Aldosterone receptor antagonism in patients with diabetes and chronic kidney disease: new promises and old problems

Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD), an industry-promoted phase 3, randomized, double-blind, placebo-controlled, multicentre trial investigated the long-term effects on renal and cardiovascular (CV) outcomes of finerenone, a non-steroidal, selective mineralocorticoid receptor antagonist (MRA) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). • The overall population included 5734 eligible patients with a urinary albumin-to-creatinine ratio (UAC) between 30 and 300 mg/g, an estimated glomerular filtration rate (eGFR) of 25 to <60 mL/min/1.73 m2 of body surface area and diabetic retinopathy, or—in the presence of UAC of 300 to 5000 mg/g—an eGFR of 25 to <75 mL/min/1.73 m2 . • When added to standard treatment (including a max dose of a renin-angiotensin system blocker), finerenone (10 mg or 20 mg according to renal function) was shown to be superior to placebo with respect to the primary composite outcome, assessed in a time-to-event analysis, of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.73–0.93; P ¼ 0.001) during a median follow-up of 2.6 years. Finerenone also reduced the incidence of the key secondary composite outcome of death from CV causes, non-fatal myocardial infarction (MI), non-fatal stroke, or hospitalization for heart failure (HF) (HR 0.86, 95% CI 0.75–0.99; P ¼ 0.003). • The incidence of serious adverse events did not differ significantly between finerenone and placebo. However, overall hyperkalaemia-related adverse events were twice as frequent with finerenone as with placebo (18.3% and 9.0%, respectively) and the frequency of hyperkalaemia leading to discontinuation was also higher with finerenone than placebo (2.3% vs. 0.9%).