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

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) is a new therapy option for anemia in chronic kidney disease (CKD) patients. We aimed to evaluate evidence from randomized controlled trials (RCTs) on HIF-PHIs for anemia in non-dialysis dependent (NDD)-CKD patients. Materials and Methods: We searched three electronic databases (PubMed, CINAHL, Cochrane Central Register of Controlled Trials databases), trial registries, and manually screened reference list. Two authors independently conducted screening, data extraction, and assessed risk of bias. We used RevMan 5.3 for meta-analysis using standard methods. Certainty of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluations. Results: We included 12 RCTs involving 8611 patients with anemia of kidney disease. The studies included roxadustat (n = 2), daprodustat (n = 3), molidustat (n = 3), vadadustat (n = 2), enarodustat (n = 1), and desidustat (n = 1). Desidustat and daprodustat reported no difference in the hemoglobin levels from baseline up to 24-52 weeks as compared to darbepoetin alpha [Mean Difference (MD): 0.09 g/dL (CI 95% 0.15-0.33); p = 0.46; 529 participants; low certainty evidence; and MD: 0.08 g/dL (CI 95% 0.08-0.08); p < 0.00001; two studies; 4089 participants; low certainty evidence, respectively]. Broadly, HIF-PHI molecules exhibited little difference when compared to other alternatives like erythropoietin stimulating agents (ESAs), but the evidence is not of high certainty. Conclusion: Our meta-analysis provides evidence on the use of HIF-PHIs as an alternative to ESAs for anemia in NDD-CKDs.