Provenzano, Michele; Jongs, Niels; Vart, Priya; Stefánsson, Bergur V; Chertow, Glenn M; Langkilde, Anna Maria; McMurray, John JV; ... DAPA-CKD Trial Committees and Investigators; + view all Provenzano, Michele; Jongs, Niels; Vart, Priya; Stefánsson, Bergur V; Chertow, Glenn M; Langkilde, Anna Maria; McMurray, John JV; Correa-Rotter, Ricardo; Rossing, Peter; Sjöström, C David; Toto, Robert D; Wheeler, David C; Heerspink, Hiddo JL; DAPA-CKD Trial Committees and Investigators; - view fewer (2022) The Kidney Protective Effects of the Sodium–Glucose Cotransporter-2 Inhibitor, Dapagliflozin, Are Present in Patients With CKD Treated With Mineralocorticoid Receptor Antagonists. Kidney International Reports , 7 (3) pp. 436-443. 10.1016/j.ekir.2021.12.013.

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Abstract

Introduction: Mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of kidney failure in chronic kidney disease (CKD). We performed an analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial by baseline conventional MRA (spironolactone and eplerenone) prescription. Methods: Participants with CKD (estimated glomerular filtration rate [eGFR] 25-75 ml/min per 1.73 m2; urinary albumin-to-creatinine ratio 200-500 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or kidney or cardiovascular (CV) death. A prespecified kidney-specific secondary outcome was as the primary outcome but without CV death. Hyperkalemia (serum potassium ≥6.0 mmol/l) was an exploratory end point. Time-to-event analyses (proportional hazards [Cox] regression) assessed dapagliflozin versus placebo in patient subgroups defined by baseline conventional MRA use. Results: A total of 229 of 4304 DAPA-CKD participants (5.3%) were receiving conventional MRAs at baseline (dapagliflozin n = 109, placebo n = 120). The effect of dapagliflozin on the primary outcome was consistent in participants prescribed (hazard ratio [HR] 0.76, 95% CI 0.40-1.47) and not prescribed (HR 0.60, 95% CI 0.50-0.72, P-interaction = 0.59) MRAs. This consistency was maintained for the kidney-specific outcome. The effect of dapagliflozin on hyperkalemia (HR 0.87, 95% CI 0.70-1.09) was consistent among those prescribed (HR 0.94, 95% CI 0.41-2.20) and not prescribed (HR 0.87, 95% CI 0.69-1.10, P-interaction = 0.96) MRAs. Adverse events (AEs) leading to discontinuation and serious AEs were similar between treatment groups, regardless of baseline MRA prescription. Conclusion: Dapagliflozin was similarly safe and efficacious in reducing major adverse kidney outcomes in participants with CKD who were or were not prescribed MRAs at baseline.

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