Mechanisms of nephrotoxicity.

The mammalian kidney is a dynamic and complex organ. Excretion of wastes is a primary function, but the kidney also plays a significant role in the regulation of total body homeostasis. Regulation of extracellular volume and control of electrolyte and acid-base balance are important renal functions. The kidney is a major site for formation of hormones that influence systemic metabolic functions, including erythropoietin, 1, 25 dihydroxy-vitamin D3, and renin. Recent evidence indicates that the kidney produces several vasoactive prostaglandins and kinins. A toxicological insult to the kidney could affect any or all of these functions. Few data are available that define specific cellular or subcellular sites of action of nephrotoxicants. Only rarely have receptors for individual agents been identified. Rather, in many cases it appears that several tissue constituents are influenced by a poison. There are two interrelated reasons for this apparent lack of specificity : (1) in contrast to a pharmacological effect which requires interaction with a distinct endogenous receptor, cell damage due to some chemicals may follow interruption of one or several required cellular functions ; (2) certain kidney cells may be more susceptible to damage merely because they are exposed to greater concentrations of chemicals than are other cells of the body as the result of this organ's unique anatomical and functional features.