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 %, 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.
- 1.Friberg L, Piscator M, Nordberg GF, Kjellstrom T. Health effects of cadmium in the general environment in Japan. In: Cadmium in the environment. 2nd ed. Cleveland: Chemical Rubber Press; 1974. p. 137–227.Google Scholar
- 2.World Health Organization (WHO). Environmental health criteria 134. Cadmium. Geneva: WHO; 1992.Google Scholar
- 3.Nogawa K. Itai-itai disease and follow-up studies. In: Nriagu JO, editor. Cadmium in the environment, part II. New York: John Wiley & Sons; 1981. p. 643–89.Google Scholar
- 8.Kinyobinews (January 24, 2014). http://www.kinyobi.co.jp/kinyobinews/2014/01/24. Accessed 17 Sept 2017.
- 9.Nakagawa S. A study of osteomalacia in Toyama prefecture (so-called itai-itai disease). Ser Department Science, Kanazawa Univ Med Sch. 1960;56:1–51. (in Japanese with English summary)Google Scholar
- 10.Ministry of the Environment. Report on cadmium contaminated area resident health impact study committee; 2009 (in Japanese)Google Scholar
- 11.Wedeen RP, De Broe ME. Nephrotoxic metals. In: Davison AM, Cameron JS, Grunfeld JP, Ponticelli C, Ritz E, Winearls CG, et al., editors. Oxford textbook of clinical nephrology. 3rd ed. Oxford: Oxford University Press; 2005. p. 1075–89.Google Scholar
- 13.Brewer ED. The Fanconi syndrome. In: Gonick HC, Buckalew Jr VM, editors. Renal tubular disorders. New York: Marcel Dekker; 1985. p. 475–544.Google Scholar
- 14.Van’t Hoff WG. Fanconi syndrome. In: Davison AM, Cameron JS, Grunfeld JP, Ponticelli C, Ritz E, Winearls CG, et al., editors. Oxford textbook of clinical nephrology. 3rd ed. Oxford: Oxford University Press; 2005. p. 961–73.Google Scholar
- 18.Fan J, Aoshima K, Katoh T, Teranishi H, Kasuya M. A follow-up study on renal tubular dysfunction in women living in the cadmium-polluted Jinzu River basin in Toyama, Japan: part 1. Changes in the level of exposure to cadmium after soil replacement of polluted paddy fields and the related effects on the prognosis of renal tubular dysfunction. Jpn J Hyg. 1998;53:545–57. (in Japanese with English abstract)CrossRefGoogle Scholar
- 20.Aoshima K, Katoh T, Kasuya M. Renal tubular function and bone metabolism in inhabitants of the cadmium-polluted Jinzu river basin in Toyama Prefecture, Japan: a 27-year follow-up study of 17 women with β2-microglobulinuria. The 2012 Ministry of the Environment commissioned study report: General research on the relation between itai-itai disease and chronic cadmium poisoning; 2013. p. 47–63. (in Japanese with English summary)Google Scholar
- 21.Aoshima K, Ogura Y. Itai-itai disease and kidneys: epidemiology, pathophysiology and clinical course in multiple proximal tubular dysfunction induced by environmental exposure to cadmium. Kidney Metab Bone Dis. 2016;29:332–40. (in Japanese with English summary)Google Scholar