[Drug nephrotoxicity: mechanisms of action]

Drug-induced nephrotoxicity is very frequent. The kidney is particularly prone to the actions of nephrotoxins. Indeed, high levels of toxin can be delivered to the kidney secondary to the large blood supply in this organ. There is also an enormous surface area of the renal tubular epithelium providing sites for toxin interaction and uptake. There is specific transport mechanisms occurring in the kidney as concentrating mechanisms leading to a possible urinary and interstitial concentrations of agents. We have also to consider the presence of metabolic processes within renal tubular cells which release toxic components of drugs or produce toxic by products of metabolism. It is also to be noted that tubular cells have a high metabolite rate and this can be subject to perturbations induced by toxins. All parts of the kidney may be involved in toxic nephropathies: glomerular, tubular, interstitial or vascular lesions could occur. The mechanisms of these lesions may be toxic or immunologic. Tubular cells may be altered in multiple sites. Besides contributing to the structural framework for membranes, membrane phospholipids have been shown to play important roles in regulating membrane permeability properties. Toxins may alter membrane phospholipid metabolism as lysophospholipids and free fatty acids have toxic detergent properties. The deleterious interactions of calcium with mitochondria are particularly important for understanding the role of calcium in cell injury. Calcium may induce mitochondrial membrane permeability alterations, activation of membrane phospholipases, activation of specific ion channels, decrease or increase enzymatic actions, increase cellular contractile components, or induce modifications or cytoskeletal. Nephrotoxins could be accumulated in lysosomes and thus have the potential to alter lysosomal functions.(ABSTRACT TRUNCATED AT 250 WORDS)