Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus. A randomized, controlled trial.

BACKGROUND

Angiotensin-converting enzyme (ACE) inhibitors attenuate the decline in renal function in diabetic patients with microalbuminuria. However, no data are available on the use of ACE inhibitors to prevent the decrease in renal function in normotensive, normoalbuminuric patients with type 2 diabetes.

OBJECTIVE

To evaluate the effect of prolonged ACE inhibition on renal function and albuminuria in patients with type 2 diabetes.

DESIGN

Randomized, double-blind, placebo-controlled trial with 6-year follow-up.

SETTING

Eight outpatient clinics coordinated by a department of medicine in a university hospital.

PATIENTS

156 patients in whom type 2 diabetes was diagnosed after 40 years of age who had a baseline mean blood pressure less than 107 mm Hg and albuminuria (albumin excretion < or = 30 mg/24 h).

INTERVENTION

Enalapril, 10 mg/d, or placebo.

MEASUREMENTS

Degree of albuminuria at 24 hours, creatinine clearance, blood pressure, and hemoglobin A1c values.

RESULTS

Enalapril therapy decreased albumin excretion from a mean +/- SD of 11.6 +/- 7 mg/24 h to 9.7 +/- 6 mg/24 h at 2 years. This was followed by a gradual increase to 15.8 +/- 8 mg/24 h at 6 years. In the placebo group, albumin excretion increased from 10.8 +/- 8 mg/24 h to 26.5 +/- 10 mg/24 h at 6 years (P = 0.001 for enalapril compared with placebo). Transition to microalbuminuria occurred in 15 of 79 (19%) placebo recipients and 5 of 77 (6.5%) enalapril recipients. Enalapril treatment resulted in an absolute risk reduction of 12.5% (95% CI, 2% to 23%; P = 0.042) for development of microalbuminuria. After 6 years, creatinine clearance decreased from 1.78 +/- 0.13 mL/s to 1.63 +/- 0.12 mL/s (mean decrease, 0.025 mL/s per year) in enalapril recipients and from 1.81 +/- 0.15 mL/s to 1.57 +/- 0.17 mL/s (mean decrease, 0.04 mL/s per year) in placebo recipients (P = 0.040). Hemoglobin A1c values decreased modestly in both groups. Mean blood pressure remained normal (< 107 mm Hg) in all patients.

CONCLUSIONS

Enalapril attenuated the decline in renal function and reduced the extent of albuminuria in normotensive, normoalbuminuric patients with type 2 diabetes. Further research is needed to determine whether this treatment forestalls the development of overt nephropathy.