RAAS escape: a real clinical entity that may be important in the progression of cardiovascular and renal disease.
Interruption of the renin-angiotensin-aldosterone system (RAAS) at different levels is target-organ protective in several disease states; however, complete blockade is unlikely to be achieved due to escape mechanisms whenever blockade is attempted, incomplete knowledge of the role of all elements of the RAAS, and lack of pharmacotherapy against some elements that have been shown to contribute to disease states. Aldosterone has been overlooked as a mediator of RAAS escape and a key factor in target-organ injury despite the use of available RAAS blockers. Aldosterone is thought to play a role in the development of hypertension, alteration in vascular structure, vascular smooth muscle hypertrophy, endothelial dysfunction, structural renal injury, proteinuria, left ventricular remodeling, collagen synthesis, and myocardial fibrosis. Aldosterone receptor antagonists have been shown to antagonize all these effects in experimental models. Clinical trials with aldosterone antagonists showed an improvement in survival and left ventricular mass index in patients with congestive heart failure, and a reduction in urinary protein excretion and left ventricular mass index in patients with type 2 diabetes and early nephropathy who developed aldosterone synthesis escape. Consequently, aldosterone receptor antagonists may have specific benefits for reducing target-organ injury, particularly if there is evidence of RAAS escape.
Lakkis
Jay
J
Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, 22 South Greene Street, Suite N3W143, Baltimore, MD 21201, USA.
Lu
Wei X
WX
Weir
Matthew R
MR
D000450:Aldosterone / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D000077545:Eplerenone; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D000451:Mineralocorticoid Receptor Antagonists; D012084:Renin-Angiotensin System / Q000502:physiology*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone