The Pathogenesis of Focal Glomerulosclerosis : Nonimmunologic Mechanisms of Glomerular Injury in Renal Ablation Model

The incidence of focal segmental sclerosis was studied in the two experimental models using two rat strains, Wistar and Nagase analbuminemia rats (NAR). In the Wistar rats, one week after left 2/3 kidney infarction, the right kidney was removed in Group 1 and the right ureter was ligated in Group 2. Glomerular hypertrophy and morphological changes such as epithelial reabsorption droplets and focal segmental sclerosis were observed in Group 1, but these changes were less severe in the rats of Group 2. In another experiment, the incidence of glomerular injury was studied in NAR which were characterized by analbuminemia and serve hyperlipidemia. Ten NAR underwent 5/6 nephrectomy, and were divided into two groups. Four rats were treated with captopril (500 mg/L in drinking water) and 6 rats were untreated. After 4 weeks, untreated NAR exhibited severe hypertension and moderate proteinuria, but captopril-treated NAR showed normotension and mild proteinuria. Morphological studies revealed that glomerular hypertrophy, massive reabsorption droplets in epithelial cells and segmental sclerosis developed in untreated NAR. Nevertheless, no pathological lesions were detected in captopril-treated animals, in spite of the fact that the degree of hyperlipidemia did not differ significantly between the two groups. These data suggest that focal segmental sclerosis was always preceded by glomerular hypertrophy, and hyperlipidemia did not play a crucial role in developing focal segmental sclerosis in renal ablation model