Progressive glomerular sclerosis and renal failure in rat with 7/8 nephrectomy model

A model of progressive glomerular sclerosis and chronic renal failure was established in 7/8 nephrectomized rats. Three fourths of left kidney of six-week old Sprague Dawley rats were ligated and removed. One week later right kidney was removed. As controls 3/4 nephrectomized rats operated the same manner as 7/8 nephrectomized rats and sham operated rats were used. Remarkable excretion of the protein into the urine and rise in blood pressure were noted in all 7/8 nephrectomized rats. Eight weeks after 7/8 nephrectomy, serum creatinine rose as high as 2.8-0.3 mg/dl and BUN 260 + 65 mg/dl. In contrast, only minor degree of elevation of blood pressure, excretion of protein into the urine and elevation of serum creatinine were noted in 3/4 nephrectomized rats. Morphologically deposition of rat IgG, C3, fibrinogen and albumine were observed mainly on the capillary wall in 7/8 nephrectomized rats. Minor amount of deposition was observed in 3/4 nephrce-tomized rats. By light microscopy there were remarkable glomerular and tubular lesions in 7/8 nephrectomized rats. Most of the glomeruli showed hypertrophy, 40% of the glomeruli had cellular or fibrocellular crescent, 34% of glomeruli failed into global sclerosis or hyalinosis, tubular atrophy or enlargement and hyaline cast in the lumen and interstitial fibrosis were also noted. By electron microscopy detachment of epithelial and endothelial cells from the GBM, increase in the mesangial matrix, obliteration of the capillary lumen by fibrin, hyaline material were observed. Only minor degree of increase in mesangial matrix and epithelial degenerative lesions were observed and 3% of glomeruli were sclerosed in 3/4 nephrectomized rats. From these results 7/8 nephrectomized rats can serve as useful model for studying the mechanism of glomerular sclerosis or hyalinosis and effect of various drugs on glomerulonephritis.