Renal tubular transport and nephrotoxicity of DDA

Since DDA [bis(p-chlorophenyl)acetic acid] has been shown to be transported and concentrated by the renal proximal tubule, this metabolite of DDT has been postulated to be a potential nephrotoxic agent. The present study explored the renal transport of DDA in the isolated, perfused rat kidney and the effects of DDA on renal function. When DDA (0.6 microM) was present in a dextran perfusate which eliminated DDA-colloid binding, the DDA/inulin clearance ratio was congruent to 0.05; however, some metabolism of DDA was apparent. During these studies, DDA had no effect on the glomerular filtration rate and the fractional reabsorption of Na, K or H2O. To determine the concentration of DDA which would produce an effect on renal cellular function, studies were performed with renal cortical slices. DDA at media concentrations greater than or equal to 0.1 mM were needed to produce significant alterations in tetraethylammonium transport, tissue oxygen consumption and intracellular electrolyte composition; however, no effect was demonstrated on Na-K-ATPase activity although DDA did affect Mg-ATPase activity. In conclusion, DDA at a 0.6 microM perfusate concentration undergoes net tubular reabsorption and metabolism without affecting the function of the perfused kidney. Only high concentrations of DDA were shown to produce alterations in cellular function.