Elevated Urinary Levels of Vitamin D-Binding Protein in the Inhabitants of a Cadmium Polluted Area, Jinzu River Basin, Japan

Abstract

Environmental cadmium (Cd) pollution and its effects on human health are still important issues. The most severe and representative manifestation of chronic Cd intoxication is Itai-itai disease, which is a syndrome that includes renal tubular dysfunction, osteomalacia, and generalized pain due to multiple bone fractures. The whole mechanism of how renal dysfunction relates to the development of bone lesions is unresolved. Vitamin D-binding protein (DBP) binds, transports and activates vitamin D, which plays a major role in calcium homeostasis and bone turnover. In this study, we measured urinary DBP levels and investigated their relationship to the markers of renal tubular dysfunction in the inhabitants of a Cd-polluted Jinzu River basin in Toyama Prefecture, Japan (Cd group). We also investigated age-matched subjects from an area known to have lower levels of Cd pollution (reference group). Urinary DBP was measured by a fluorometric enzyme-linked immunosorbent assay (ELISA), which was established in our laboratory. Significantly higher levels of urinary DBP were observed in the Cd group compared to the reference group. We observed significant positive correlations between urinary levels of DBP and renal tubular dysfunction markers in both groups. In the Cd group, urinary levels of DBP had a negative correlation with serum phosphate value. These results indicate that excretion of urinary DBP is increased after long-term Cd exposure and that the loss of DBP in urine may be linked to renal tubular dysfunction and possibly bone lesions in the inhabitants of Cd-polluted areas.