Correlation of cadmium-induced nephropathy and the metabolism of endogenous copper and zinc in rats.

Female Wistar rats were injected (sc) every second day for 8 weeks with Cd (0.25 mg/kg) as CdCl2. After only a 2-week exposure, when cadmium (Cd) concentration in liver was about 13 micrograms/g, ultrastructural examinations revealed some irregular ergastoplasm systems and significant proliferation of smooth endoplasmic reticulum in the hepatocyte ultrastructure. The increase in Zn content occurred simultaneously with the increase in Cd concentration in the liver (Zn to Cd ratio was 1:1). In the kidneys after a 3-week exposure, when Cd concentration was 7 micrograms/g, the concentration of endogenous Cu increased. At the same time the urinary excretion of that metal was considerably higher than that of the control group. In the kidneys after a 4-week exposure, when Cd concentration in this organ exceeded 10 micrograms/g tissue, injured brush border microvilli and swollen mitochondria in the proximal convoluted tubular cells were seen. In renal corpuscules, fusion between the podocyte pedicles was also found. The changes in renal cortex ultrastructure became more pronounced when Cd concentration in kidney was increasing. Necrotic changes in the examined organ were observed when Cd concentration increased to about 30 micrograms/g tissue. The critical concentration in renal cortex of about 200 micrograms/g tissue should be revised. The present margin of safety with regard to risk of renal effects is small.