Lewis EJ. Department of Nephrology， Rush-Presbyterian-St. Luke’s Medical Center， Chicago， Illinois 60612， USA. Diabetes mellitus is the most common cause of end-stage renal disease in the United States， accounting for about 50% of all new cases. Although we previously established the renoprotective benefits of angiotensin converting enzyme (ACE) inhibitors in patients with coexisting hypertension and type 1 diabetes， evidence of the renoprotective effect of ACE inhibitors in patients with type 2 diabetes is less clear.We conducted the Irbesartan Diabetic Nephropathy Trial (IDNT) to determine whether the angiotensin II receptor blocker (ARB) irbesartan slows the progression of nephropathy in patients with type 2 diabetes independently of its blood pressure (BP)-lowering effect. In this randomized， controlled trial， we found that irbesartan was associated with a 20% reduction in the risk for the primary composite end point (doubling of the baseline serum creatinine concentration， development of end-stage renal disease， or death from any cause) compared with placebo (P =.02) and a 23% reduction compared with amlodipine therapy (P =.006). These results were not explained by differences in the BP that was achieved.In a separate study， losartan was shown to reduce the risk for progression of renal disease in patients with type 2 diabetic nephropathy. Angiotensin II receptor blocker therapy has also been demonstrated to slow the progression to overt nephropathy when initiated early in the course of type 2 diabetic renal disease (ie， in patients with microalbuminuria). Based on these studies， ARBs are clearly effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of their BP-lowering effect. Preclinical studies with the newest ARB， olmesartan medoxomil， suggest that this agent may provide renoprotective benefits as well.