ABSTRACT
The kidney is the predominant organ involved in regulation of extracellular volume and in control of electrolyte and acid base balance. The kidney is often the main site for excretion of many drugs and drug metabolites and is therefore exposed to a variety of potential toxicants. The renal medulla offers unique problems concerning nephrotoxicity. Because of the low blood flow to the medulla, relatively less potential toxicant might enter this region via the bloodstream than in the cortex. The formation of urine begins at the glomerulus where an ultrafiltrate of plasma is formed. In addition, active secretion of toxicants occurs in the proximal tubule which can result in high intracellular concentrations of a chemical. The proximal tubule is therefore uniquely susceptible to aminoglycoside toxicity due to filtration and the presence of anionic binding sites along the luminal membrane. Any or all of these functions could become targets for toxicants.
