INTRODUCTION

The kidneys are particularly susceptible to xenobioticinduced toxic injury. This is due primarily to the unique structure and function of these highly dynamic organs. The nephron, the functional unit of the kidney, consists of the glomerulus and at least 12 morphologically and functionally distinct tubular segments.

Individual nephron segments contain one or more cell types which are structurally and functionally related; and these cell types may differ in their susceptibility to toxicant-induced injury. Factors which may predispose the kidneys to toxicant-induced injury include: 1) the high rate of renal blood flow (approximately 25% of total cardiac output); 2) mechanisms for concentrating toxicants within the tubular fluid; 3) transport systems capable of concentrating toxicants within cells; and 4) a substantial capacity for xenobiotic biotransformation. The renal cortex receives 85 to 90% of the total renal blood flow. As a result, the renal cortex, which is 90% proximal tubular tissue, may be preferentially exposed to blood-borne toxicants. Proximal tubular cells contain several active transport systems for the secretion and/or reabsorption of xenobiotics. Toxicants may achieve high concentrations within proximal tubular cells if they are substrates for one or more of these transport systems. In addition, protein endocytotic mechanisms located in the luminal membrane of proximal tubular cells also may contribute to reabsorption and intracellular concentration of toxicants. The renal cortex contains cytochrome P-450-dependent mixed-function oxidases which are capable of activating xenobiotics to toxic, reactive intermediates.