Nonsteroidal Mineralocorticoid Receptor Antagonist Eliciting Cardiorenal Protection Is a New Option for Patients with Chronic Kidney Disease

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) protect cardiorenal function by robust anti-inflammatory and antifibrotic functions beyond classical functions of maintaining fluid and electrolyte homeostasis. The application of traditional steroidal MRAs to chronic kidney disease (CKD) has been limited by adverse events, especially when combined with renin-angiotensin system inhibitors, guideline-recommend drugs for CKD patients. Recently, the development of nonsteroidal MRAs gives patients with CKD a promising option. SUMMARY: The discovery of nonsteroidal MRAs is based on the molecular structure of the mineralocorticoid receptor (MR) and differs in structure from spironolactone, a progesterone derivative. The structure of nonsteroidal MRAs determines their more effective and selective inhibition of MR providing patients more benefits with fewer adverse effects than MRAs. Recently, two types of nonsteroidal MRAs, finerenone and esaxerenone, have been authorized for clinical use. We elaborate on the physiological and pathophysiological mechanisms of MR, review the history of MRAs, compare two generations of MRAs, and introduce the forward clinical trials of finerenone and esaxerenone. KEY MESSAGES: Finerenone reduces the cardiovascular and kidney composite outcomes in diabetic patients with CKD eliciting a cardiorenal protection effect. Esaxerenone can effectively reduce blood pressure in hypertensive patients and albuminuria in diabetic patients with CKD. The risk of hyperkalemia is controllable and acceptable through the serum potassium-based dose titrate. Combination therapy with sodium-glucose cotransport-2 inhibition or a new potassium binder may be a safer and more efficient approach.