Associations of urinary cadmium with age and urinary proteins: further evidence of physiological variations unrelated to metal accumulation and toxicity

Abstract

Background: The current risk assessment for environmental cadmium (Cd) largely relies on the assumption that urinary Cd (U-Cd) is a reliable biomarker of the Cd body burden. Recent studies have questioned the validity of this assumption.

Objectives: We studied the lifetime trend of U-Cd as a function of diuresis, gender, smoking status, and protein tubular reabsorption. We also analyzed the associations between U-Cd and urinary proteins.

Methods: Cd, retinol-binding protein, and albumin were measured in the urine of six cohorts of the general population of Belgium, with a mean age ranging from 5.7 to 88.1 years (n = 1,567). Variations of U-Cd with age were modeled using natural cubic splines.

Results: In both genders, U-Cd decreased to a minimum (~ 0.20 μg/L) at the end of adolescence, then increased until 60-70 years of age (~ 0.60 μg/L in never-smokers) before leveling off or decreasing. When U-Cd was expressed in micrograms per gram of creatinine, these variations were amplified (minimum, 0.15 µg/g creatinine; maximum, 0.70 µg/g creatinine) and much higher U-Cd values were observed in women. We observed no difference in U-Cd levels between never-smokers and former smokers, and the difference with current smokers did not increase over time. Lifetime curves of U-Cd were higher with increasing urinary retinol-binding protein or albumin, a consequence of the coexcretion of Cd with proteins.

Conclusions: At low Cd exposure levels, U-Cd and age are associated through nonlinear and nonmonotonic relationships that appear to be driven mainly by recent Cd intake and physiological variations in the excretion of creatinine and proteins.

Figure 1

Associations of U-Cd in µg/L (A) or µg/g creatinine (B) with age according to gender in healthy and non­smoking male (n = 405) and female (n = 581) participants. Data were fitted using natural cubic splines with four knots placed at the 20th, 40th, 60th, and 80th percentiles. Differences between males and females were statistically significant (p < 0.05) at ≥ 60 years of age in (A), and at ≥ 20 years of age in (B).

Figure 2

Associations of U-Cd in µg/L (A) or µg/g creatinine (B) with age according to smoking status. Data were fitted using natural cubic splines with three knots placed at the 25th, 50th and 75th percentiles. In adults 18–40 years of age, U-Cd of current and former smokers was significantly higher than that in never-smokers; however, after 40 years of age, the difference was statistically significant only between current and never-smokers. Never-smokers, n = 490; former smokers, n = 213; current smokers, n = 368.

Figure 3

Association between U-Cd and age by tertiles of U-RBP (A) and of U‑Alb (B) in the nonsmoking population (n = 840). Data were fitted using natural cubic splines with three knots placed at 25th, 50th and 75th percentiles. U-Cd values were significantly different between tertiles for U-RBP and U‑Alb from adolescence.