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

Nephron. 2020;144(11):572-582. doi: 10.1159/000508812. Epub 2020 Aug 31.

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.

Keywords: Hypoxia-inducible factor prolyl hydroxylase inhibitors; Meta-analysis; Renal anemia.

Publication types

  • Meta-Analysis

MeSH terms

  • Anemia / complications
  • Anemia / drug therapy*
  • Anemia / metabolism
  • Hemoglobins / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Prolyl-Hydroxylase Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / metabolism

Substances

  • Hemoglobins
  • Hypoxia-Inducible Factor 1
  • Prolyl-Hydroxylase Inhibitors