Efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) on anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD): a systematic review and meta-analysis

Abstract

Purpose: HIF-PHI (hypoxia-inducible factor prolyl hydroxylase inhibitor) was developed to improve renal anemia. This study was to evaluate the efficiency and safety of HIF-PHI in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).

Methods: The literature was extracted from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and the Wanfang database. Statistical tests and forest plots were depicted by Review Manager Version 5.3. The primary outcome was a change in hemoglobin level from baseline (ΔHb). Secondary outcomes were changes in ferritin (ΔFerritin), hepcidin (ΔHepcidin), and transferrin saturation from baseline (ΔTSAT), and adverse events (AEs). This study is registered with PROSPERO (registration number CRD42020199656).

Results: Ten trials were included. The results showed that HIF-PHI improved the ΔHb [SMD 3.03 (95% CI 2.10, 3.96), P < 0.00001] in NDD patients. HIF-PHI reduced hepcidin levels in the NDD patients [SMD - 1.44 (95% CI - 2.19-0.70), P = 0.0002]. ΔFerritin values were reduced significantly in the HIF-PHI group [SMD - 1.08 (95% CI - 1.63-0.53), P = 0.0001]. However, ΔTSAT values showed no significant difference in the HIF-PHI group compared to the placebo group [SMD - 0.23 (95% CI - 0.66-0.21), P = 0.31]. In the safety assessment, HIF-PHI did not increase adverse events significantly [RR 0.98 (95% CI 0.88-1.10), P = 0.74].

Conclusion: HIF-PHI improves renal anemia and iron utilization disorder in NDD-CKD patients, without significantly more adverse events.

Keywords: Chronic kidney disease; Hypoxia-inducible factor prolyl hydroxylase inhibitor; Meta-analysis; Renal anemia.