title: Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group.
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.
authors.affiliation: Service de Néphrologie et d'Endocrinologie de Centre Hospitalier Universitaire de Grenoble, France. Daniel.Cordonnier@ujf-grenoble.fr
authors.forename: D J
authors.initials: DJ
authors.lastname: Cordonnier
authors.forename: N
authors.initials: N
authors.lastname: Pinel
authors.forename: C
authors.initials: C
authors.lastname: Barro
authors.forename: M
authors.initials: M
authors.lastname: Maynard
authors.forename: P
authors.initials: P
authors.lastname: Zaoui
authors.forename: S
authors.initials: S
authors.lastname: Halimi
authors.forename: B
authors.initials: B
authors.lastname: Hurault de Ligny
authors.forename: Y
authors.initials: Y
authors.lastname: Reznic
authors.forename: D
authors.initials: D
authors.lastname: Simon
authors.forename: R W
authors.initials: RW
authors.lastname: Bilous
mesh_terms: 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
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril