The renal toxicity of cadmium metallothionein: Morphometric and X-ray microanalytical studies

This report describes changes in the renal lysosome system of rabbits during a tubular nephropathy produced by a single intravenous injection of cadmium metallothionein at dosages of 0, 0.1, 0.2, or 0.4 mg of Cd/kg body weight. Pronounced light microscopic and ultrastructural changes in renal tubule cells which consisted of necrosis and sloughing were observed at the highest dose. Ultrastructural morphometry and X-ray microanalysis of tubule cells were evaluated in relation to renal function and tissue cadmium levels in the same animals. The most pronounced ultrastructural change in tubule cells of treated animals at all dosages was a highly significant dose-related increase in the volume density of lysosomes which were shown by X-ray microanalysis to contain cadmium. Minor changes were observed in the volume densities of tubule cell mitochondria, nuclei, and vacuoles. The findings were associated with dose-related increases in serum creatinine concentrations and decreases in urine creatinine concentrations. The above data are discussed in relation to tissue concentrations of cadmium and the role of lysosomes in renal tubular nephropathy produced by metal-binding proteins.