Phlebotomy increases cadmium uptake in hemochromatosis

The intestinal absorption of the nephrotoxic environmental pollutant cadmiu m increases markedly when iron stores are depleted. This may be mediated by an up regulation of the recently identified mucosal transporter DMT1 (Nram p2 or DCT1) for divalent cations. We tested whether the highly increased ir on absorption in hereditary hemochromatosis (HH) was accompanied by an enha nced absorption of cadmium and lead. Cadmium and lead in blood and iron sta tus markers were determined in 21 nonsmoking subjects with HH genetically t ested for the HFE mutations and in 21 nonsmoking controls matched for age a nd sex. In subjects with HH on maintenance phlebotomy treatment, blood conc entrations of cadmium, but not lead, were significantly higher than in pair ed controls. There was a strong age-independent positive association betwee n blood cadmium and the number of years of phlebotomy treatment. Blood lead showed a similar bur less pronounced consequence of treatment. All HH subj ects with lower blood cadmium than the corresponding controls had either no mutation in the HFE gene, were not phlebotomized, or were phlebotomized fo r only a limited time. Our findings indicate that the treatment rather than the disease increased the cadmium uptake in homozygous HH. Further studies are needed to confirm whether the disease decreased cadmium absorption and whether the absorption was dependent on the genotype.