ACE inhibitors significantly reduce the risk of diabetic kidney disease


Kidney disease is one of the most serious complications of diabetes.  Reducing its incidence can greatly enhance survival, quality of life and reduce costs of care.  Keeping blood pressure under control is essential to this effort.  NICE guidance recommends ACE inhibitors as a first-line therapy for patients with diabetes and high blood pressure.

However, a number of studies have been published in this area in recent years, such as ADVANCE.  This Cochrane systematic review evaluated the impact of this new evidence on primary prevention of new-onset kidney disease in patients with  diabetes.

Bottom line

In diabetes patients without kidney disease, angiotensin-converting enzyme inhibitors (ACEi) reduced the risk of new onset of microalbuminuria, macroalbuminuria or both when compared to placebo (8 studies, 11,906 patients: RR 0.71, 95% CI 0.56 to 0.89).  This evidence is consistent with current guidance.

Clinical question

  • Patients:  type 1 or type 2 diabetes without kidney disease
  • Interventions:  any antihypertensive agents compared with placebo, no treatment or another antihypertensive agent.  These included ACEi, angiotensin receptor blockers (ARB), calcium channel blockers (CCBs), beta-blockers and diuretics
  • Outcomes:  development of microalbuminuria ormacroalbuminuria, mortality, doubling of serum creatinine, end stage kidney disease and other diabetes-related outcomes.


A comprehensive literature search was carried out, including both MEDLINE and EMBASE, clinical trials registers and hand searching of key journals.

Study selection, study assessment and data extraction were carried out by two blind, independent reviewers.  Individual studies were assessed for their risk of bias according to Cochrane protocols.  In studies that included both participants with and without kidney disease, study authors were contacted for data on individuals with normoalbuminuria at the start of the trial.

The reviewers assessed both clinical and statistical heterogeneity of the individual studies.  Sensitivity analyses were planned to investigate different patient subgroups and the potential impact of bias in individual studies.


26 studies were found, including 33,735 patients who had normoalbuminuria.

  • ACE inhibitors reduced the risk of new onset of microalbuminuria, macroalbuminuria or both when compared to placebo (8 studies, 11,906 patients: RR 0.71, 95% CI 0.56 to 0.89).
  • No significant benefit was found for ARBs versus placebo.
  • ACEi also reduced the risk of mortality compared with placebo (RR 0.84, 95% CI 0.73 to 0.97).
  • ACEi were better than CCBs in studies that conducted a direct comparison.
  • Although ACEi increased the incidence of cough, other adverse events were not statistically significant.


This updated systematic review has several times more data than a previous analysis, and has shown that ACEi reduced the risk of new onset kidney disease by 29% and the risk of death by 16% in people with diabetes.


  • Sensitivity analysis found that a greater treatment effect was found in smaller studies with a higher risk of bias, suggesting that these studies were more prone to bias in favour of treatment.
  • The effects were found to be robust throughout subgroup analysis, including whether or not patients had hypertension orwhich type of diabetes they had.


Lv J, Perkovic V, Foote CV, Craig ME, Craig JC, Strippoli GFM. Antihypertensive agents for preventing diabetic kidney disease. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD004136. DOI: 10.1002/14651858.CD004136.pub3.

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I am an information scientist with an interest in making knowledge from systematic research more accessible to people who need it. This means you. I've been attempting this in the area of Evidence-Based Health Care since 1995. So far the results have been mixed. For some reason we expected busy clinicians to search databases and appraise papers instead of seeing patients. We also expected publishers to make the research freely available to the people who paid for it.. Ha! Hence The National Elf service.

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