Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis

Renal interstitial expansion is now considered a useful marker of progressi on of several nephropathies. This study describes a multicenter, prospectiv e, double-blind, placebo-controlled, randomized trial of the effects of Per indopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 d iabetic patients with proteinuria ranging from 70 to 4210 mg/d and relative ly preserved GFR (creatinine clearance >60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the pr esence of nondiabetic nephropathy. The remaining 22 were randomized (11 to Perindopril [PE], 11 to placebo [PO]), and 19 (9 PE, 10 PO) underwent follo w-up biopsy at 2 yr, BP was controlled equally in both groups throughout. P roteinuria increased in PO patients (+1562 mg/d) but declined in PE patient s (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light micr oscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial f ractional volume identical at baseline increased significantly in PO patien ts (31.7 +/- 5.3 versus 40.2 +/- 11.1%; P = 0.001) but was unchanged in PE patients (33.8 +/- 4.9 versus 34.7 +/- 6.6%; P = 0.50). It is concluded tha t: (1) nondiabetic nephropathy is present in approximately 15% of albuminur ic type 2 diabetic patients; and (2) Perindopril prevents interstitial expa nsion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of inters titial changes in type 2 diabetic patients with nephropathy.