Kidney Week Educational Symposia-Treatment of Anemia of CKD: What Is the Role of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors?

Video Transcription

Video Summary

The symposium reviewed current treatment of anemia in chronic kidney disease (CKD) and the emerging role of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). Moderator Wendy St. Peter emphasized that anemia remains common yet undertreated, especially in non-dialysis CKD, where use of ESAs and IV iron has declined since cardiovascular safety trials (e.g., TREAT), while transfusions have become relatively more common. She highlighted the need for more individualized, patient-centered anemia care, better patient-reported outcome tools, and attention to caregiver burden.<br /><br />Dr. Daniel Coyne presented the scientific rationale and clinical trial evidence for HIF-PHIs. He traced the discovery of oxygen sensing and erythropoietin regulation through the HIF pathway (Nobel Prize–winning work), explaining that HIF-PHIs stabilize HIF to increase endogenous EPO and influence iron handling (e.g., reduced hepcidin, increased transferrin/TIBC). In large dialysis trials (e.g., with vadadustat and daprodustat), HIF-PHIs maintained hemoglobin similarly to ESAs and showed comparable major adverse cardiovascular event (MACE) outcomes. A meta-analysis across >12,000 patients found no difference in MACE, mortality, MI, stroke, or heart failure versus ESAs, with a possible lower atrial fibrillation risk. Available trial data did not show increased cancer incidence, though long-term malignancy risk remains a concern.<br /><br />Dr. Jay Wish focused on practice integration and U.S. regulatory realities. He outlined potential niches where HIF-PHIs may help: ESA hyporesponsiveness (often inflammation/hepcidin-related) and home dialysis (oral dosing convenience). He reviewed differences among agents and noted that in U.S. dialysis care, daprodustat appears to be exiting the market, while vadadustat is approved for patients on dialysis ≥3 months with daily dosing and is expected to launch in 2025. HIF-PHIs are bundled into U.S. dialysis payments, affecting access and prescribing logistics. Discussion concluded that hemoglobin targets are unlikely to rise in the U.S., and clinicians should improve anemia assessment and treatment rather than relying on transfusions.

Asset Subtitle

Moderator(s): Wendy St. Peter

Presentation(s):

Introduction - Wendy St. Peter
The Science behind HIF-PHI Development: From Bench to Clinical Trials - Daniel Coyne
Incorporating HIF-PHIs into Clinical Practice - Jay Wish

Support is provided by an educational grant from Akebia Therapeutics, Inc.

Meta Tag

Date 10/25/2024

Pathway 1 Dialysis

Pathway 2 Pharmacology

Session ID 496814

Session Type ES - Educational Symposium

Keywords

anemia in chronic kidney disease

CKD non-dialysis anemia management

hypoxia-inducible factor prolyl hydroxylase inhibitors

HIF pathway erythropoietin regulation

erythropoiesis-stimulating agents safety trials TREAT

intravenous iron use and hepcidin

dialysis clinical trials vadadustat daprodustat

major adverse cardiovascular events meta-analysis

ESA hyporesponsiveness inflammation

U.S. dialysis payment bundling and regulatory approval