Renal function tests as indicators of kidney injury in subacute toxicity studies

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Abstract

Several tests of renal function were conducted on adult, male Fischer 344 rats treated for 15 days with biphenyl, carbon tetrachloride or mercuric chloride. Each of the test compounds was administered at four different doses, the lowest of which was subnephrotoxic while the highest was sublethal. Tests included measurements of urine specific gravity, pH and volume, urinary excretions of glucose, protein, electrolytes, and several enzymes, serum concentrations of urea nitrogen, creatinine, and electrolytes, creatinine clearance, and kidney weight. Ability to concentrate urine after water deprivation, kidney morphology, and accumulation of organic ions by renal cortical tissue in vitro were also examined. In general, in vitro accumulation of organic ions, urinary concentrating ability, and kidney weight were the most sensitive and consistent indicators of nephrotoxicity. Standard urinalyses, serum analyses, quantitative enzymuria, and pathological changes in renal morphology were less sensitive and less consistent indicators of injury. The most advantageous tests, therefore, appeared to be those that measured total, functional renal capacity.

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