Hypoproduction of erythropoietin contributes to anemia in chronic cadmium intoxication: clinical study on Itai-itai disease in Japan

Arch Toxicol. 1994;68(10):632-6. doi: 10.1007/BF03208342.


Itai-itai disease is a condition caused by long-term exposure of the inhabitants of Toyama prefecture, Japan, to cadmium intoxication. The characteristic clinical features of this disease include renal tubular dysfunction, osteomalacia, and anemia. In order to clarify the pathogenesis of the anemia, the red blood cell count, hemoglobin concentration, hematocrit, serum iron level, total iron-binding capacity, serum ferritin level, serum erythropoietin level, creatinine clearance, fractional excretion of beta 2-microglobulin, and bone marrow morphology were determined in ten patients with Itai-itai disease. Low serum iron or ferritin levels were not observed, and bone marrow aspiration did not reveal any specific hematological disorders. A close relationship was observed between the decrease in the hemoglobin level and the progression of renal dysfunction. Low serum erythropoietin levels were detected despite the presence of severe anemia. These results suggest an important role of renal damage in the anemia which develops in Itai-itai disease.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia / chemically induced*
  • Blood Proteins / metabolism
  • Bone Marrow / drug effects
  • Bone Marrow Cells
  • Cadmium Poisoning* / complications
  • Erythrocyte Count / drug effects
  • Erythropoiesis / drug effects
  • Erythropoietin / biosynthesis*
  • Female
  • Ferritins / blood
  • Hematocrit
  • Hemoglobins / metabolism
  • Humans
  • Iron / blood
  • Japan
  • Kidney Glomerulus / drug effects
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Middle Aged
  • Osteomalacia / chemically induced
  • beta 2-Microglobulin / metabolism


  • Blood Proteins
  • Hemoglobins
  • beta 2-Microglobulin
  • Erythropoietin
  • Ferritins
  • Iron