Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group.
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.
Cordonnier
D J
DJ
Service de Néphrologie et d'Endocrinologie de Centre Hospitalier Universitaire de Grenoble, France. Daniel.Cordonnier@ujf-grenoble.fr
Pinel
N
N
Barro
C
C
Maynard
M
M
Zaoui
P
P
Halimi
S
S
Hurault de Ligny
B
B
Reznic
Y
Y
Simon
D
D
Bilous
R W
RW
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001707:Biopsy, Needle; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000008:administration & dosage*; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D020913:Perindopril; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril