Effects of aging on cadmium and tubular dysfunction markers in urine from adult women in non-polluted areas

Objectives: The objectives of the present analyses were to examine if Cd and tubular dysfunction marker levels in urine show age-dependent changes among women who lived in areas with no known cadmium (Cd) pollution in Japan, and if the trends would be further modified by correction of analyte concentration in terms of urinary creatinine (CR or cr) or urine specific gravity (SG or sg). Methods: The results of urinalysis for Cd, alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), and N-acetyl-beta-D-glucosaminidase (NAG) concentrations together with CR and SG were cited from previously established databases. A majority of urine samples were collected in 2000-2002 from adult women (mostly at 40-60 years of age) in various areas in Japan, and the collection was supplemented by cases of >= 60-year-old women in 2003. In total, 11,090 never-smoking cases were subjected to statistical analysis. The values as observed (e.g., Cd-ob), together with after correction for CR (e.g., Cd-cr) or SG (e.g., Cd-sg), were examined by linear regression analysis after logarithmic conversion. Results: The geometric mean (GM) values for Cd were 1.10 mu g/l (as observed) or 1.32 mu g/g cr (after correction for creatinine concentration). No increases were found in the levels of alpha(1)-MG, beta(2)-MG or NAG on a group basis, in agreement with the conditions that there was no known environmental pollution with Cd in the sampling areas. There were almost linear increases in logarithm of Cd, alpha(1)-MG, beta(2)-MG and NAG concentrations as age advanced. As CR, and to a lesser extent SG, also decreases steadily throughout life (Ikeda et al. 2005; Moriguchi et al. 2005), the correction of the analyte concentrations for urine density induced substantial increases in the analyte values; i.e., the correction by CR and SG induced amplification of the increases by two- and 1.4-times, respectively, compared with the increase in non-corrected observed values. Conclusions: There were age-related increases in Cd and tubular dysfunction markers in urine among women in areas with no known Cd pollution. The increase was amplified two- or 1.4-times when CR or SG correction was applied, respectively. The observation suggests that care should be practiced in applying CR or SG correction, especially when evaluation of Cd exposure and resulting health effects is made among elderly populations.