Genetic factors in the development of nephropathy in diabetic Lewis and DA rats

1. Streptozotocin was used to induce diabetes in two inbred strains of rats, Lewis and DA, known to have different glomerular properties. 2. Dietary protein intake, weight and plasma glucose were monitored during the course of the experiment, and, at regular intervals, urine collections were made utilizing metabolic cages. 3. No significant differences were found in protein intake or plasma glucose between the two strains. 4. Proteinuria was higher in the diabetic Lewis rats than in the diabetic DA rats, and the difference became progressively greater with the passage of time. After 6 months of diabetes, the median values for proteinuria were 19.9 mg/24 h in the Lewis rats and 9.0 mg/24 h in the DA rats. 5. Electron microscopic examination revealed a greater degree of mesangial expansion in the glomeruli of the Lewis rats than in those of the DA rats after 6 months of diabetes. The median fractional mesangial area was 44.8% in the diabetic Lewis rats and 31.4% in the diabetic DA rats. 6. These results suggest that Lewis rats possess an inherited susceptibility to diabetic nephropathy, and that DA rats are relatively resistant. These differences in susceptibilities support the hypothesis that inherited glomerular properties determine an individual's susceptibility to diabetic nephropathy.