ABSTRACT
The cellular and anatomical complexity of the kidney is essential to its function. Alterations in renal cellular function may increase the risk of toxic damage to the kidney, and also to other organ systems. Notable age, sex, and species related differences in renal physiology and anatomy affect susceptibility to exogenous insults. Nephrotoxicity can be a common finding in laboratory animals and humans following exposure to xenobiotics. Laboratory animals, including rats, dogs, and monkeys, are often used in the risk assessment of new therapeutics and chemicals or to understand etiopathogenesis of potential renal toxicities in humans. In conventional nonclinical safety assessment studies, laboratory animals are exposed to xenobiotics during all stages of their lifespan, including fetal, perinatal, juvenile, and adult. Therefore, refinement of risk assessment requires not only specific knowledge of the molecular, biochemical, and structural effects of drugs and chemicals, but also of how an animal’s age, sex, species, breed, and strain contribute to the toxic effects of xenobiotics. This chapter emphasizes the role of age, gender, and species in renal physiology and nephrotoxicity, the mechanisms by which changes occur, and their relationship with risk assessment in the human.
