[Effect of oral adsorbent AST-120 in rats with chronic renal failure--mechanism of progression of renal failure by dietary protein].

ABSTRACT

Progression of renal insufficiency was evaluated in partially nephrectomized Sprague-Dawley rats at the age of 10 weeks, fed on the low (6%), usual (20%), and high (36%) protein diet (group 6C, 20C, and 36C). Effects of oral adsorbent AST-120 on these experimental uremic models were also examined (group 6A, 20A, 36A). All the rats underwent paired feeding, and survived during the experimental period of 3 weeks. GFR (inulin clearance) and RPF (para-amino hippurate clearance), as well as Ccr was measured before the sacrifice. Initial serum creatinine and Ccr were 1.7 mg/dl and 0.27 ml/min. The rats of group 36C showed progressive elevation of serum creatinine level and decrease in Ccr. At the end of the study, GFR was significantly lower in group 36C than in group 6C and 20C (0.19, 0.68, 0.87 ml/min respectively). Significant elevation of filtration fraction in group 36C suggested that the decrease in GFR mainly resulted from low RPF. Even in group 36C, no glomerular sclerosis was histologically demonstrated in the remnant kidney, and the mean planar area of the remnant glomeruli was significantly small, which might reflect low RPF. Tubulo-interstitial changes like dilatation of the urinary space and tubular epithelial flattening were prominent in group 36C. Beneficial effect of AST-120 was obvious in high protein diet groups. GFR and RPF were rather well preserved in group 36A (0.36 and 0.78 ml/min) with normal filtration fraction. Tubulo-interstitial damage was evidently mild in group 36A. These data suggested the presence of some humoral factors, which can be adsorbed by AST-120 in gastrointestinal tract, and responsible for the deterioration of renal function and tubulo-interstitial damage induced by high protein diet in the uremic condition. Besides hyperfiltration and glomerular hypertrophy, such humoral factors as suggested in this study may contribute to the progression of chronic renal failure to some extent.