DISCREPANCY BETWEEN THE NEPHROTOXIC POTENCIES OF CADMIUM-METALLOTHIONEIN AND CADMIUM CHLORIDE AND THE RENAL CONCENTRATION OF CADMIUM IN THEPROXIMAL CONVOLUTED TUBULES

Acute exposure to inorganic cadmium produces hepatotoxicity, but no re nal injury. In contrast, chronic exposure to Cd produces nephrotoxic e ffects. However, a single injection of cadmium bound to metallothionei n (CdMT) can produce nephrotoxicity similar to that seen with chronic exposure to Cd. It is generally thought that CdMT is nephrotoxic becau se more CdMT than CdCl2 distributes to the kidney. To test this hypoth esis, the toxic effects and distribution of Cd were compared after iv injection of CdMT and CdCl2 to mice. CdMT increased urinary excretion of glucose, and protein indicating renal injury. This dysfunction occu rred with dosages as low as 0.2 mg Cd/kg. In contrast, renal function was unaltered by CdCl2 administration, even at dosages as high as 3 mg Cd/kg. CdMT distributed almost exclusively to the kidney, whereas CdC l2 preferentially distributed to the liver. However, a high concentrat ion of Cd was also found in the kidneys after CdCl2 administration. In fact, the renal Cd concentration after administration of a high but n onnephrotoxic dose of CdCl2 was equal to or higher than that obtained after injection of nephrotoxic doses of CdMT. Light microscopic autora diography studies, using 0.3 mg Cd/kg as CdMT and 3 mg Cd/kg as CdCl2, indicated that Cd from CdMT preferentially distributed to the convolu ted segments (S1 and S2) of the proximal tubules, whereas Cd from CdCl 2 distributed equally to the various segments (convoluted and straight ) of the proximal tubules. However, the concentration of Cd at the sit e of nephrotoxicity, the proximal convoluted tubules, was higher after CdCl2 than after CdMT administration. A higher Cd concentration in bo th apical and basal parts of the proximal cells was found after CdCl2 than after CdMT administration. Therefore, the reason why CdMT is neph rotoxic and CdCl2 is not nephrotoxic is not due to a higher concentrat ion of Cd in the target cells after CdMT than after CdCl2 administrati on. (C) 1995 Academic Press, Inc.