently in late-stage global clinical development for the treatment of anemia of chronic kidney disease (CKD). HIF-PHIs activate the HIF oxygen-sensing pathway and are efficacious in correcting and maintaining hemoglobin levels in patients with non-dialysis- and dialysis-dependent CKD. In addition to promoting erythropoiesis through the increase in endogenous erythropoietin production, HIF-PHIs reduce hepcidin levels and modulate iron metabolism, providing increases in total iron binding capacity and transferrin levels, and potentially reducing the need for i.v. iron supplementation. Furthermore, HIF-activating drugs are predicted to have effects that extend beyond erythropoiesis. This review summarizes clinical data from current HIF-PHI trials in patients with anemia of CKD, discusses mechanisms of action and pharmacologic properties of HIF-PHIs, and deliberates over safety concerns and potential impact on anemia management in patients with CKD. Copyright (C) 2021, International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Automated summary

HIF-PHIs are a promising new class of orally administered drugs for the treatment of anemia of chronic kidney disease. They activate the HIF oxygen-sensing pathway, promoting erythropoiesis and modulating iron metabolism to potentially reduce the need for i.v. iron supplementation. These drugs are predicted to have effects beyond erythropoiesis.