Effect of renal tubular damage on non-cancer mortality in the general Japanese population living in cadmium non-polluted areas

J Appl Toxicol. 2023 Dec;43(12):1849-1858. doi: 10.1002/jat.4518. Epub 2023 Jul 17.

Abstract

This study aimed to clarify the cause-effect relationship between renal tubular damage and non-cancer mortality in the general Japanese population. We conducted a 19-year cohort study including 1110 men and 1,03 women who lived in three cadmium-non-polluted areas in 1993 or 1994. Mortality risk ratios based on urinary β2-microglobulin (β2MG) and N-acetyl-β-glucosaminidase (NAG) concentrations were estimated for specific non-cancer diseases using the Fine and Gray competing risks regression model. In men, continuous urinary NAG (+1 μg/g cre) concentrations were significantly correlated with increased mortality caused by diseases of the respiratory system (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03-1.15). Urinary β2MG (+100 μg/g cre) concentrations were significantly correlated with increased mortalities caused by kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00-1.03), renal diseases (HR: 1.01, 95% CI: 1.00-1.03), renal failure (HR: 1.02, 95% CI: 1.00-1.03), and external causes of mortality (HR: 1.01, 95% CI: 1.00-1.02). In women, urinary NAG (+1 μg/g cre) concentrations were significantly associated with increased mortality caused by ischemic heart diseases (HR: 1.02, 95% CI: 1.00-1.04) and kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00-1.04). Urinary β2MG (+100 μg/g cre) concentrations were significantly correlated with increased mortality caused by cardiovascular diseases (HR: 1.01, 95%CI: 1.00-1.02), ischemic heart diseases (HR: 1.01, 95%CI: 1.00-1.02), and kidney and urinary tract diseases (HR: 1.02, 95% CI: 1.01-1.03). The present study indicates that renal tubular damage was significantly related to several non-cancer disease causes of mortality in Japan's general population living in cadmium-non-polluted areas.

Keywords: Fine and Gray competing risks regression model; cohort study; non-cancer mortality; renal dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / urine
  • Cadmium / toxicity
  • Cadmium / urine
  • Cohort Studies
  • East Asian People
  • Environmental Exposure / adverse effects
  • Environmental Exposure / analysis
  • Female
  • Humans
  • Kidney Diseases* / chemically induced
  • Kidney Diseases* / mortality
  • Kidney Diseases* / urine
  • Male
  • Myocardial Ischemia* / mortality
  • beta 2-Microglobulin / urine

Substances

  • Acetylglucosaminidase
  • beta 2-Microglobulin
  • Cadmium