Shifts in the dose-effect relationship for the nephropathy induced by cadmium-metallothionein in rats after a reduction in renal mass.

The aim of the present study was to determine if a reduction of renal mass altered the dose-effect relationship for the nephropathy induced by cadmium-metallothionein. Uninephrectomized (NPX) and sham-operated (SO) rats were given a single i.v. injection of cadmium-metallothionein at a dose of 0.1, 0.2 or 0.3 mg of cadmium per kg, and were sacrificed 24 hr after the injection. Quantitative computerized morphometric analysis of sections of kidney, plasma creatinine and the urinary excretion of some cellular enzymes and plasma solutes were used to evaluate the severity of renal injury at each dose of cadmium-metallothionein. No renal injury was detected in either the NPX or SO rats given the lowest dose of cadmium-metallothionein. At the middle dose of cadmium-metallothionein, renal injury occurred in both the NPX and SO rats, but the severity of injury was substantially greater in the NPX rats. This increased renal injury in the NPX rats correlated with increased renal content of cadmium and increased urinary excretion of cadmium. At the highest dose of cadmium-metallothionein, renal injury was quite severe. Some of the data show that renal injury was more severe in the NPX rats than in the SO rats. In summary, our findings indicate that there is a shift to the left in the dose effect relationship in the nephropathy induced by cadmium-metallothionein. The mechanism for this shift is not known at present, although it appears to be related, in part, to increased renal accumulation and/or retention of cadmium.