Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in Dialysis-Dependent Chronic Kidney Disease: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are oral drugs for patients with renal anemia. This study aimed to synthesize evidence on HIF-PHIs for anemia in dialysis-dependent chronic kidney disease (DD-CKD) patients. We searched PubMed, CINAHL, and Cochrane Central Register of Controlled Trials databases and trial registries for randomized controlled trials (RCTs) reporting HIF-PHIs versus erythropoietin-stimulating agents (ESA) for anemia in DD-CKD patients. Two authors independently conducted screening, data extraction, and assessed risk of bias. We used RevMan 5.3 software for meta-analysis using standard methods. Certainty of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). We included 20 RCTs involving 14,999 patients with anemia of kidney disease. The studies included roxadustat (n = 9), daprodustat (n = 5), vadadustat (n = 2), molidustat (n = 2), enarodustat (n = 1), and desidustat (n = 1). Overall, daprodustat as an alternative to ESAs reported a substantial net benefit while roxadustat showed more damage than benefit as compared to ESAs. While other HIF inhibitors demonstrated little to no difference or small benefit, daprodustat reduces the need for intravenous iron supplementation up to 52 weeks as compared to ESAs [Odds Ratio (OR): 0.77 (95% CI 0.53-1.13); p = 0.18; two studies; 674 participants; moderate certainty evidence]. Roxadustat increased treatment-emergent adverse events up to 6-52 weeks as compared to ESAs [OR: 1.45 (95% CI 1.08-1.96); p = 0.01; six studies; 1715 participants; moderate certainty evidence]. The study provided evidence on the use of HIF-PHIs for treating renal anemia in DD-CKD patients as an alternative to ESAs.