Targeting the aldosterone-mineralocorticoid receptor pathway in cardiovascular-kidney-metabolic syndrome

The concept of cardiovascular-kidney-metabolic (CKM) syndrome integrates cardiovascular, kidney and metabolic disorders into a single pathophysiological continuum characterized by chronic inflammation, oxidative stress, fibrosis and progressive organ dysfunction. A central driver of CKM syndrome progression is inappropriate activation of the aldosterone-mineralocorticoid receptor (MR) pathway, which promotes adverse remodelling of the heart, kidney, vasculature, adipose tissue, liver and pancreas. Steroidal MR antagonists (MRAs) and non-steroidal MRAs mitigate maladaptive MR signalling and improve cardiorenal outcomes. Compared with steroidal MRAs, non-steroidal MRAs such as finerenone provide enhanced tissue selectivity and favourable safety profiles. Finerenone has been shown to reduce cardiovascular and renal events in patients with chronic kidney disease (CKD) and in patients with heart failure. Aldosterone synthase inhibitors represent a complementary approach that suppresses aldosterone production upstream of MR activation and has shown promising results in resistant hypertension and CKD. Preclinical and clinical data indicate that combined strategies targeting the aldosterone-MR axis can attenuate cardiorenal remodelling, insulin resistance and organ injury, offering a comprehensive therapeutic approach. Ongoing trials will clarify the efficacy of these combined therapies in non-diabetic CKD, resistant hypertension and broader CKM syndrome populations. Overall, targeting the aldosterone-MR pathway represents a central strategy to reduce organ dysfunction, improve metabolic homeostasis and limit progression of CKM syndrome.