Evaluating the nephrotoxicity of cytotoxic agents using a rat kidney perfusing model

Abstract

The nephrotoxicity of a number of chemother apeutic drugs may be a great problem from the clinical point of view, especially under a high dose therapy. It has been shown that, under certain circumstances, the maximum dose of a cytotoxic agent is not administered by the tox icity in the bone marrow but by the renal toxic ity. The renal mechanisms of action of cytotoxic drugs are poorly understood. The kidney seems to be very sensitive to the actions of these substances. In addition, the kidney plays a spe cial role in comparison with other organs be cause of the existence of an osmotic gradient in the renal medulla that results in a higher local concentration of systemically given cytotoxic drugs than in the remaining organism. The exper imental model of the isolated perfused rat kidney is a powerful tool to investigate the nephrotoxicity of chemotherapeutic agents. In this preparation, functional parameters can be changed in a con trolled manner, and systemic influences on renal function are eliminated.