Recent epidemiological studies on itai-itai disease as a chronic cadmium poisoning in Japan

Itai-itai disease is a chronic cadmium poisoning with renal tubular dysfunction followed by osteomalacia. Renal tubular dysfunction among inhabitants of the cadmium-polluted Jinzu River basin was irreversible and progressive, despite the fact that cadmium exposure had decreased. The bone mass was decreased in the inhabitants living in cadmium-polluted areas with renal tubular dysfunction, correlating with the urinary β2-microglobulin level. The decreased bone mass was diagnosed as latent renal tubular osteomalacia. Low serum erythropoietin levels were detected among the patients with itai-itai-disease, despite the presence of severe anemia. The anemia found in the end-stage of the disease was closely associated with an impaired renal function. Health surveys in cadmium-polluted areas of 8 prefectures were carried out, and many cases of renal tubular dysfunction were found in 4 prefectures, although the most severe cases were found in Toyama Prefecture. Many cases whose clinical features are completely in accord with those of itai-itai disease with severe renal tubular dysfunction and osteomalacia were reported in 3 prefectures as well as Toyama Prefecture. Mortality risks were increased in the patients with itai-itai disease, in the group suspected of having the disease, and in the groups of mild renal tubular dysfunction with 300–<1,000 μg/g creatinine. The development stage of the disease was divided into three stages. Those are the mild stage (stage of cadmium nephropathy) with the renal tubular dysfunction and decreased bone mass, the typical stage with the severe renal tubular dysfunction and pseudofracture detectable by X-ray examination, and the serious stage with severe renal dysfunction and pseudofracture and/or fracture.