E CHUNG 1,2, R LIN 2, K NEGISHI 3,4, M KOMALA 2
1Centre For Kidney Research, Westmead, Australia, 2Department of Nephrology, Nepean Hospital, Kingswood, Australia, 3Sydney Medical School Nepean, Faculty of Medicine and Health, Charles Perkins Centre Nepean, The University of Sydney, Kingswood, Australia, 4Department of Cardiology, Nepean Hospital, Kingswood, Australia
Aim : To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in dialysis patients.
Background: Dialysis patients are at high risk of cardiovascular disease. The benefits and harms of MRAs on cardiovascular outcomes in dialysis patients have not been recently summarised
Methods: We searched MEDLINE, Embase and CENTRAL through February 2021. Risk of bias was assessed using the Cochrane tool and evidence certainty was evaluated using the GRADE process. Pre-specified outcomes were death, cardiovascular death, hyperkalaemia, serum potassium, hypotension, gynecomastia, myocardial infarction, stroke, worsening heart failure, hospitalisation for cardiovascular cause, left ventricular mass-index, left ventricular ejection fraction and blood pressure.
Results: Fifteen RCTs (1412 participants) were included. MRAs probably reduce the risk of death (10 studies, 1198 participants, relative risk (RR) 0.47 [95% confidence interval 0.32-0.69]; moderate certainty evidence) and cardiovascular death (9 studies, 1150 participants, RR 0.42 [95% CI 0.26-0.69]; moderate certainty evidence) compared to placebo or no treatment. MRA probably increase the risk of gynecomastia (7 studies, 957 participants, RR 5.61 [95% CI 2.07-15.22]; moderate certainty evidence). There was clinically negligible increase in end-of-treatment serum potassium (8 studies, 913 participants, MD 0.21 mmol/L [95% CI 0.06 – 0.35], very low certainty evidence) and MRA may increase risk of hyperkalaemia (11 studies, 1244 participants, RR 1.43 [1.00, 2.03], low certainty evidence).
Conclusion:MRAs probably reduce the risk of death in dialysis patients but probably increase the risk of gynecomastia. MRA may cause a small increase in serum potassium but inconclusive on the risk of hyperkalemia thus further investigation is recommended.
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.