Novel Anemia Treatment: HIF-PH Inhibitors

  • 1 Daniel W. Coyne, MD, is professor of medicine, Washington University, St. Louis, MO.
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For more than 30 years, erythropoiesis-stimulating agents (ESAs) have reigned supreme as the treatment for chronic kidney disease (CKD)–related anemia. Can hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) topple ESAs? HIF-PHIs are oral medications taken three times a week or daily and have been shown in trials to achieve and maintain goal hemoglobin to the same degree as ESAs. HIF-PHIs are small molecules that inhibit the prolyl hydroxylase enzyme that continually marks the HIF for degradation. Each dose transiently increases intracellular HIF2a, a transcription factor, leading to activation of a series of genes, including erythropoietin (EPO) and several iron transport genes. Consequently,