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

  • Neil S. Sanghani
    Affiliations
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
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  • Volker H. Haase
    Correspondence
    Address correspondence to Volker H. Haase, MD, Division of Nephrology & Hypertension, Department of Medicine, Vanderbilt University Medical Center, C-3119A MCN, 1161 21st Avenue So., Nashville, TN 37232-2372.
    Affiliations
    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
    Search for articles by this author
      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.

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