A study on establishment of a renal toxicity model using nephretomized rats

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To establish a renal toxicity model using 5/6 nephretomized rats, changes of biochemical parameters and histological findings were sequentially investigated in 5/6 nephrectomized rats. Changes of creatinine clearance and electrolyte reabsorption, indicatorsforglomerular and tubaular functions, respectively, were divided into three stages : a reduction at weeks 2 to 4after nephrectomy, a slight increase from weeks 6 to 10, and a reduction again thereafter. These changes were considered to be correlated to alteration of renal function after nephrectomy : the early stage indicating acute renal failure caused by marked decrease of nephron units, the middle one showing physiological compensatory adaptation, and the late one being attributed to an onset of chromic renal failure, respectively. These results indicate that clinical biochemical parameters such as creatinine clearance and electolyte reabsorption are good indicators fo distinguish three stages of renal dysfunction in 5/6 nephrectomized rats. In addition, morphological canges were also divided similarly into same stages.To examine the effect of renal toxicants in nephrectomized rats, gentamycin and puromycin were tested. Gentamycin-induced tubular lesions worsened biochemically and morphologically in the nephrectomized rats treated when gentamycin was given at the early, middle or late stages, especially in the middle stage compared with those in the sham operated rats. In contrast, the increase in glomerular toxicity was only detectable in nephrectomized rats by biochemical indicators when low-dose puromycin wasgiven at the middle stage. The result suggests that some biochemical parameters may be morae sensitivethan morphological examinaation to detect glomerular toxicity.In conclusion, our study described above suggests that the 5/6 nephrecomized rat is a useful model for detection of renal toxicity and that the middle stage is a more effective time to detect it.