Study on the initiation time of drug treatment for chronic renal failure

Abstract

In order to examine the initiation time of drug treatment for chronic renal failure by the removal of certain substances which are accumulated in the digestive tract, experiments were carried out on 60 male Sprague-Dawley rats weighing 285-325g. The rats were first subjected to 2/3, 3/4 and 4/5 nephrectomy (n = 20). The experiments were begun at 2 weeks after the surgery, and were performed over an 8-week period. Half of each group of nephrectomized rats (n = 10) was administered the oral adsorbent, 1 g/day of Kremezin (AST-120, Kureha Chemical Industry Co, Tokyo), and pair feeding was done in each group of nephrectomized rats. The administration of Kremezin delayed the occurrence of glomerular hypertrophy, glomerulosclerosis, hypertrophy of the glomerular epithelial cells, flattening of the tubular cells, dilation of the tubular cavity and infiltration of monocytes into the interstitium in the 2/3 nephrectomized rats. In addition, the administration of Kremezin delayed the appearance of proteinaceous cast formation in the tubules, ballooning of the tubular cells, an increase in systemic blood pressure and an increase in urinary protein excretion in the 3/4 and 4/5 nephrectomized rats. These findings indicated that the correction of an abnormal milieu within the digestive tract in chronic renal failure can delay its progression. Since the level of the creatinine clearance in the 2/3 nephrectomized rats was equal to approximately 60% of the creatinine clearance in normal rats, it is suggested that drug treatment for chronic renal failure with Kremezin should be initiated before the level of the creatinine clearance decreases to 60% of creatinine clearance in normal human.