Mineralocorticoid Receptor-Associated Hypertension and Target Organ Damage: Clinical Relevance for Resistant Hypertension in End Stage Renal Disease

Abstract

Mineralocorticoid receptor (MR) blockade has proven efficacy in the treatment of hypertension and in improving morbidity and mortality in patients with heart failure. The potential importance of mineralocorticoid receptor blockade has grown recently amid the observation that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers do not effectively reduce aldosterone levels in all patients over the long term. To date, research on the role of MR blockade has primarily focused on resistant hypertension, decreasing proteinuria, and potentially preventing disease progression in early stages of chronic kidney disease (CKD). Given the prevalence of co-morbid resistant hypertension and cardiovascular disease in patients with end-stage renal disease (ESRD), however, interest in the role of MR blockade in this patient population has arisen. In this paper, we review the current evidence for using MR blockade in mild-tomoderate and resistant hypertension in patients with normal renal function, CKD, and ESRD. We discuss recent animal and human studies on the role of aldosterone in mediating hypertension as well as vascular and tissue damage. We then review clinical studies on the use of MR blockade in ameliorating aldosterone’s deleterious end organ effects and its applicability to patients with ESRD. Finally, we summarize the evidence to date supporting the safety of MR blockade in patients with ESRD.