LONG-TERM CADMIUM EXPOSURE INDUCES ANEMIA IN RATS THROUGH HYPOINDUCTION OF ERYTHROPOIETIN IN THE KIDNEYS

Cadmium (Cd), a highly toxic heavy metal, is distributed widely ill th e general environment of today. The characteristic clinical manifestat ions of chronic Cd intoxication include renal proximal tubular dysfunc tion, general osteomalacia with severe pains, and anemia. We have rece ntly reported that the serum level of erythropoietin (EPO) remained lo w despite the severe anemia in patients with Itai-itai disease, the mo st severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd t o rats for a long period and performed the analysis of EPO mRNA induci bility in the kidneys. The rats administered Cd for 6 and 9 months sho wed anemia with low levels of plasma EPO as well as biochemical and hi stological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells.