Renoprotective effect of the angiotensin-receptor antagonist irbesartan inpatients with nephropathy due to type 2 diabetes

Background It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capac ity to lower the systemic blood pressure. Methods We randomly assigned 1715 hypertensive patients with nephropathy du e to type 2 diabetes to treatment with irbesartan ( 300 mg daily), amlodipi ne (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line rum creatinine c oncentration, the development of endstage renal disease, or death from any cause. We also compared them with regard to the time to a secondary cardiov ascular composite end point. Results The mean duration of follow-up was 2.6 years. Treatment with irbesa rtan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P= 0.02) and 23 percent lower than that in the amlodipine group ( P= 0.006). The risk of a doubling of the serum concentration was 33 percent lower in the irbesartan group th an in the placebo group ( P= 0.003) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001). Treatment with irbesartan wa s associated with a relative risk of end-stage renal disease that was 23 pe rcent lower than that in both other groups ( P= 0.07 for both comparisons). These differences were not explained by differences in the blood pressures that were achieved. The serum creatinine concentration increased 24 percen t more slowly in the irbesartan group than in the placebo group ( P= 0.008) and 21 percent more slowly than in the amlodipine group (P=0.02). There we re no significant differences in the rates of death from any cause or in th e cardiovascular composite end point. Conclusions The angiotensin-II receptor blocker irbesartan is effective in protecting against the of nephropathy due to type 2 diabetes. This protecti on is independent of the reduction in blood pressure it causes. (N Engl J M ed 2001; 345: 851-60.) Copyright (C) 2001 Massachusetts Medical Society.