Molecular basis for several drug-induced nephropathies

A recent clinical advance has been the discovery that many drug-induced hepatic diseases result from the metabolic activation of chemically stable drugs to potent alkylating agents by the liver. In addition to the liver, however, the kidney also contains active enzyme systems capable of metabolically activating drugs and other chemicals. For this reason a systematic investigation of the possible role of metabolic activation in the pathogenesis of several drug-induced renal diseases has been undertaken. These laboratory results are reviewed in the light of the clinical spectrum of the renal injuries, and possible therapeutic implications of these new findings are briefly discussed. The potential use of these models of nephrotoxicity to probe a variety of physiologic and pathophysiologic mechanisms of renal function are noted.