ABSTRACT

The kidney is a target organ for a wide range of drugs and nontherapeutic chemicals. Although some drugs (e.g., gentamicin, amphotericin B) and nontherapeutic chemicals (e.g., carbon monoxide, cyanide ion) can induce nephrotoxicity through the actions of the parent compound, a large number of toxicants require bioactivation via metabolism to produce the ultimate nephrotoxicant species. In some cases, initial biotransformation can occur in extrarenal organs so that the penultimate or ultimate toxicant species is carried to the kidney via the blood. For example, hepatic biotransformation of haloalkanes or haloalkenes can result in the formation of glutathione, cysteine and N-acetylcysteine conjugates of the halocarbons (Dekant et al., 1993). These conjugates are then transported via the circulation to the kidney, where further biotransformation occurs and toxicity is observed in proximal tubular cells of the S3 segment (Dekant et al., 1993; also see Chapter 23 for an in-depth discussion of these nephrotoxicants). In other cases, the parent nephrotoxicants (e.g., chloroform) (Anders, 1989; Smith, 1986) are biotransformed completely in the kidney to their ultimate nephrotoxicant species.