Sensitivity of urinary enzymes as indicators of renal toxicity of the anticancer drug cis-platin

Abstract

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.