From THE INSTITUTE OF ENVIRONMENTAL MEDICINE Karolinska Institutet, Stockholm, Sweden CADMIUM EXPOSURE AND RISK OF KIDNEY EFFECTS AND BONE FRACTURES: POPULATION-BASED STUDIES IN ENGLAND AND SWEDEN

Cadmium (Cd) is a toxic metal with no beneficial biological function. The dissemination of cadmium to the surface environment, by industrial and agricultural practices, has led to increased human exposure. Food is the main source of exposure in the general non-smoking population however in areas close to industrial sources, contact with contaminated environmental media may also be important. Previous studies have shown toxic effects of cadmium on the kidneys and bone, however, considerable uncertainty remains over the exposure levels at which these toxic effects may start to occur and the clinical relevance of the early effects observed following long-term, low-level cadmium exposure. The aims of this thesis were: 1) To assess cadmium body burden and early signs of kidney dysfunction in a population exposed to industrial cadmium emissions and to develop and validate an air dispersion model of these emissions. 2) To identify urinary metabolites, associated with cadmium exposure, using metabolic profiling techniques. 3) To prospectively assess the association between validated estimates of dietary cadmium exposure and chronic kidney disease (CKD) incidence, kidney stone incidence, and fracture incidence, in two large population-based cohorts of men and