1. ¹Nephrology Division, Department of Internal Medicine, Genoa University, Genoa, Italy
2. ²Renal Immunopathology Centre, Associazione Nuova Nefrologia e Fondazione D'Amico per la Ricerca sulle Malattie Renali, San Carlo Hospital, Milan, Italy
3. ³Nephrology Division, Imperia Hospital, Imperia, Italy

Correspondence: G Garibotto, Nephrology Division, Department of Internal Medicine, Genoa University, Viale Benedetto XV, 6, Genoa 16132, Italy. E-mail: gari@unige.it

Received 31 January 2007; Revised 5 July 2007; Accepted 10 July 2007; Published online 12 September 2007.

Abstract

The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1_c and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein-cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients.