Takahashi S, Okada K
Nishi-Kofu National Hospital, Yamanashi, Japan.
Nihon Jinzo Gakkai Shi. 1993 Jun;35(6):765-76.
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.
为了通过清除在消化道中蓄积的某些物质来研究慢性肾衰竭药物治疗的起始时间,对60只体重285 - 325g的雄性Sprague-Dawley大鼠进行了实验。首先对大鼠进行2/3、3/4和4/5肾切除术(n = 20)。实验在手术后2周开始,持续8周。每组肾切除大鼠的一半(n = 10)给予口服吸附剂,每天1g的可利美特(AST-120,日本久光化学工业株式会社,东京),并对每组肾切除大鼠进行配对喂养。可利美特的给药延缓了2/3肾切除大鼠肾小球肥大、肾小球硬化、肾小球上皮细胞肥大、肾小管细胞扁平、肾小管腔扩张以及单核细胞浸润到间质的发生。此外,可利美特的给药延缓了3/4和4/5肾切除大鼠肾小管内蛋白质管型形成、肾小管细胞气球样变、全身血压升高以及尿蛋白排泄增加的出现。这些发现表明,纠正慢性肾衰竭消化道内的异常环境可以延缓其进展。由于2/3肾切除大鼠的肌酐清除率水平约等于正常大鼠肌酐清除率的60%,因此建议在肌酐清除率水平降至正常人肌酐清除率的60%之前,开始用可利美特对慢性肾衰竭进行药物治疗。