Finerenone: a new approach to the treatment of chronic kidney disease in patients with type 2 diabetes

Chronic kidney disease (CKD) represents one of the leading causes of morbidity and mortality worldwide, being diabetes its first cause. Besides the strict management of risk factors (i.e. hyperglycemia, hypertension and dyslipidemia), several pharmacological strategies aiming at reducing the progression of CKD, including ACE-inhibitors, have been proposed. Finerenone is the first non-steroidal selective mineralocorticoid receptor antagonist (ns-MRA) drug developed for the treatment of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Its properties include a high selectivity for MRs with a lower incidence of side effects such as gynecomastia and hyperkalemia with respect to older steroidal MRAs. In addition, a significant reduction of fibrosis, inflammation and hypertrophy both on myocardium and kidney has been observed. At present, several studies demonstrating the efficacy and safety of finerenone on clinical outcomes have been published. In the phase III studies, FIDELIO-DKD and FIGARO-DKD, finerenone significantly reduced the combined primary endpoints (progression of chronic kidney disease, renal failure or renal death for renal outcomes, and cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure for cardiovascular outcomes) when compared to placebo and added to the standard of care. A pooled-analysis (FIDELITY) performed on a prespecified pool of patients derived from the combination of the previous two studies confirmed the ability of finerenone to significantly reduce both the incidence or progression of DKD and cardiovascular events. A higher incidence of hyperkalemia in patients treated with finerenone compared to placebo was confirmed. However, the incidence of adverse events with clinical impact was low, and only 1,7% of finerenone-treated patients versus 0,6% of placebo-treated patients discontinued treatment during a 3-year follow-up. Finerenone broadly demonstrates an effective renal and cardiovascular protective capacity in patients with T2D and DKD in the presence of good safety in its use. KEY WORDS: diabetic nephropathy; cardiovascular disease; end stage renal disease; type 2 diabetes.