Recent Clinical and Epidemiological Studies of Itai-Itai Disease (Cadmium-Induced Renal Tubular Osteomalacia) and Cadmium Nephropathy in the Jinzu River Basin in Toyama Prefecture, Japan
The majority of studies on the biological effects of exposure to the heavy metal cadmium (Cd) have focused on the epidemiology, mechanisms of toxicity, pathophysiology, disease progression, and prognosis of multiple proximal tubular dysfunction (Cd nephropathy). Indeed, this was the earliest symptom to occur in the residents of the downstream Jinzu River basin in Toyama Prefecture, which was contaminated by Cd. Despite efforts to reduce Cd exposure through rice grown in private rice paddies and the replacement of contaminated rice paddy soil, Cd nephropathy has continued to persist in this area. In Cd nephropathy, even when the disease is relatively very mild with fractional excretion (FE) of β2-microglobulin (β2-MG) levels of <1 mg/g creatinine (Cr), FEs of uric acid, calcium, sodium, and chloride increase. The results of a 27-year observational study have indicated that cases presenting with urinary β2-MG levels of ≥10 mg/g Cr have decreased tubular reabsorption of phosphate, decreased glomerular filtration rates (GFRs), and anemia with Cd nephropathy observed at GFRs of <30 mL/min. In addition, as recent as 2015, one case with urinary β2-MG levels of ≥10 mg/g Cr developed osteomalacia and was officially certified as having itai-itai disease. Fibroblast growth factor 23 is not involved in the pathogenesis of hypophosphatemia in itai-itai disease and Cd nephropathy.
KeywordsChronic cadmium poisoning Fibroblast growth factor 23 Hypophosphatemia Itai-itai disease β2-microglobulin Multiple proximal tubular dysfunction Osteomalacia
The research results covered in the present paper include the results of the “Study on the health effects of environmental exposure to cadmium in the residents of cadmium-contaminated Jinzu River basin” (principal investigator: Keiko Aoshima), which were parts of the 2012 and 2016 Studies of the Health Effects of Heavy Metals organized by the Ministry of the Environment, Japan.
Conflict of Interest
The author has no conflict of interest to declare.
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