SOME EFFECTS OF URANYL ACETATE ON PROXIMAL TUBULAR FUNCTION IN RABBIT KIDNEY

Acute renal failure was studied in rabbits 2 days after the intravenous injection of uranyl acetate (0.2 mg uranium per kilogram body weight). The poisoned animals showed a decreased inulin clearance and even greater inhibition of mannitol and creatinine clearances. This finding implicates back-diffusion of tubular contents as a factor possibly contributing to the observed depression of glomerular filtration rate. Tubular function as measured by Tmg and TmPAH showed even more complete inhibition than glomerular function, indicating a cytotoxic effect on the renal tubule. Analysis of transport kinetics in tissues from poisoned animals in vitro permitted the localization of the major lesion in the PAH secreting system at the peritubular membrane. Efflux of PAH from cells into tubular lumen appeared unaffected. In agreement with the reduced PAH transport into cells, yet unchanged efflux from cells, the intracellular accumulation of PAH in vivo was grossly inhibited. Some implications of these findings for the mechanism of attack of uranium on the renal tubule are discussed. © 1968.