CHARACTERISTICS OF PROTEINURIA IN EXPERIMENTAL DIABETES-MELLITUS

An impairment of protein charge selectivity has been invoked to explai n the initial anionic proteinuria in diabetic nephropathy. The aims of this work were to investigate charge and size protein permselectivity abnormalities in experimental diabetes and to monitor these changes o ver time after diabetes induction. Diabetes was induced in 56 Sprague- Dawley male rats by streptozotocin; the control group was represented by 38 normal rats. Blood glucose, body weight, urine volumes, and prot einuria in 24-h urine collections were evaluated at 3, 6, 9, and 12 mo nths of diabetes. The Bradford method and mono- and bidimensional gel electrophoresis were used to determine and characterize proteinuria. B ody weight increase was lower (P < 0.05, P < 0.0001, P < 0.05 at 3, 6, and 12 months, respectively), urine volumes were greater (P < 0.001, P < 0.05, P < 0.05 at 6, 9, and 12 months, respectively) and the prote inuria was significantly increased (P < 0.05 at 3 months, P < 0.001 at 6 months, P < 0.01 at 9 months, and P < 0.05 at 12 months) in diabeti c rats compared with the control group. When the charge and the size o f urine proteins were considered, small (30 kDa) and anionic proteins were found to be mainly excreted in diabetic rats, at 3 months of the disease; at 6 months, higher amounts of albumin and cationic proteins with higher molecular weight (50 kDa) were also found in the urine; at 9 and 12 months the changes previously described were associated with an excretion of proteins weighing about 75 kDa. The 30- and 50-kDa pr oteins were found to be immunoglobulin fragments. In the control group the pattern of proteinuria remained unchanged throughout. Thus, a cha rge permselectivity abnormality does exist in animal diabetes and its evaluation, together with that of size-selective proteinuria, contribu tes to the understanding and the monitoring of the diabetic kidney dis ease. (C) 1994 Academic Press, Inc.