Cadmium: exposure markers as predictors of nephrotoxic effects

Cadmium (Cd) is a cumulative element with a biological half-life of > 10 years in humans. The total amount of Cd accumulated in the liver and in the kidney can be measured in vivo by neutron activation (or x-ray fluorescence), but this technique does not necessarily measure the fraction that is biologically active. At low exposure (i.e., general environmental exposure or moderate occupational exposure), blood Cd is mainly influenced by the last 2 to 3 months of exposure. Under such conditions, the Cd concentration in urine mainly reflects the amount of Cd stored in the body, particularly in the kidney. In Europe and the US, the Cd reference values are usually < 2 nmol/mmol creatinine. Because most of the Cd in urine is probably bound to metallothionein, the changes in the urinary metallothionein concentration parallel those of Cd. The determination of Cd concentration in hair is of limited value because in humans it is difficult to distinguish between externally deposited and endogenous Cd. Fecal Cd is a good indicator of the oral daily intake. The results of several cross-sectional epidemiologic studies of the relation between the prevalence of renal dysfunction and Cd concentration in urine led us to propose a biological limit value for Cd of 5 and 2 nmol/mmol creatine for adult male workers and the general population, respectively.