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Hypoxia-Inducible Factor Stabilization as an Emerging Therapy for CKD-Related Anemia: Report From a Scientific

Jay B Wish1, Kai-Uwe Eckardt2, Csaba P Kovesdy3

  • 1Department of Medicine, School of Medicine, Indiana University, Indianapolis, Indiana.

American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
|July 31, 2021
PubMed

Insights

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) show promise for treating anemia in chronic kidney disease (CKD) patients. Further research is recommended on their long-term safety and implementation strategies.

Area of Science:

  • Nephrology
  • Pharmacology
  • Biochemistry

Background:

  • Anemia is a common complication in chronic kidney disease (CKD).
  • Current treatments for anemia in CKD have limitations.
  • Hypoxia-inducible factor (HIF) pathway plays a crucial role in red blood cell production.

Purpose of the Study:

  • To discuss the potential role of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) in treating anemia in CKD patients.
  • To review current understanding of HIF biology and HIF-PHI pharmacology.
  • To summarize findings from Phase 2 and Phase 3 clinical trials of HIF-PHIs in CKD.

Main Methods:

  • Convened an international, interdisciplinary workshop.
  • Reviewed existing literature on HIF biology, HIF-PHI pharmacology, and clinical trial data.
  • Included experts in physiology, biochemistry, translational medicine, and clinical management.

Main Results:

  • HIF-PHIs represent a new class of agents for anemia in CKD.
  • Phase 2 and Phase 3 trial data were reviewed, including patients on and off dialysis.
  • Key findings from available Phase 3 trials were incorporated.

Conclusions:

  • HIF-PHIs offer a potential new therapeutic option for CKD-related anemia.
  • Recommendations were developed for further research, focusing on long-term safety and implementation.
  • Considerations for patient and provider education were highlighted.

Keywords:
Anemiachronic kidney disease (CKD)daprodustatdialysisenarodustatend-stage renal disease (ESRD)erythropoiesishemoglobinhypoxia-inducible factor (HIF)prolyl hydroxylase inhibitor (PHI)roxadustatvadadustat

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