Navigating Anemia Therapy in CKD With Hypoxia-Inducible Factor Activators: A Review

Area of Science:

• Nephrology
• Pharmacology
• Hematology

Background:

• Anemia in chronic kidney disease (CKD) presents clinical challenges, driving the need for novel treatments beyond erythropoiesis-stimulating agents (ESAs).
• Existing ESAs have associated safety concerns, necessitating alternative therapeutic strategies.

Purpose of the Study:

• To review the mechanism of action and clinical effects of Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) for anemia in CKD.
• To evaluate the safety profile of HIF-PHIs in comparison to ESAs, focusing on cardiovascular risks.
• To discuss the potential impact of HIF-PHIs on clinical practice, including use in kidney transplant recipients.

Main Methods:

• Review of existing literature on HIF-PHIs and ESAs in CKD anemia.
• Analysis of mechanisms of action, erythropoietic effects, and safety data.
• Comparative assessment of HIF-PHIs and ESAs regarding efficacy and safety concerns.

Main Results:

• HIF-PHIs are effective oral agents for increasing and maintaining hemoglobin levels in CKD patients.
• HIF-PHIs stimulate endogenous erythropoietin production and enhance iron metabolism.
• Cardiovascular safety concerns have limited the use of some HIF-PHIs in non-dialysis CKD patients.

Conclusions:

• HIF-PHIs represent a novel class of oral medications for managing anemia in CKD.
• Further investigation into cardiovascular safety is crucial for broader HIF-PHI application in CKD.
• HIF-PHIs may offer a valuable alternative to ESAs and have potential applications in kidney transplant recipients.