Chronic renal failure after nephrotoxic nephritis in rats: Contributions to progression

Chronic renal failure after nephrotoxic nephritis in rats: Contributions to progression. In rats dietary protein restriction decreases the rate of progressive glomerulosclerosis and the development of renal failure after subtotal nephrectomies. The present experiments were designed to see whether dietary protein had similar effects on renal failure after nephrotoxic nephritis (NTN). Groups of rats were fed isocaloric diets containing 8%, 18% and 78% casein. Irrespective of whether the diets were introduced 7 days or 30 days after induction of nephritis by a single injection of rabbit anti-rat nephrotoxic globulin, rats on 8% casein and 78% casein had significantly lower plasma creatinines than rats fed with 18% casein. Semiquantitative scoring systems were used to assess glomerular sclerosis, tubular atrophy and tubular calcification. Rats on 8% protein had significantly lower glomerular sclerosis scores than the other two groups. Tubular atrophy scores were similar in rats on 8% and 78% casein and significantly lower than those of rats on 18% casein. All rats on 8% and 18% casein diets had tubular calcification whereas rats on 78% casein did not. This suggested that the normal relation between glomerular sclerosis and tubular atrophy after NTN was altered by a 78% casein diet. This was confirmed by the slopes of the regression equation for glomerular sclerosis on tubular atrophy (0.54 ± 0.07) for rats on 78% casein compared to the slopes of the regression equations for the other two groups which were 1.12 ± 0.10 and 1.00 ± 0.12, respectively. This difference is highly significant statistically, P < 0.1 × 10-5; (one-way analysis of variance). These results show that dietary protein has a variable effect on the development of renal failure after nephrotoxic nephritis. They suggest the presence of separate glomerular and tubular contributions to progressive renal failure in this model