The effects of low doses of cadmium-metallothionein on the renal uptake of beta 2-microglobulin in rats.

The urinary excretion of beta 2-microglobulin (beta 2-m) was followed up in rats given increasing intravenous doses (15, 30, or 60 micrograms Cd/kg) of rat hepatic cadmium-metallothionein (Cd-MT). At the two highest doses, Cd-MT was found to induce two peaks in the urinary excretion of rat beta 2-m: a first narrow peak occurring immediately after the injection, followed 20 hr later by a broader peak. While the latter peak is caused by the well-known tubular toxicity of Cd-MT, the former most likely results from competition between rat Cd-MT and beta 2-m for a common renal transport system. This explanation is supported by the fact that the renal accumulation of MT-bound Cd can be inhibited by human beta 2-m. The Cd concentration in renal cortex of rats challenged with the lowest tubulotoxic dose of Cd-MT was only 3.4 ppm 4 hr following the injection. Since the Cd-MT nephrotoxicity is caused by the non-MT-bound Cd, which at this time represents about 70% of the renal Cd, it can be tentatively estimated that the critical concentration of free Cd in renal cortex is only 2 ppm, i.e., about 100 times less than the currently accepted critical value for the total concentration of this metal in kidney cortex.