Correlation of parameters of cadmium exposure with onset of cadmium-induced nephropathy in rats.

Rats were injected daily, five days/week, with 0.6 mg Cd/kg as CdCl2 for eight weeks. Groups of rats were sacrificed weekly. Urine, plasma and tissue cadmium levels, and morphology of renal cortex were studied. No abnormal effects were found until the fifth or sixth week when cadmium in kidney reached about 100 micrograms/g tissue. At this time, renal tubular lining cells showed an increase in lysosomes, microbodies and smooth endoplasmic reticulum and a low molecular weight cadmium-binding species was detectable in plasma. These changes were followed by the onset of glycosuria and proteinuria, accompanied by abnormal mitochondrial morphology. This progressed to cellular swelling and finally necrosis at the seventh and eighth weeks when cadmium concentration of the kidney reached about 200 micrograms/g of tissue. It is concluded that there are two phases in the development of cadmium induced nephropathy. Phase I is an adaptive phase characterized by some increase in smooth endoplasmic reticulum, microbodies and secondary lysosomes and the presence of metallothionein intracellularly in liver and kidney, but no detectable metallothionein in plasma and no increase in urinary cadmium. Phase II is a toxic phase characterized by detectable low molecular weight cadmium-binding species in plasma and evidence of renal tubular dysfunction followed by lethal injury to renal tubular lining cells.