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

Haase VH
Kidney Int Suppl (2011). 2021 11 (1): 8-25

PMID: 33777492 · PMCID: PMC7983025 · DOI:10.1016/j.kisu.2020.12.002

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.

© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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