Characteristics of Proteinuria in Experimental Diabetes Mellitus

An impairment of protein charge selectivity has been invoked to explain 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 over 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 proteinuria in 24-h urine collections were evaluated at 3, 6, 9, and 12 months of diabetes. The Bradford method and mono- and bidimensional gel electrophoresis were used to determine and characterize proteinuria. Body 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 proteinuria 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 diabetic rats compared with the control group. When the charge and the size of 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 proteins were found to be immunoglobulin fragments. In the control group the pattern of proteinuria remained unchanged throughout. Thus, a charge permselectivity abnormality does exist in animal diabetes and its evaluation, together with that of size-selective proteinuria, contributes to the understanding and the monitoring of the diabetic kidney disease.