A spotlight on using HIF-PH inhibitors in renal anemia

Expert Opin Pharmacother. 2024 Jul;25(10):1291-1299. doi: 10.1080/14656566.2024.2378903. Epub 2024 Jul 17.

Abstract

Introduction: Erythropoiesis-stimulating agents (ESAs) together with iron supplementation had been the standard treatment for anemia in chronic kidney disease (CKD) for the past decades. Recently, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have attracted attention as a novel treatment option.

Areas covered: This review summarizes the effectiveness and the safety of HIF-PHIs based on previous clinical trials and discusses points to consider for their clinical use.

Expert opinion: The results from clinical trials demonstrate that HIF-PHIs are non-inferior to ESAs in terms of the efficacy to maintain or improve blood hemoglobin levels. However, concerns about adverse events including cardiovascular outcomes, thrombotic events, and tumor progression have prevented HIF-PHIs from being widely approved for clinical use. Also, long-term safety has not been demonstrated yet. Practically, HIF-PHIs should be used with caution in patients with a history of thrombosis or active malignancy. Patients without them may be preferable for HIF-PHIs if those are bothered with regular injections of ESAs or are hyporesponsive to ESAs without obvious reasons, provided that the drugs were approved in the country. Even so, clinicians must take caution for signs of adverse events such as heart failure after prescribing the drugs.

Keywords: Hypoxia-inducible factor-prolyl hydroxylase inhibitors; anemia; chronic kidney disease; dialysis; erythropoiesis-stimulating agents.

Publication types

  • Review

MeSH terms

  • Anemia* / drug therapy
  • Animals
  • Hematinics* / adverse effects
  • Hematinics* / therapeutic use
  • Hemoglobins / metabolism
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases* / antagonists & inhibitors
  • Prolyl-Hydroxylase Inhibitors / adverse effects
  • Prolyl-Hydroxylase Inhibitors / pharmacology
  • Prolyl-Hydroxylase Inhibitors / therapeutic use
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy

Substances

  • Hematinics
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Hemoglobins
  • Prolyl-Hydroxylase Inhibitors