ABSTRACT
The kidney is a common toxicologic target organ for pharmaceutical therapeutic agents, and lesions of the urinary tract are frequently encountered in preclinical toxicologic studies by pathologists. Renal injury may occur as a result of direct effects on tubules or glomeruli or indirectly via altered hemodynamics. High renal blood ow (RBF) (as much as 25% of cardiac output) and/or proportionally high renal excretion associated with many drugs, coupled with the high doses of test articles typically given in preclinical toxicity studies, often result in effectively high local compound concentrations in the kidney of animals in these studies. The inherent high metabolic activity and high oxygen consumption of renal epithelium, coupled with the ability of the kidney to concentrate drugs in the urine, all predispose this organ to toxic injury. In addition, the signicant transporter activity of the renal epithelium makes the kidney further susceptible to injury through cell specic uptake of metabolites from both urinary and blood interfaces as well as from drug-drug interactions when agents are administered in combination therapies. The specic pattern of renal injury is dependent on the nature of the drug, its toxicokinetic properties, clearance prole and particular metabolic attributes, and, ultimately, the local tissue concentration of the agent and length of time of exposure.
