Susceptibility of the Renal System

Several factors are involved in the sensitivity of the kidney to a number of toxicants (Table 15.1), although the high renal blood flow and the increased concentration of excretory products following reabsorption of water from the tubular fluid are clearly of major importance. Although the kidneys comprise less than 1% of the body mass, they receive around 25% of the cardiac output. Thus significant amounts of exogenous chemicals and/or their metabolites are delivered to the kidney. 

A second important factor affecting the kidneys sensitivity to chemicals is its ability to concentrate the tubular fluid and, as a consequence, as water and salts are removed, to concentrate any chemicals it contains. Thus a nontoxic concentration in the plasma may be converted to one that is toxic in the tubular fluid. The transport characteristics of the renal tubules also contribute to the delivery of potentially toxic concentrations of chemicals to the cells. If a chemical is actively secreted from the blood into the tubular fluid, it will accumulate initially within the cells of the proximal tubule or, if it is reabsorbed from the tubular fluid, it will pass into the cells in relatively high concentration. 

Reabsorption and/or secretion of chemicals through tubular cells 

Activation of protoxicants to reactive, and potentially toxic, metabolites 

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