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Review: ACE inhibitors, but not angiotensin II receptor antagonists, reduce all cause mortality in diabetic nephropathy
  1. Edgar V Lerma, MD, FACP, FASN
  1. University of Illinois at Chicago College of Medicine/ Associates in
 Nephrology, SC
 Chicago, Illinois, USA

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 Q In patients with diabetic nephropathy, what are the effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (AIIRAs)?

    Clinical impact ratings GP/FP/Primary care ★★★★★☆☆ IM/Ambulatory care ★★★★★☆☆ Internal medicine ★★★★★☆☆ Nephrology ★★★★★☆☆ Endocrine ★★★★★★☆


    Embedded ImageData sources:

    Medline (1966 to September 2003), EMBASE/Excerpta Medica (1988 to September 2003), the Cochrane Library, conference proceedings, and contact with experts.

    Embedded ImageStudy selection and assessment:

    randomised controlled trials (RCTs) in any language of ⩾6 months’ duration comparing ACE inhibitors or AIIRAs with placebo, no treatment, or each other in patients with any stage of diabetic nephropathy. Studies were assessed for methodological quality.

    Embedded ImageOutcomes:

    all cause mortality and renal outcomes.


    43 RCTs (follow up range 6–96 mo) met the selection criteria; 36 (4008 patients) compared ACE inhibitors with placebo or no treatment, 4 (3331 patients) compared AIIRAs with placebo or no treatment, and 3 (206 patients) compared ACE inhibitors with AIIRAs. ACE inhibitors, but not AIIRAs, reduced all cause mortality more than placebo or no treatment (table). The table shows the effects of ACE inhibitors and AIIRAs on renal outcomes. ACE inhibitors did not differ from placebo or no treatment for the rate of doubling of serum creatinine levels or of end stage renal disease. Data are lacking on the comparative effects of ACE inhibitors and AIIRAs on mortality and renal outcomes.

    Angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists (AIIRAs) v placebo or no treatment (control)*


    In patients with diabetic nephropathy, angiotensin converting enzyme inhibitors, but not angiotensin II receptor antagonists, reduced all cause mortality compared with placebo.


    Both ACE inhibitors and AIIRAs have been noted for their anti-proteinuric properties.1 However, it is unclear whether ACE inhibitors are more renoprotective than AIIRAs, specifically in patients with diabetic nephropathy; and this is what Strippoli et al attempted to address.

    In this review, the only large randomised trial to show renoprotection associated with ACE inhibitors involved patients with type 1 diabetes.2 On the other hand, the only study to show renoprotection associated with ACE inhibitors in type 2 diabetes is limited by the small number of patients and the fact that the patients did not fully satisfy the criteria for diabetic nephropathy.3 Furthermore, as the authors alluded to, the indirect nature of comparison between ACE inhibitors and AIIRAs, using placebo as comparator, is a major limitation.

    Much heterogeneity existed in the included studies, thus it is quite difficult to make conclusions and actual recommendations based on the data. Certainly, randomised controlled trials that directly compare ACE inhibitors and AIIRAs in patients with diabetic nephropathy are needed to better settle the issues at hand. Until then, the only recommendations that can be derived from current published data are the use of ACE inhibitors in type 1 diabetes with nephropathy2 and the use of ACE inhibitors or AIIRAs in type 2 diabetes with nephropathy.1,4



    • For correspondence: Dr G F Strippoli, University of Sydney, New South Wales, Australia.

    • Sources of funding: Australia-Europe Scholarship; NHMRC Centre for Clinical Research Excellence Grant; Italian Society of Nephrology.