The physiological determinants of low-level urine cadmium: an assessment in a cross-sectional study among schoolchildren

Background: Recent studies in children have reported associations of urinary cadmium (U-Cd), used as biomarker of Cd body burden, with renal dysfunction, retarded growth and impaired cognitive development in children. Little is known, however, about factors influencing U-Cd in children and likely to act as confounders. Methods: In a cross-sectional study involving 249 schoolchildren (mean age, 5.72 years; 138 boys), we measured the urine concentrations of cadmium, zinc, lead, albumin, alpha(1)-microglobulin (A1M), retinol-binding protein, beta(2)-microglobulin and club cell protein (CC16). Determinants of U-Cd expressed per creatinine or adjusted to specific gravity were identified by multiple regression analyses. Results: Girls and boys had similar median concentrations of U-Cd (0.22 and 0.24 mu g/L, 0.33 and 0.35 mu g/g creatinine, respectively). When models were run without including creatinine or specific gravity among independent variables, urinary zinc, urinary A1M and age emerged as the strongest predictors of U-Cd expressed per g creatinine or adjusted to SG. When adding creatinine among predictors, urinary creatinine emerged as an additional strong predictor correlating negatively with U-Cd per g creatinine. This strong residual influence of diuresis, not seen when adding specific gravity among predictors, linked U-Cd to U-A1M or U-CC16 through secondary associations mimicking those induced by Cd nephrotoxity. Conclusions: In young children U-Cd largely varies with diuresis, zinc metabolism and urinary A1M. These physiological determinants, unrelated to Cd body burden, may confound the child renal and developmental outcomes associated with low-level U-Cd.