title: Mineralocorticoid receptor antagonist for renal protection.
abstract: The renin-angiotensin system (RAS) plays an important role in the pathophysiology of cardiovascular and renal diseases. In chronic kidney disease (CKD), blockade of RAS by angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) has been shown to reduce proteinuria and retard the progression of renal function deterioration. However, aldosterone, another key hormone of the RAS, is not directly targeted by ACEI or ARB. Hyperaldosteronism, apart from promoting sodium and fluid retention, causes inflammation and fibrosis in the heart and kidney. Studies have shown that although plasma aldosterone level shows an initial decrease following ACEI or ARB treatment, it returns to pretreatment level or even increases paradoxically after prolonged treatment. This "aldosterone breakthrough" forms the basis of adding mineralocorticoid receptor (MR) antagonist on top of ACEI or ARB for renal protection. New insights into the pathophysiological role of aldosterone in CKD further expands its potential indications, and there was a growing body of evidence in the past 10 years, which showed a substantial antiproteinuric effect and possibly a considerable renoprotective effect of MR antagonist. Since aldosterone does not act on the efferent glomerular arteriole and has no effect on intraglomerular hemodynamics, the very fact that MR antagonist ameliorates proteinuria sheds light on the physiology of glomerular permeability barrier. This review summarizes the data regarding the theoretical benefit as well as clinical use of MR antagonist in renal diseases.
authors.affiliation: Division of Nephrology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Terry King-Wing
authors.initials: TK
authors.lastname: Ma
authors.forename: Cheuk-Chun
authors.initials: CC
authors.lastname: Szeto
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000077545:Eplerenone; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone