Early manifestations of nephropathy in alloxan-treated rats

Abstract

An early stage of diabetic nephropathy was studied. Rat renal function was evaluated by clearance techniques, 7 or 15 days after alloxan administration (groups A7 and A15). Significant diminutions of glomerular filtration rate (inulin clearance) and p-aminohippurate clearance were observed in alloxan-treated rats. Diabetic animals presented glucosuria and enhanced water excretion. A natriuretic response was only observed in A15-rats. Arterial pressure increased along time, and enlarged lipid deposits in glomeruli and vessels of A7-kidney sections were observed. Thus, a vascular compromise at this time was suggested. To better characterize the set up of the renal dysfunction, other studies were performed in A7-group. Urinary protein excretion remained unchanged while a higher level of glycosylation of urinary proteins was observed in A7-rats. Histological studies revealed a normal general morphology in kidneys from diabetic rats. Immunohistochemical analysis in renal sections showed enlarged deposits of fibronectin in glomeruli and interstitium of alloxan-treated rats. Higher myeloperoxidase activity was observed in renal cortex from diabetic animals indicating leukocytes infiltration. These results indicated that 7 days after hyperglycemia induction, the animals presented a renal dysfunction characterized by hemodynamic alterations associated with vascular and glomerular structural impairments, without modifications in tubular function. The higher level of protein glycosylation and the inflammatory process at this early stage could be responsible for the beginning of diabetic nephropathy.