A body of evidence suggests that overactivation of the mineralocorticoid receptor (MR) contributes to chronic kidney disease (CKD) progression, indicating that antagonism of this receptor could provide therapeutic benefit. Findings from the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELO-DKD) trial, first presented at the American Society of Nephrology’s 2020 annual meeting, now demonstrate that the selective nonsteroidal MR antagonist, finerenone, lowers the risk of CKD progression and cardiovascular events in patients with advanced CKD and type 2 diabetes mellitus (T2DM). “In this phase III study of 5,734 patients we show that finerenone protects both the heart and the kidneys,” explains Rajiv Agarwal — a researcher involved in the study. “It also reduced albuminuria by >30% at 4 months, had minimal effects on blood pressure and had no effect on glycaemia.”
This multicentre study included adult patients with advanced CKD and T2DM who were treated with an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker at the maximum dose that did not cause unacceptable adverse events. The study design included a run-in period, during which these background medical therapies were adjusted, after which eligible patients were randomly assigned in a 1:1 ratio to receive oral finerenone or placebo. After a median follow-up of 2.6 years, the incidence of the primary composite outcome of kidney failure, a sustained decrease of at least 40% in estimated glomerular filtration rate (eGFR) from baseline, or death from renal causes, was significantly lower in the finerenone group than in the placebo group (504 patients (17.8%) and 600 patients (21.1%), respectively; HR 0.82; 95% CI 0.73–0.93; P = 0.001). The incidence of the key secondary outcome — a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure — was also significantly lower in the finerenone group than in the placebo group (occurring in 367 patients (13.0%) and 420 patients (14.8%), respectively; HR 0.86; 95% CI 0.75–0.99; P = 0.03). Of note, the researchers report that despite a higher overall risk of hyperkalaemia among patients on finerenone than placebo, discontinuation of the trial regimen owing to hyperkalaemia was infrequent. “Permanent discontinuation rates of the drug attributable to hyperkalaemia were 2.3% among patients on finerenone compared to 0.9% with placebo,” says Agarwal. “In other words, one would need to treat 71 patients with finerenone before one stopped the drug due to hyperkalaemia whereas, by comparison, one would need to treat just 29 patients before one avoided the kidney failure outcome as defined in this trial.”
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