Aldosterone and Aldosterone Modulation in Cardio-Kidney Diseases

Abstract

Chronic renin-angiotensin-aldosterone system activation and excess aldosterone exert detrimental effects on the heart and the kidneys via contributing to inflammation, fibrosis, and dysfunction in the myocardium, vasculature, and the kidneys. These effects are purported to be through genomic mineralocorticoid receptor (MR)–mediated, nongenomic MR-dependent, and nongenomic non-MR dependent actions. Steroidal and nonsteroidal mineralocorticoid receptor antagonists (MRA) counteract the effects of aldosterone in heart failure (HF) and in chronic kidney disease (CKD), blocking, at least partially, both genomic and nongenomic MR-mediated effects. Because both hyperkalemia and excess aldosterone are associated with progression of CKD and HF, and MRA therapy is associated with elevations in aldosterone levels, patients on MRA therapy may remain at a high residual risk for poor outcomes even on MRA therapy. Although observational studies and trials suggest compensatory neurohormonal activation in patients treated with renin-angiotensin-aldosterone system inhibitors, its potential association with worse outcomes and clinical significance is complex and context-dependent. Further studies are needed to better clarify the clinical implications of these biological effects in patients with cardio-kidney diseases. Partial agonists of the MR and directly attenuating aldosterone production using selective aldosterone synthase inhibitors is an emerging approach for patients with HF, CKD, and uncontrolled and resistant arterial hypertension that requires prospective trials. This review sought to describe the role of aldosterone in HF and CKD and the role of steroidal and nonsteroidal MRA, partial agonists of the MR, and aldosterone synthase inhibitors in cardio-kidney diseases.