Expansion of Cortical Interstitium Is Limited by Converting Enzyme Inhibition in Type 2 Diabetic Patients with Glomerulosclerosis

Abstract

Abstract. Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, placebo-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 nondiabetic 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 (+1562 mg/d) but declined in PE patients (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light microscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (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 that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril prevents 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.

The Kidney in Diabetes: Dynamic Pathways of Injury and Repair

“…Another study compared renal structure before and after 38 months of treatment with enalapril or metoprolol in 13 type 1 diabetic patients with microalbuminuria [62], reporting no change over time in either group. In 19 type 2 diabetic patients, 2 years of treatment with perindopril prevented the progression of interstitial fibrosis compared with controls [63], without affecting glomerular structure. Thus, RAS blockade, effective in postponing ESRD, has not so far been shown to have a favourable effect on renal structure.…”

“…Thus, as clearly demonstrated by the studies performed to date [61][62][63], clinical trials using renal structure as an endpoint, especially in the early stages of DN, require large numbers and, most importantly, a long follow-up duration (likely 7-10 years). This would require the cooperation of industries and national funding agencies, along with strong commitment from the investigators and patients.…”