Oh! What all adverse effects for excess aldosterone!

Mineralocorticoid receptor antagonists are useful for the management of heart failure. But what all are the adverse effects of excess aldosterone in the system? Let us have a look. Aldosterone can have its effect through genomic and non genomic pathways. In genomic pathway, the effect is on the nucleus causing transcription after binding to mineralocorticoid receptors. In non genomic pathway, mineralocorticoid receptors are involved in transcription independent regulation of cellular functions like oxidative metabolism, electrolyte balance, inflammation and apoptosis. Mineralocorticoid receptor antagonists can counteract the effects of aldosterone at least partially on both genomic and nongenomic effects. But receptor antagonism and associated hyperkalemia cause increase in aldosterone levels. This may exacerbate non mineralocorticoid receptor dependent effects of aldosterone [1].

Those with primary hyperaldosteronism have higher inflammation, fibrosis, atrial remodeling, left ventricular hypertrophy, both ventricular systolic and diastolic dysfunction, vascular remodeling and atherosclerosis. They are at a higher risk of myocardial infarction, atrial fibrillation, stroke and diabetes. Excess aldosterone can cause progressive renal fibrosis, vascular disease and podocyte injury. There can be progressive decline in renal function and albuminuria. There is some data to suggest that mineralocorticoid receptor antagonist therapy in primary aldosteronism is associated with higher risk of incident cardiometabolic events and death independent of blood pressure control, compared to those with essential hypertension. Careful titration of mineralocorticoid receptor antagonist therapy to raise renin may reduce this excess risk [2]. Role of aldosterone synthesis inhibitors have to investigated further in this scenario.

References

1. Fioretti F, Testani JM, Tio MC, Pitt B, Butler J. Aldosterone and Aldosterone Modulation in Cardio-Kidney Diseases. J Am Coll Cardiol. 2025 Aug 5;86(5):354-373. doi: 10.1016/j.jacc.2025.06.012. PMID: 40738563.
2. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study. Lancet Diabetes Endocrinol. 2018 Jan;6(1):51-59. doi: 10.1016/S2213-8587(17)30367-4. Epub 2017 Nov 9. PMID: 29129576; PMCID: PMC5953512.