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Epidemiology
Research
Causes of death in patients with Itai-itai disease suffering from severe chronic cadmium poisoning: a nested case–control analysis of a follow-up study in Japan
  1. Muneko Nishijo1,2,
  2. Hideaki Nakagawa3,
  3. Yasushi Suwazono4,
  4. Kazuhiro Nogawa4,
  5. Teruhiko Kido5
  1. 1 Department of Public Health, Kanazawa Medical University, Uchinada, Ishikawa, Japan
  2. 2 Health Evaluation Center, Kanazawa Medical University Hospital, Uchinada, Ishikawa, Japan
  3. 3 Institute of Medical Science, Kanazawa Medical University, Uchinada, Ishikawa, Japan
  4. 4 Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
  5. 5 Department of Community Health Nursing, School of Health Sciences, Kanazawa University, Kanazawa, Japan
  1. Correspondence to Dr Muneko Nishijo; ni-koei{at}kanazawa-med.ac.jp

Abstract

Objective To clarify the causes of deaths among patients with Itai-itai disease and severe cadmium (Cd) poisoning.

Design Nested case–control analysis of a population-based cohort study.

Setting Database of patients with Itai-itai disease and residents of Cd-polluted areas, maintained by the Ministry of Environment, Japan.

Participants Subjects included 142 women with Itai-itai disease, 111 women with Cd-induced renal tubular dysfunction and 253 controls matched for sex, age and occupation. All subjects participated in a health impact survey between 1979 and 1984 and were followed until 30 November 2005.

Main outcomes and measures Adjusted HRs with 95% CIs for cause of death in women with Itai-itai disease and screened female cases with tubular dysfunction were compared with matched pair controls, using Cox’s proportional hazard model. Vital statistics data were used to determine cause of death. Direct causes of death from autopsy records were used in 29 patients who died from Cd poisoning.

Results The most common cause of death among patients with Itai-itai disease was pneumonia, with a significantly increased adjusted HR of 4.54 (95% CI 2.65 to 7.76). Renal diseases were the most common cause of death in renal tubular dysfunction cases, with an increased HR of 12.0 (95% CI 3.92 to 36.8). The adjusted HR for renal diseases was also significantly increased in patients with Itai-itai disease (19.49 (95% CI 6.43 to 59.09)), with a greater impact on mortality of patients with Itai-itai disease than screened cases. The HR for gastrointestinal (GI) diseases was significantly increased (13.79 (95% CI 3.87 to 49.10)) in patients, especially in the first 10 years (37.1 (4.81 to 286.0)).

Conclusions Among patients with Itai-itai disease, pneumonia and GI diseases contributed to increased mortality risk. Renal disease is also a significant mortality risk in patients with Itai-itai disease and women with renal tubular dysfunction.

  • causes of death
  • cadmium poisoning
  • autopsy
  • a follow-up study

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjopen-2016-015694

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    Footnotes

    • Contributors MN and HN participated in the design and coordination of the study. MN, KN and TK carried out the survey for baseline data collection and preparation of survival data. HN and YS performed the statistical analysis. MN and HN prepared the draft for the manuscript. All authors read and approved the final manuscript. All authors contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript.

    • Funding This work was supported by grant for aids from Agency of Environment for Health effects due to Heavy Metal exposure 2009-12 and 2013-15. The funder has no role in: the study design; the collection, analysis or interpretation of data; the writing of the report or in the decision to submit the article for publication.

    • Competing interests None declared.

    • Patient consent Impossible consent

    • Ethics approval The study protocol was approved by the institutional review boards of the Kanazawa Medical University, Japan (registration no. 212).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement We have no data for sharing.