Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in Patients with Renal Anemia: A Meta-Analysis of Randomized Trials

Abstract

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of treatment for renal anemia in patients with chronic kidney disease (CKD). This meta-analysis was designed to evaluate their efficacy and safety. Method: Eight databases were searched for randomized controlled trials (RCTs). Information about efficacy and safety was extracted and combined using random-effects or fixed-effects models, depending on heterogeneity. Risk of bias was assessed using the method recommended by the Cochrane Centre. Results: Nineteen articles on RCTs were selected, involving 3,289 participants. We found that HIF-PHIs improved the level of hemoglobin (Hb) (weighted mean difference [WMD] 1.40; 95% CI: 0.96–1.84; p < 0.001), response rate of Hb (risk ratio [RR] 5.95; 95% CI: 3.95–8.96; p < 0.001), and total iron-binding capacity (WMD 42.94; 95% CI: 31.39–54.49; p < 0.001), while reducing the level of hepcidin (WMD −40.42; 95% CI: −50.44 to −30.39; p < 0.001), ferritin (WMD −64.60; 95% CI: −78.56 to −50.64; p < 0.001), and transferrin saturation (WMD −5.57; 95% CI: −8.53 to −2.61; p < 0.001). Meanwhile, there was no evidence of effect on serum iron (WMD 1.60; 95% CI: −3.72 to 6.93; p = 0.55), nor on the incidence of adverse events (AEs) (RR 1.06; 95% CI: 0.99–1.15; p = 0.51) or of serious adverse events (SAEs) (RR 1.14; 95% CI: 0.88–1.46; p = 0.32). Conclusion: HIF-PHIs ameliorate renal anemia and rectify iron metabolism in the short term without increasing the incidence of AEs and SAEs.