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Renal aspirin: will all patients with chronic kidney disease one day take spironolactone?

Nature Clinical Practice Nephrology volume 5, pages 74–75 (2009)Cite this article

Over the past two decades, aldosterone has emerged as a key agent in the pathophysiology of congestive heart failure and, more recently, progressive kidney dysfunction.1 In addition to its effects of promoting sodium retention (and potassium excretion) in epithelial tissues, aldosterone activates mineralocorticoid receptors in the nonepithelial tissues of the heart, kidney, and peripheral vasculature to foster inflammation and fibrosis. As these nonepithelial routes of kidney injury have been uncovered, so too has the remarkable efficacy of mineralocorticoid receptor blockade in countering a variety of renal insults. The results of recent animal and human studies of aldosterone blockade in various kidney diseases prompt speculation that low doses of spironolactone, an inexpensive, generic medication with few and easily recognizable adverse effects, could become a staple therapy for all patients with chronic kidney disease (CKD).

Treatment of diabetic and hypertensive kidney disease, the two leading causes of CKD, relies heavily on blockade of the renin–angiotensin–aldosterone system (RAAS) with angiotensin-converting-enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs). In clinical trials of ACEIs and ARBs, aldosterone levels—after an initial decline—increase in 30–50% of patients during the first year of therapy. This 'aldosterone breakthrough' might increase the risks of proteinuria, a decline in glomerular filtration rate (GFR), and development of left ventricular hypertrophy.2 Patients with CKD who do not respond to ACEIs and/or ARBs—as indicated by persistent proteinuria, refractory hypertension, and declining GFR—could benefit from an additional level of RAAS blockade achieved by targeting aldosterone. Indeed, a growing body of evidence suggests that, when added to conventional RAAS blockers, mineralocorticoid receptor blockers such as spironolactone and eplerenone yield up to 50% reductions in proteinuria.3 These effects, moreover, are achieved with relatively low doses of drug (e.g. 12.5–25.0 mg/day spironolactone), which are generally insufficient to cause diuresis or a substantial drop in blood pressure.

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Authors and Affiliations

  1. AV Kshirsagar is Associate Professor of Medicine and PJ Klemmer is Professor of Medicine in the Department of Medicine, Division of Nephrology and Hypertension, AS Bomback is the Doc J Thurston III Fellow, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.,

    Andrew S Bomback, Abhijit V Kshirsagar & Philip J Klemmer

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  1. Andrew S Bomback
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  2. Abhijit V Kshirsagar
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  3. Philip J Klemmer
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Correspondence to Andrew S Bomback.

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Bomback, A., Kshirsagar, A. & Klemmer, P. Renal aspirin: will all patients with chronic kidney disease one day take spironolactone?. Nat Rev Nephrol 5, 74–75 (2009). https://doi.org/10.1038/ncpneph1004

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