Relationship between urinary β₂‐microglobulin concentration and mortality in a cadmium‐polluted area in Japan: A 35‐year follow‐up study

Abstract

The relationship between urinary β 2-microglobulin (β 2-MG) and the risk of all-cause mortality and cause-specific mortality in a cadmium (Cd)-polluted area was investigated in 3139 inhabitants (1404 men and 1735 women) of the Kakehashi River basin in Japan at 35-year follow-up. The subjects had been participants in the 1981-1982 health impact survey that assessed Cd-induced renal dysfunction, as measured by the urinary β 2-MG concentration. Hazard ratios were calculated to assess the risk of all-cause and cause-specific mortality according to the urinary β 2-MG concentrations. Risk ratios (RRs) were assessed using the Fine and Gray regression model to account for competing risks of cause-specific mortality. The mortality rate was significantly higher in participants with urinary β 2-MG concentrations >1000 μg/g creatinine (Cr) for men and >300 μg/g Cr for women. In the proportional hazard model, higher urinary β 2-MG concentrations were associated with higher risks of circulatory disease, digestive system diseases, and kidney and urinary tract diseases in men and women, and with senility for women. However, when competing risk was accounted for, the RRs were significantly higher only for kidney and urinary tract diseases in men and women (RR for each increment of 1000 μg/g Cr [95% confidence interval]: 1.02 [1.00-1.04] for men, and 1.01 [1.00-1.02] for women). The long-term prognosis of participants with renal tubular dysfunction was poor, most likely due to kidney and renal tract diseases.

The Relationship between the Urinary Cadmium Concentration and Cause-Specific Mortality in Subjects without Severe Renal Damage: A 35-Year Follow-Up Study in a Cadmium-Polluted Area of Japan

“…The results showed that the urinary Cd concentration was significantly associated with mortality from heart failure in women and from diseases of the digestive system in men, even after adjustment for other causes of death using the Fine and Gray competing risk regression model. We previously reported that the urinary β2-MG concentration was associated with a high risk of mortality from renal disease, but not from other causes, in both men and women of the present cohort, as revealed by a competing risk model [8]. The kidney is a target of external Cd, and renal tubular dysfunction is the most prevalent adverse health effect induced by Cd exposure.…”

“…On the other hand, no significant association was observed between Cd exposure and any cause-specific mortality in participants with severe renal tubular dysfunction. We previously reported that the urinary concentration of β2-MG, a marker of renal tubular dysfunction, was associated with all-cause mortality as well as renal disease-specific mortality in inhabitants of a Cd-polluted area [8]. Renal tubular dysfunction may directly increase the risk of death from renal disease regardless of Cd exposure, suggesting that Cd is not associated with death in participants with severe renal damage.…”

“…Detailed information on the study population has been published previously [4,7,8,18]. In brief, a total of 3178 inhabitants (1424 men and 1754 women) of the Cd-polluted Kakehashi River basin who participated in the health impact survey in 1981-1982 were targeted in the present study.…”

“…At the 15-and 22-year follow-ups, the subjects with higher urinary Cd concentrations exhibited increased rates of all-cause mortality as well as mortality due to renal disease and heart failure [4,6]. Recently, we evaluated the risks of all-cause and cause-specific mortalities in inhabitants of the Kakehashi River basin, in a follow-up after 25 years, and reported that the urinary concentrations of Cd and beta 2-microglobulin (β2-MG) (a marker of renal tubular dysfunction induced by Cd exposure) were associated with higher risks of all-cause mortality and mortality due to renal disease [7,8]. We reported that [9] the standard mortality rates (SMRs) for all-cause of participants with a urinary β2-MG of ≥1000 mg/g Cr were significantly higher (127 for men and 146 for women) than for the Japanese general population.…”

Current Levels of Environmental Exposure to Cadmium in Industrialized Countries as a Risk Factor for Kidney Damage in the General Population: A Comprehensive Review of Available Data

“…A concentration of β2-MG exceeding 300 µg/g creatinine in the urine indicates defective tubular reabsorption [25]. Damage of this degree increases the risk of death due to kidney and urinary tract diseases [150]. Numerous studies have shown that the concentration of β2-MG in the urine rises with increasing exposure to Cd and an increasing concentration of this xenobiotic in the urine [9,37,40,45,145,151,152].…”