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Functional-morphologic correlations in assessing renal toxicity.

G H Hottendorf

    Toxicologic Pathology
    |January 1, 1986
    PubMed
    Summary
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    Clinical function tests struggle to identify drug-induced kidney toxicity. Preclinical morphologic assessments and biochemical data effectively rank nephrotoxicity, suggesting animal models are superior for evaluating drug safety.

    Area of Science:

    • Toxicologic pathology
    • Nephrology
    • Pharmacology

    Background:

    • Assessing drug-induced renal toxicity is crucial for toxicologic pathologists.
    • Clinical assessments rely on renal function tests, while preclinical studies use functional and morphologic evaluations.
    • Existing renal function tests may lack sensitivity in detecting nephrotoxicity.

    Purpose of the Study:

    • To evaluate the relative sensitivity of functional and morphologic indicators of nephrotoxicity.
    • To compare the ability of different data bases to rank the nephrotoxicity of aminoglycosides.

    Main Methods:

    • Examined three data bases: clinical function tests, preclinical renal morphology, and biochemical/mechanistic comparisons.
    • Analyzed data for the three most widely used aminoglycosides.

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  • Compared the discriminatory power of each data base in ranking nephrotoxicity.

    • Main Results:

    • Clinical function tests could not differentiate the nephrotoxic liability among the three aminoglycosides.
    • Preclinical renal morphology and biochemical/mechanistic data bases clearly distinguished the drugs.
    • Both preclinical data bases ranked the aminoglycosides in the same order of nephrotoxicity.

    Conclusions:

    • Clinical renal function tests may be inconclusive for comparing drug nephrotoxicity due to insensitivity.
    • Preclinical assessments using morphologic evaluation of renal tissue damage in animals may offer a more reliable comparison.
    • Morphologic assessments in preclinical studies are valuable for evaluating drug-induced kidney toxicity.