Journal
KIDNEY INTERNATIONAL
Volume 66, Issue 1, Pages 1-9Publisher
ELSEVIER SCIENCE INC
DOI: 10.1111/j.1523-1755.2004.00701.x
Keywords
blood vessels; diabetes; eplerenone; hypertension; kidney; renoprotection; renal vasculature
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Funding
- NCRR NIH HHS [M01RR02636] Funding Source: Medline
- NHLBI NIH HHS [5P50HL55000, T32HL07609] Funding Source: Medline
- NIDDK NIH HHS [1R01DK5466804] Funding Source: Medline
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Background. The renin-angiotensin-aldosterone system (RAAS) contributes to hypertension and nephropathy. Until recently, aldosterone either has not been considered or has been considered a relatively minor component of the process - a contribution that could be negated with angiotensin-converting enzyme (ACE) inhibition or angiotensin receptor blockade. Methods. A Medline search was performed to identify relevant literature describing the role of aldosterone in the pathogenesis of renal dysfunction. Results. Growing evidence from experimental and clinical studies indicates that increased aldosterone is an independent contributor to small- and medium-sized arterial injury and nephropathy. Excess mineralocorticoid receptor stimulation of local and systemic origin promotes target organ dysfunction, vascular injury, and fibrosis, independent of the effects of other elements of the RAAS. Blockade of the RAAS with ACE inhibition or angiotensin receptor blockade often does not confer optimal protection from the effects of mineralocorticoids on small- and medium-sized blood vessels. Recent preliminary data from clinical studies indicate that aldosterone blockade protects the kidneys, sharply decreases proteinuria, beyond the activities of ACE inhibition or angiotensin receptor blockade and independent of beneficial blood pressure effects, and can protect patients from vascular injury associated with diabetes mellitus and hypertension. Conclusion. Aldosterone blockade with the selective aldosterone blocker eplerenone, in combination with other RAAS inhibitors, is probably renoprotective and should be considered as a component of the treatment regimens of diabetic and hypertensive patients at risk for renal or cardiovascular disease expression. A high priority should be placed on developing the randomized, controlled trials required to establish that role.
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