ABSTRACT
The susceptibility of the mammalian kidney to the adverse effects of toxicants can be attributed to anatomical, physiological, and biochemical aspects of renal function. The kidneys receive a disproportionately large blood flow to support glomerular filtration and to sustain renal metabolism; high blood flow results in greater exposure to bloodborne chemicals than occurs in less-well perfused organs. Solute and water reabsorption along the nephron enriches the tubular fluid in those chemicals that remain in the tubular lumen, exposing the cells of the nephron to higher concentrations of toxicants than occur in the general circulation; chemicals with low aqueous solubilities may precipitate or crystalize, causing obstruction of the nephron or obliteration of renal tissue. Chemicals that are substrates for organic solute transport systems gain entry and accumulate within proximal tubule cells in amounts that are not reflected in cells outside of the kidney, leading to nephrotoxicity. Intrarenal metabolism of nontoxic chemicals can produce toxic metabolites that subsequently damage renal structures and functions.
