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Adv Chronic Kidney Dis. 2019 Jul;26(4):253-266. doi: 10.1053/j.ackd.2019.04.004.

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

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Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Medical Cell Biology, Uppsala Universitet, Uppsala, Sweden; Department of Molecular Physiology & Biophysics and Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN. Electronic address:


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.


Anemia; Chronic kidney disease; Erythropoietin; Hypoxia-inducible factor; Prolyl hydroxylase domain


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