Hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience.

Sanghani NS, Haase VH
Adv Chronic Kidney Dis. 2019 26 (4): 253-266

PMID: 31477256 · PMCID: PMC7318915 · DOI:10.1053/j.ackd.2019.04.004

Prolyl hydroxylase domain oxygen sensors are dioxygenases that regulate the activity of hypoxia-inducible factor (HIF), which controls renal and hepatic erythropoietin production and coordinates erythropoiesis with iron metabolism. Small molecule inhibitors of prolyl hydroxylase domain dioxygenases (HIF-PHI [prolyl hydroxylase inhibitor]) stimulate the production of endogenous erythropoietin and improve iron metabolism resulting in efficacious anemia management in patients with CKD. Three oral HIF-PHIs-daprodustat, roxadustat, and vadadustat-have now advanced to global phase III clinical development culminating in the recent licensing of roxadustat for oral anemia therapy in China. Here, we survey current clinical experience with HIF-PHIs, discuss potential therapeutic advantages, and deliberate over safety concerns regarding long-term administration in patients with renal anemia.

Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

MeSH Terms (9)

Anemia Barbiturates Glycine Humans Isoquinolines Picolinic Acids Prolyl-Hydroxylase Inhibitors Renal Insufficiency, Chronic Treatment Outcome

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