P NATALE 1,2,S PALMER 3, A TONG 1, M RUOSPO 2, E HODSON 1,4, T COOPER 1,4, D HAHN 5, J CRAIG 6, G STRIPPOLI 1,2,4
1University Of Sydney, Australia, 2University of Bari, Italy, 3University of Otago, New Zealand, 4Cochrane Kidney and Transplant, Australia, 5Children’s Hospital at Westmead, Australia, 6Flinders University, Australia
Aim: To evaluate effects of hypoxia-inducible factors (HIF) stabilisers for the management of anaemia in people with chronic kidney disease.
Background:Anaemia occurs in chronic kidney disease (CKD) and is associated with death and cardiovascular disease. Oral HIF stabilisers are now available to manage anaemia in people with CKD.
Methods: We included randomised controlled trials evaluating HIF stabilisers compared to placebo, standard care, erythropoiesis-stimulating agents (ESA) or iron supplementation in people with CKD. Effects of treatment were estimated using random effects meta-analysis. Evidence certainty was evaluated using GRADE.
Results: 33 studies (15,941 participants) proved eligible. Compared to placebo, HIF stabilisers had uncertain effects on cardiovascular death (11 studies, 1517 participants: RR 3.68, 95% CI 0.19 to 70.21, very low certainty), myocardial infarction (2 studies, 322 participants: RR 1.47, 95% CI 0.06 to 34.46; very low certainty) and kidney failure (8 studies, 2370 participants: RR 1.23, 95% CI 1.00 to 1.52, very low certainty). HIF stabilisers may decrease requirements for blood transfusion (7 studies, 1751 participants: RR 0.41, 95% CI 0.28 to 0.59, low certainty). Compared to ESA, HIF stabilisers had uncertain effects on cardiovascular death (6 studies, 1404 participants: RR 3.87, 95% CI 0.43 to 34.55, very low certainty), myocardial infarction (3 studies, 775 participants: RR 2.11, 95% CI 0.24 to 18.90, very low certainty), and kidney failure (2 studies, 492 participants: RR 6.08, 95% CI 1.40 to 26.48, low certainty.
Conclusion: HIF stabilisers have uncertain effects on cardiovascular and kidney outcomes, while decreasing blood transfusions when compared to placebo in people with CKD. HIF stabilisers have uncertain effects compared to ESA.
Patrizia Natale, Research Associate, has completed an MSc in Clinical Epidemiology at the University of Sydney, and a bachelor’s degree in Pharmacy. Patrizia is a researcher at the Centre of Kidney Research at the University of Sydney, and she has experience in Cochrane Systematic Reviews in patients with all stages of CKD (including patients undergoing dialysis and kidney transplant recipients), and in the design and conduct of randomized controlled trials and long-term cohort studies. She has completed the PhD in nephrology and kidney transplantation at the University of Bari, Italy.