Studies of cadmium uptake and metabolism by the kidney.

Our investigation was centered on a possible relationship between the toxicity of cadmium and changes in its chemical forms in tissues. Two models have been studied: one is the renal damage induced by a single injection of cadmium-containing metallothionein and the other is the renal damage induced by repeated injections of cadmium salt. Parenteral loading of cadmium-containing metallothionein caused acute and transitory necrotic damage of renal tubular lining cells. This was explained by the selective and rapid uptake of metallothionein at the proximal tubules and degradation of the protein, resulting in liberation of cadmium ions. Cadmium ions were injected repeatedly into rats, and the changes in the chemical forms of cadmium, zinc and copper in the liver and kidneys were correlated with the histological observations. The transitory necrotic damage of the proximal tubules caused during the repeated injections of cadmium was accompanied with a rapid decrease of the copper content in the kidney metallothionein. Further loading of cadmium ions induced increases in the amounts of cadmium not bound to metallothionein and its oxidation products as well as an increase of the Cd/Zn ratio in metallothionein. With these changes in the chemical forms of cadmium, persistent damage of the kidneys occurred. The transitory renal damage caused both by a single injection of cadmium-containing metallothionein and by repeated injections of cadmium salt can be explained by a limit of the native biosynthetic capacity of metallothionein in the kidney, while the persistent damage appears to be due to a limit of the induced capacity.