Cardiorenal benefits of mineralocorticoid antagonists in CKD and type2 diabetes : Lessons from the FIGARO-DKD trial.

Abstract

Diabetic kidney disease (DKD) develops in almost half of all patients with diabetes and is the most common cause of chronic kidney disease (CKD) worldwide. Despite the high risk of chronic renal failure in these patients, only few therapeutic strategies are available. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with DKD was established years ago and remains the hallmark of therapy. The past 2years have seen adramatic change in our therapeutic arsenal for CKD. Sodium-glucose co-transporter‑2 inhibitors (SGLT2s) have been successfully introduced for the treatment of CKD. Afurther addition is anovel compound antagonizing the activation of the mineralocorticoid receptor: finerenone. Finerenone reduces albuminuria and surrogate markers of cardiovascular disease in patients who are already on optimal therapy. In the past, treatment with other mineralocorticoid receptor antagonists was hampered by asignificantly increased risk of hyperkalemia. Finerenone had amuch smaller effect on hyperkalemia. Together with areduced effect on blood pressure and no signs of gynecomastia, this therapeutic strategy had amore specific anti-inflammatory effect and a smaller effect on the volume/electrolyte axis. In the FIDELIO-DKD study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of DKD and the incidence of cardiovascular events, with arelatively safe adverse event profile. In this article, we summarize the available evidence on the cardioprotective and nephroprotective effects of finerenone and analyze the molecular mechanisms involved. In addition, we discuss the potential future role of mineralocorticoid receptor inhibition in the treatment of patients with diabetic CKD.