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Kidney Week

Abstract: TH-PO987

Long-Term Safety of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in CKD: A Systematic Review and Meta-Analysis of Randomized Trials

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Ha, Jeffrey, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Hiremath, Swapnil, University of Ottawa, Ottawa, Ontario, Canada
  • Jun, Min, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Palmer, Suetonia, University of Otago, Dunedin, New Zealand
  • Wheeler, David C., University College London, London, United Kingdom
  • Coyne, Daniel W., Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Perkovic, Vlado, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Badve, Sunil, The George Institute for Global Health, Newtown, New South Wales, Australia
Background

Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). We assessed long-term safety of HIF prolyl hydroxylase inhibitors in CKD.

Methods

In this systematic review and meta-analysis, MEDLINE, Embase and Cochrane databases were searched to March 2023. Randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with ≥48 weeks of follow-up were eligible. Major adverse cardiovascular events (MACE), individual components of composite cardiovascular endpoints, thrombotic events, and non-cardiovascular adverse events were evaluated. We conducted analyses separately in people with CKD treated with dialysis and those not treated with dialysis (PROSPERO registration CRD42021278011).

Results

Twenty-five trials involving 26,478 participants proved eligible. Of these, 13 trials were conducted in 13,230 participants with dialysis-dependent CKD, and 12 trials involved 13,248 participants with CKD not requiring dialysis. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (relative risk [RR] 0.99, 95% CI 0.92 to 1.08) and non-dialysis CKD (RR 1.08, 95% CI 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (RR 1.10, 95% CI 0.96 to 1.27) in people with non-dialysis CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE, and for cardiovascular death. The safety of HIF prolyl hydroxylase inhibitors for other outcomes was similar to ESA in dialysis-dependent CKD. In non-dialysis CKD, dialysis access thrombosis, infections, hyperkalemia and seizures occurred more frequently in the HIF prolyl hydroxylase inhibitor group than the placebo group. In non-dialysis CKD, esophageal or gastric erosion was more frequent with HIF prolyl hydroxylase inhibitors than ESA.

Conclusion

The long-term effects of HIF prolyl hydroxylase inhibitors were similar to ESA in dialysis-dependent CKD. However, HIF prolyl hydroxylase inhibitors increased the incidence of some adverse outcomes in non-dialysis CKD.