Abstract
This commentary discusses the findings and profound clinical implications of a prespecified analysis of renal outcomes performed by Mann et al. in the large ONTARGET study. This study assessed the effects of the angiotensin-converting-enzyme (ACE) inhibitor ramipril and the angiotensin receptor blocker (ARB) telmisartan, separately and in combination, in patients aged at least 55 years who had established vascular disease or diabetes with organ damage. Mann et al. demonstrated that, in contrast to monotherapy with either drug, the combination of an ACE inhibitor and an ARB worsens all major renal outcomes with the exception of proteinuria. This commentary recommends that combination therapy with an ACE inhibitor and an ARB to retard progression of renal disease should be avoided in patients with proteinuria lower than 1 g per day. The utility of dual RAS blockade regimens comprising an ACE inhibitor and a direct renin inhibitor, or an ACE inhibitor or ARB plus an aldosterone blocker, remains to be determined and constitutes a high priority subject for future clinical investigation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Lewis EJ et al. (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy: the Collaborative Study Group. N Engl J Med 329: 1456–1462
De Jong PE et al. (1999) Renoprotective therapy: titration against urinary protein excretion. Lancet 354: 352–353
De Zeeuw D et al. (2004) Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 110: 921–927
Nakao N et al. (2003) Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 361: 117–124
Wolf G and Ritz E (2005) Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. Kidney Int 67: 799–812
Mann JFE et al. (2008) Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind controlled trial. Lancet 372: 547–553
Fisher ND and Hollenberg NK (2005) Renin inhibition: what are the therapeutic opportunities? J Am Soc Nephrol 16: 592–599
Epstein M (2006) Aldosterone blockade: an emerging strategy for abrogating progressive renal disease. Am J Med 119: 912–919
ONTARGET investigators (2008) Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 358: 1547–1559
Author information
Authors and Affiliations
Ethics declarations
Competing interests
The author has declared associations with the following companies: Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline and Lux Biosciences, for all of which he is a consultant.
Rights and permissions
About this article
Cite this article
Epstein, M. Re-examining RAS-blocking treatment regimens for abrogating progression of chronic kidney disease. Nat Rev Nephrol 5, 12–13 (2009). https://doi.org/10.1038/ncpneph0980
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ncpneph0980
This article is cited by
-
The RAAS in the pathogenesis and treatment of diabetic nephropathy
Nature Reviews Nephrology (2010)
-
Is the ONTARGET renal substudy actually off target?
Nature Reviews Nephrology (2009)
-
The intracellular renin-angiotensin system in the heart
Current Hypertension Reports (2009)