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The use of an angiotensin-converting enzyme (ACE) inhibitor prevented the development of microalbuminuria during 3.6 years of treatment of people with type 2 diabetes, according to research reported in the New England Journal of Medicine.1
An increase in albumin in the urine, or microalbuminuria, will develop in about 2% to 5% of people with type 2 diabetes each year. It is one of the earliest signs of kidney disease, a source of considerable morbidity and mortality in these patients. About one-third of those with type 2 diabetes eventually will suffer progressive deterioration of renal function.
Previous evidence has shown that some antihypertensive drugs, including ACE inhibitors and angiotensin receptor blockers (ARBs), reduce the risk of diabetic kidney disease in addition to myocardial infarction, heart failure, and stroke. Weaker evidence suggests calcium-channel blockers (CCBs) might have the same effect.
Whether any of these drugs could help prevent microalbuminuria for those with type 2 diabetes and normal urinary albumin excretion remained unexamined. Thus, the Italian researchers set out to compare the effects on the incidence of microalbuminuria of the ACE inhibitor trandolapril (Mavik, Abbott) (2 mg/day), the non-dihydropyridine CCB verapamil (Isoptin, Abbott) (sustained release, 240 mg/day), both drugs in combination (2 mg trandolapril plus 180 mg/day of verapamil), and placebo. Abbott, which makes trandolapril and verapamil, helped fund the study.
The researchers randomized 1,024 subjects to receive one of the study
treatments. The patients were at least 40 years old and had hypertension and
type 2 diabetes. They had a normal albumin excretion rate of <20 µg/min
in two of three overnight samples and a serum creatinine level 
1.5
mg/dl.
During the mean follow-up of 3.6 years, persistent microalbuminuria developed in 10% of the placebo group, 6% of the trandolapril group (2.1 times better than placebo), 5.7% of the combination therapy group (2.6 times better than placebo), and 11.9% of the verapamil group.
"Our results demonstrate that microalbuminuria can be prevented in type 2 diabetes," the authors conclude. "The apparent advantage of ACE inhibitors over other agents includes a protective effect on the kidney against the development of microalbuminuria, which is a major risk factor for cardiovascular events and death in this population."
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This study corroborates that ACE inhibitors are a reasonable first-line choice for patients with type 2 diabetes and hypertension, says Allan S. Brett, MD, professor of medicine and director of general internal medicine at the University of South Carolina School of Medicine. "It is not the only choice, but certainly a good choice in lowering blood pressure and preventing the onset of the appearance of microalbuminuria."
Brett notes that the benefit of the ACE inhibitor trandolapril over placebo is not exactly huge in absolute numbers—just five percentage points—meaning microalbuminuria was prevented in about 1 in 20 patients during several years of treatment.
Yet Harlan M. Krumholz, MD, MSc, a professor at Yale University School of Medicine, says, "the absolute numbers are pretty impressive," especially given that blood pressure among the groups was close.
Krumholz also says that although it would take many years and a much longer study to investigate clinical outcomes, the results of the study suggest a benefit of using an ACE inhibitor early in hypertensive patients with type 2 diabetes.
"This is about earlier prevention," Krumholz says. "It is
suggesting to doctors, if you're trying to make a choice between medications
that may have an equivalent effect on blood pressure, you may want to go in
the direction of an ACE inhibitor." 
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