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Pathology of the Urinary System

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Toxicologic Pathology for Non-Pathologists

Abstract

The kidney is one of the most common organs for drug- or chemical-induced toxicities to occur, and nephrotoxicosis remains an important clinical concern in human patients. Laboratory animals utilized in clinical studies successfully predict human renal toxicosis and may develop similar renal pathology at appropriate doses. Histopathologic lesions in the kidney associated with nephrotoxic injury tend to fall into two major types: those affecting tubules (often by small molecules or chemical agents) and those affecting glomeruli (more often by biologic therapies). There are stereotypic morphologies in the kidney which can occur from a variety of toxic insults, and they often resemble one another. By understanding the nature of a lesion based on the nomenclature and the location provided by the pathologist, it is possible to glean some information regarding the severity, potential reversibility, and even mechanism of a particular renal toxin. Just as importantly, familiarity with common spontaneous background lesions in rodents and other laboratory animals used in toxicologic studies provides a basis to discount the clinical relevance of such lesions. Successful interpretation and translation of nonclinical kidney toxicity data depends on understanding dose and exposure relationships, renal clearance and absorption, and species selectivity related to a given test article, as well as comorbidities, and potential drug interactions associated with the patient or susceptible population. New experimental modalities and novel biomarkers are being utilized to augment traditional kidney-related endpoints in toxicity studies and explore potential pathophysiologic mechanisms of nephrotoxins to better inform the clinical safety of test articles and help drive decision-making.

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  1. Pathology, GlaxoSmithKline, Collegeville, PA, USA

    Kendall S. Frazier

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  1. North Carolina Laboratory, Experimental Pathology Laboratories, Inc., Durham, NC, USA

    Thomas J. Steinbach

  2. Charles River Laboratories, Inc., Mattawan, MI, USA

    Daniel J. Patrick

  3. MEC Regulatory and Toxicology Consulting, LLC, Moorpark, CA, USA

    Mary Ellen Cosenza

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Frazier, K.S. (2019). Pathology of the Urinary System. In: Steinbach, T., Patrick, D., Cosenza, M. (eds) Toxicologic Pathology for Non-Pathologists. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9777-0_6

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