Differential effects of nephrotoxic agents on renal transport and metabolism by use of in vitro techniques.

A number of studies by the author and other investigators are reviewed in which the in vitro kidney slice technique has been used to evaluate the nephrotoxicity of various compounds. The kidney slice technique can be used to determine the effect of prior drug treatment of laboratory animals on renal organic acid (p-aminohippurate) or organic base (N-methylnicotinamide) transport, on glucose synthesis, and on oxygen consumption by renal coritical slices. The nephrotoxic agents uranyl nitrate and potassium dichromate exert inhibitory effects on renal function, althouhg both agents enhance organic base transport at low doses and potassium dichromate enhances organic acid transport at moderate doses. Enhanced PAH transport has been found to be a sensitive indicator of gentamicin induced nephrotoxicity, while inhibition of other parameters has been reported. The tissue slice method is less effective in evaluation chronic nephrotoxicity such as that produced by lead. The inhibitory effect of mercurial diuretics has been shown to be due to the general depression of metabolic activity by mercury. The kidney slice technique has been found to be a sensitive indicator in the assessment of halogenated hydrocarbon-induced nephrotoxicity. Differential effects of compounds on in vitro organic acid and base trasport provides information about the transport of these compounds as well as about their nephrotoxicity. Although it is often desirable to perform in vivo tests or other in vitro renal function tests, the kidney slice technique has proved to be extremely useful in toxicological evaluations.