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Services de Néphrologie et
d'Endocrinologie des Centres Hospitaliers Universitaires de Grenoble, Centre
Hospitalier Universitaire de Grenoble, France
Services de Néphrologie et
d'Endocrinologie des Centres Hospitaliers Universitaires de Caen, Centre
Hospitalier Universitaire de Grenoble, France
Services de Néphrologie et
d'Endocrinologie des Centres Hospitaliers Universitaires de Creteil, Centre
Hospitalier Universitaire de Grenoble, France
§
Laboratoire de Pathologie Cellulaire, Centre Hospitalier Universitaire de
Grenoble, France
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GREPI (Groupe de Recherche et d'Etudes des Processus Inflammatoires),
Centre Hospitalier Universitaire de Grenoble, France
#
University of Newcastle upon Tyne, United Kingdom
Correspondence to Daniel Cordonnier, Service de Néphrologie, Centre Hospitalier Universitaire, BP 217X, 38043 Grenoble, Cedex 09, France. Phone: 33 04 76 76 55 23; Fax: 33 04 76 76 52 63; E-mail: Daniel.Cordonnier{at}ujfgrenoble.fr
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.
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