Nephrotoxicity induced by non-steroidal anti-inflammatory drugs was investigated using the laboratory rat. Standard biochemical investigations, together with urinary enzyme examination, complemented the results of organ weight analysis and conventional pathological examinations. Variations in kidney function caused by strain of rat, age, sex and spontaneous pathological change were encountered. These factors are important when assessing the degree of nephrotoxicity induced by large doses of analgesics. The simple assessments performed on urine and blood samples and on the kidneys were adequate to detect necrotic change, but less severe changes were difficult to evaluate. With aspirin it was difficult to induce kidney damage consistently, although susceptibility could be modified. Similarly, with phenylbutazone the kidney was not consistently found to be a common target organ. The nephrotoxic potential of indomethacin was difficult to define because of the ulcerogenic effects of this drug on the intestinal tract. Analgesic nephropathy is more likely to be defined by epidemiological studies. Rodent data are of doubtful relevance in predicting nephrotoxicity in man.
|Date of Award||1981|