Chapter 11 – Urinary System
2018
The urinary system is a common target site for toxicity of drugs and environmental chemicals. The kidney is particularly susceptible because of the high blood flow to this organ relative to its mass and the unique property of renal tubular epithelium in concentrating urine and its constituents including drugs and chemicals. Three main clinical entities in humans associated with drug effects on kidney are the nephrotic syndrome, acute renal failure (ARF), and chronic renal failure. It is estimated that about 20% of all ARF cases in humans are related to pharmaceutical agents and that 2% to 5% of patients admitted to the hospital will develop drug-induced acute renal insufficiency. An estimated 500,000 new patients exposed to drugs on a worldwide basis each year develop end-stage renal disease. The estimated annual costs of dialysis and transplants are substantial, representing a major challenge to the pharmaceutical and chemical industries for developing safer molecules.
The gold standard method for identification of toxicity to the urinary system is light microscopic examination, supplemented with renal function tests and biochemical markers of cell injury in blood and urine. To refine the risk assessment, establishment of the cellular and subcellular organelle targets of xenobiotic injury by the pathologist forms a cornerstone in expanding the mechanistic understanding of the injury process. Through identification of cellular and subcellular targets, the most sensitive biomarkers can be identified to noninvasively monitor for the presence of a specific xenobiotic insult in laboratory animals and eventually in humans. This chapter emphasizes the structural and biochemical changes and the potential mechanisms involved in urinary tract toxicity.
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