HIF-PH Inhibitors versus Erythropoiesis-Stimulating Agents for Anemia of Chronic Kidney Disease: A Systematic Review

Abstract

Introduction: Anemia is a common complication of chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) are the standard treatment. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of oral agents for treating this condition. This review compares their efficacy and safety.

Methods: We conducted a search for RCTs that compared a HIF-PH inhibitor (e.g., roxadustat, daprodustat) to an ESA or placebo in CKD patients, both non-dialysis and dialysis-dependent. The primary outcome was the change in hemoglobin levels.

Results: The meta-analysis of 15 trials showed that HIF-PH inhibitors were non-inferior to ESAs in achieving and maintaining target hemoglobin levels. HIF-PH inhibitors also led to a reduction in cholesterol levels and improved iron utilization. The cardiovascular safety profiles were generally comparable to ESAs.

Discussion: As oral agents that mimic the body's natural response to hypoxia, HIF-PH inhibitors offer a novel and convenient alternative to injectable ESAs. Their effect on iron metabolism may reduce the need for intravenous iron.

Conclusion: HIF-PH inhibitors are an effective and safe oral treatment for anemia of chronic kidney disease, with efficacy non-inferior to ESAs.