Angiotensin converting enzyme inhibitors in normotensive diabetic patients with microalbuminuria

Abstract

To examine whether the progression of early diabetic renal disease to end-stage renal failure may be slowed by the use of angiotensin converting enzyme inhibitors for reasons other than their antihypertensive properties, so that they have value in the treatment of normotensive diabetics with microalbuminuria. MEDLINE was searched for English language reviews and randomised controlled trials. Personal reference lists, and reference lists of retrieved studies were also used. Randomised controlled trials with separate identifiable results for initially normotensive diabetic patients, who received angiotensin converting enzyme inhibitors for at least one year and were compared with controls. Meta-analyses were performed on the results of 11 randomised controlled trials with a variety of patient inclusion and exclusion criteria. Albumin excretion rate fell for patients on angiotensin converting enzyme inhibition in 10 of the 11 studies but did so for only two of the 11 groups on placebo. Treatment provided a significant reduction in albumin excretion rate in both insulin dependent diabetes mellitus and non insulin dependent diabetes mellitus. Treatment with either captopril, enalapril or lisinopril reduced albumin excretion rate in comparison with control patients. A greater lowering of blood pressure was experienced by initially normotensive patients in the angiotensin converting enzyme inhibitor than in the placebo group. Pooled end-of-study mean blood pressures for the treated group were significantly lower than for the untreated group, although this was not so for all individual studies. The apparent (treatment - placebo) 'effect' on systolic and diastolic pressures had a larger standard error for longer lasting studies. Average haemoglobin fell a little in the treated patients and rose in the controls but neither this nor the difference in changes in glomerular filtration rate reached statistical significance. Inhibition of angiotensin converting enzyme can arrest or reduce the albumin excretion rate in microalbuminuric normotensive diabetics, as well as reduce or prevent an increase in blood pressure. But, given the drop in blood pressure in patients on angiotensin converting enzyme inhibitors, it is not possible to be certain that the reduction of albumin excretion rate is due to a separate renal effect. A direct link with postponement of end-stage renal failure has not been demonstrated. There appear to be no substantial side effects.