EARLY MANIFESTATIONS OF NEPHROPATHY IN ALLOXAN-TREATED RATS

An early stage of diabetic nephropathy was studied. Rat renal function was evaluated by clearance techniques, 7 or 15 days after alloxan adm inistration (groups A7 and A15). Significant diminutions of glomerular filtration rate (inulin clearance) and p-aminohippurate clearance wer e observed in alloxan-treated rats. Diabetic animals presented glucosu ria and enhanced water excretion. A natriuretic response was only obse rved in A15-rats. Arterial pressure increased along time, and enlarged lipid deposits in glomeruli and vessels of A7-kidney sections were ob served Thus, a vascular compromise at this time was suggested. To bett er characterize the set up of the renal dysfunction, other studies wer e performed in A 7-group. Urinary protein excretion remained unchanged while a higher level of glycosylation of urinary proteins was observe d in A 7-rats. Histological studies revealed a normal general morpholo gy in kidneys from diabetic rats. Immunohistochemical analysis in rena l sections showed enlarged deposits of fibronectin in glomeruli and in terstitium of alloxan-treated rats. Higher myeloperoxidase activity wa s observed in renal cortex from diabetic animals indicating leukocytes infiltration. ' These results indicated that 7 days after hyperglycem ia induction, the animals presented a renal dysfunction characterized by hemodynamic alterations associated with vascular and glomerular str uctural impairments, without modifications in tubular function. The hi gher level of protein glycosylation and the inflammatory process at th is early stage could be responsible for the beginning of diabetic neph ropathy.