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 t he decline in renal function in diabetic patients with microalbuminuri a. However, no data are available on the use of ACE inhibitors to prev ent the decrease in renal function in normotensive, normoalbuminuric p atients with type 2 diabetes. Objective: To evaluate the effect of pro longed ACE inhibition on renal function and albuminuria in patients wi th type 2 diabetes. Design: Randomized, double-blind, placebo-controll ed trial with 6-year follow-up. Setting: Eight outpatient clinics coor dinated 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 al buminuria (albumin excretion less than or equal to 30 mg/24 h). Interv ention: Enalapril, 10 mg/d, or placebo. Measurements: Degree of albumi nuria at 24 hours, creatinine clearance, blood pressure, and hemoglobi n A(1c) 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 ye ars. 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 far enalapri l compared with placebo). Transition to microalbuminuria occurred in 1 5 of 79 (19%) placebo recipients and 5 of 77 (6.5%) enalapril recipien ts. 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 enalapri l recipients and from 1.81 +/- 0.15 mL/s to 1.57 +/- 0.17 mL/s (mean d ecrease, 0.04 mL/s per year) in placebo recipients (P = 0.040). Hemogl obin A(1c) values decreased modestly in both groups. Mean blood pressu re remained normal (<107 mm Hg) in all patients. Conclusions: Enalapri l attenuated the decline in renal function and reduced the extent of a lbuminuria in normotensive, normoalbuminuric patients with type 2 diab etes, Further research is needed to determine whether this treatment f orestalls the development of overt nephropathy.