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 progression of several nephropathies. This study describes a multicenter, prospective, double-blind, pla- cebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance .60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of non- diabetic nephropathy. The remaining 22 were randomized (11 to Perindopril (PE), 11 to placebo (PO)), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (11562 mg/d) but declined in PE patients (2156 mg/d) (P , 0.05). Morphometric analysis was performed by light micros- copy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 6 5.3 versus 40.2 6 11.1%; P 5 0.001) but was unchanged in PE patients (33.8 6 4.9 versus 34.7 6 6.6%; P 5 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril pre- vents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.