Chronic exposure to low-level cadmium induced zinc-copper dysregulation.

BACKGROUND AND OBJECTIVES: Exposure to cadmium (Cd) has been associated with aberrant zinc and copper homeostasis. This study investigated if Cd exposure impairs renal reabsorption of metals. METHODS: Renal tubular reabsorption of metals were calculated from urine to serum metal ratios and analyzed for an independent association with Cd exposure levels, using data from 100 men and 100 women, aged 16-60 years. RESULTS: The smoking prevalence was 30% in men and 0% in women. The male and female means (SD) for urine Cd were 0.54 (0.43) and 0.62 (0.43) µg/g creatinine. The mean (SD) for fractional zinc reabsorption was 77.2 (23) % in men and 87.7 (13.3) % in women, while the copper reabsorption was 100% in both men and women. Lower zinc reabsorption levels were associated with higher Cd exposure (P<0.001), higher serum copper to zinc ratios (P=0.007) and higher tubular impairment levels (P=0.024). Reduced zinc reabsorption was particularly severe in smokers as those with high Cd exposure had 44.9% and 37.2% (P<0.001) lower zinc reabsorption than those with low and moderate exposures. The mean zinc reabsorption in male non-smokers with high Cd exposure was 25.8% (P<0.001) and 18.2% (P=0.003) lower than those with low and moderate exposures, while the corresponding figure for female non-smokers was 17% (P<0.001), and 12.8% (P=0.013), respectively. CONCLUSIONS: This is the first report demonstrating Cd-dose dependent reduction in renal zinc reabsorption and high serum copper to zinc ratios.