Several decades ago, large studies of patients with type 1 diabetes demonstrated a dangerous association between microalbuminuria and later progression to overt proteinuria. Use of angiotensin-converting enzyme (ACE) inhibitors has been advocated for patients with microalbuminuria to decrease the progression of diabetic nephropathy. More recent studies, however, have not confirmed a relentless progression of diabetic renal disease in patients with microalbuminuria. In a substantial portion of cases, microalbuminuria stabilizes and, in some instances, even reverses. Perkins and colleagues followed a population of patients who had type 1 diabetes with microalbuminuria over an eight-year period to determine which clinical indicators were associated with a decrease in urinary albumin excretion.
The authors enrolled every other consecutive patient 15 to 44 years of age seen over a one-year period at a diabetes research center. Those with microalbuminuria (i.e., albumin excretion rate of 30 to 299 mcg per minute) that persisted over the first two years of the study were then followed for an additional six years. An average of three urine samples were obtained for each two-year follow-up interval. Regression of microalbuminuria was defined as a 50-percent reduction in albumin excretion over a two-year period. Of the initial 312 patients enrolled and the additional 109 patients who developed microalbuminuria later in the study, follow-up was lost in 8 percent of cases.
During the six additional years of follow-up, overt proteinuria (i.e., albumin excretion rate greater than 300 mcg per minute) developed in 15 percent of patients with microalbuminuria. Regression of microalbuminuria occurred in 58 percent of patients and decreased enough to qualify as normal albumin excretion (i.e., less than 30 mcg per minute) in 40 percent of patients.
Use of ACE inhibitors was not associated with regression. In fact, their use was more common in patients whose albumin excretion rate failed to improve. Clinical factors associated with regression of microalbuminuria include younger age, shorter duration of microalbuminuria, lower systolic blood pressure, lower level of hemoglobin A1c, and less hyperlipidemia. Patients with the best control of modifiable risk factors (i.e., systolic pressure less than 115 mm Hg, cholesterol level less than 198 mg per dL [5.12 mmol per L], triglyceride level less than 145 mg per dL [1.64 mmol per L], and hemoglobin A1c level less than 8 percent) were three times more likely to have regression.
The authors conclude that microalbuminuria in patients with type 1 diabetes often regresses, and that better control of blood pressure, lipids, and hemoglobin A1c is associated with decreased urinary albumin excretion.
editor's note: Although this is a prospective, well-designed study, it is important to remember that it is not randomized. The lack of a beneficial effect on microalbuminuria with the use of ACE inhibitors may have more to do with the higher likelihood of using these agents in sicker patients with diabetes (who would be more likely to have progressive nephropathy), rather than any failure of ACE inhibitors themselves to provide protection to the diabetic kidney. This study confirms that better control of risk factors for vascular diseases often occurring in patients with diabetes (such as hypertension, hyperlipidemia, hyperglycemia) helps to prevent the progression of nephropathic changes.—B.Z.