Responses of the Kidney to Toxic Compounds

Abstract

Chemically induced injury to the kidney can occur as a result of the direct effect of a chemical or a metabolite on renal cells or indirectly by altering renal haemodynamics, or by a combination of both. The site along the nephron which is damaged is frequently the site of cellular accumulation of the chemical or a metabolite. Nephrotoxic chemicals may enter the renal tubular cells by endocytosis either as the chemical per se or a chemical‐protein complex. Alternatively some chemicals are actively transported into renal cells on endogenous transport systems. Once concentrated inside cells, the chemical may be released from its intracellular binding site and cause cytotoxicity. Alternatively, renal specific metabolism by enzymes such as cytochrome P450 or cysteine conjugate β‐lyase may lead to the generation of reactive electrophiles that can cause cytotoxicity. The precise subcellular biochemical mechanism leading to cytotoxicity for most chemicals has not been established, but mitochondria are frequently, but not exclusively, a critical target for toxicity.