Sensitivity of urinary enzymes as indicators of renal toxicity of the anticancer drug cis-platin.
Rats were intravenously injected with cis-platin in order to evaluate the sensitivity of noninvasive means of detecting renal toxicity. Doses of 8 mg/kg and 2 mg/kg were used and 7 urinary parameters (osmolality, glucose, protein, and 4 enzymes) were compared with blood urea nitrogen (BUN) and histology. Urinary enzymes usually were elevated by Day 2 posttreatment and in two cases by Day 1. Protein and glucose were elevated by Day 3 and demonstrated a greater quantitative change (10-12X control) than did urinary enzymes (2-3X controls). Enzymes, protein, and glucose all returned to control levels by Day 7 or 8, and most parameters were re-elevated again by Day 10 or 12. BUN was unaltered at the lowest dose and was increased to three times control by Day 3 after the highest dose. Cis-platin induced a mild nephrosis at the lowest dose and a proximal tubular necrosis at the highest dose. The lesion occurred at the corticomedullary junction. Biochemical changes did not correspond to the times of greatest morphological changes. Large day-day and animal-animal variation made selection of a most sensitive parameter difficult. It is concluded that one parameter is insufficient to define early renal toxicity and that a battery of several parameters would provide a better evaluation of the onset of renal toxicity.
D000118:Acetylglucosaminidase / Q000652:urine; D000626:Aminopeptidases / Q000652:urine; D000818:Animals; D001806:Blood Urea Nitrogen; D018826:CD13 Antigens; D002945:Cisplatin / Q000633:toxicity*; D006029:Glycosuria; D007674:Kidney Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009994:Osmolar Concentration; D011507:Proteinuria; D051381:Rats; D011916:Rats, Inbred F344; D014556:Urine; D000520:alpha-Glucosidases / Q000652:urine; D005723:gamma-Glutamyltransferase / Q000652:urine
D005723:gamma-Glutamyltransferase; D000520:alpha-Glucosidases; D000118:Acetylglucosaminidase; D000626:Aminopeptidases; D018826:CD13 Antigens; D002945:Cisplatin