Urinary fibronectin excretion in streptozotocin-diabetic rats

Previous investigations performed in human diabetics demonstrate an increase in their urinary fibronectin excretion which was already present in subjects without microalbuminuria and which was elevated prior to functional restrictions. The present study was performed to examine whether in an experimental model these data obtained in men can be confirmed using an animal experimental model, and to further study pathomechanisms of diabetic nephropathy in rats. Fibronectin levels in serum and urine, and renal functional properties such as creatinine clearance, urinary albumin and protein excretion were studied in rats rendered diabetic with streptozotocin and compared with values of control and insulin treated animals for 5 months. Diabetic animals demonstrated the same creatinine clearance, but slightly decreased albumin and total protein excretion rates compared to controls and insulin "treated", euglycaemic animals. Diabetic rats showed a significantly increased excretion following day 42 compared to controls and insulin "treated" group. Concerning serum fibronectin, there was no significant difference between control, diabetic and insulin "treated" animals. The urinary fragment pattern of fibronectin was analyzed qualitatively by immunoblotting pattern and consisted of two main bands (M(r) 66,000 and 45,000). These bands were not altered in controls, insulin "treated" and diabetic rats, independent of the stage of renal involvement in diabetes. Present data provide evidence that fibronectin excretion is elevated in diabetic animals prior to functional restrictions, confirming results obtained in human diabetics. Therefore, determination of urinary fibronectin can serve as a more sensitive indicator for renal involvement in diabetes mellitus than microalbuminuria or changes in glomerular filtration rate. Urinary excretion may therefore serve as an early marker for the renal involvement in diabetes before the onset of clinical symptoms.