Dr Edmund Chung1, Prof Suetonia Palmer2, Prof Giovanni Strippoli3,4,5

1Cochrane Kidney and Transplant, Centre For Kidney Research, Westmead, Australia, 2University of Otago, Christchurch, New Zealand, 3University of Bari, Bari, Italy, 4Cochrane Kidney and Transplant, Centre for Kidney Research, Westmead, Australia, 5School of Public Health, University of Sydney, Camperdown, Australia

Aim: To compare the efficacy and safety of erythropoiesis-stimulating agents (ESAs) against each other to treat anaemia in adults with chronic kidney disease (CKD).

Background: Several ESAs are available to treat CKD-related anaemia but whether they have different effects on patient outcomes compared to placebo or each other is uncertain.

Methods:  We did a Cochrane review with network meta-analysis. We searched the Cochrane Kidney and Transplant Register until January 2021 for randomised controlled trials evaluating ESAs in adults with CKD. Risk of bias was assessed using the Cochrane tool. Data synthesis was performed using random effects meta-analysis. We assessed evidence certainty for the primary outcomes (blood transfusions and all-cause death) using GRADE. We also assessed secondary outcomes (fatigue, breathlessness, cardiovascular events and kidney failure).

Results: 117 studies (n=24,998) proved eligible. The effects on preventing blood transfusion or all-cause death were uncertain for any ESA compared to another ESA, in low to very low-certainty evidence. Compared to placebo for preventing blood transfusion, epoetin alfa (odds ratio 0.28, 95% confidence interval 0.13-0.61, low-certainty evidence), epoetin beta (0.19, 0.08-0.47, low-certainty evidence), and darbepoetin alfa (0.27, 0.11-0.67, moderate-certainty evidence) were superior, though effects for methoxy polyethylene glycol-epoetin beta, biosimilar epoetin and biosimilar darbepoetin alfa were uncertain, in very low-certainty evidence. Compared to placebo for all-cause cause death, darbepoetin alfa probably had similar effects, in moderate-certainty evidence and other ESAs had uncertain effects, in low to very low-certainty evidence. It was uncertain whether ESAs had different effects on cardiovascular events, kidney failure, and breathlessness compared to another ESA. Data for fatigue were absent.

Conclusions: Different ESAs have similar or uncertain effects on blood transfusion, all-cause death, cardiovascular events, and breathlessness.


Edmund is an adult nephrologist with a strong interest in glomerulonephritis and identifying strategies to limit the progression of chronic kidney disease. He completed a BMed MD at UNSW, MMed (Clin Epi) at The University of Sydney, and has worked with the Cochrane Kidney and Transplant Group on multiple systematic reviews to apply best evidence-based practice to his patients. He is currently undertaking a PhD with Prof Steven Alexander at the Centre for Kidney Research on regulatory T cells and other immunotherapies in primary membranous nephropathy with the goal of translating novel efficacious and less toxic treatments into clinical care.

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