Cadmium, mercury, and lead in kidney cortex are not associated with urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in living kidney donors

Abstract

Cadmium in urine is positively associated with urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) concentrations, a sensitive marker of oxidative DNA damage. We determined whether kidney concentrations of cadmium, mercury, and lead, which may generate oxidative DNA damage, were associated with urinary 8-oxodG or not. 8-OxodG was measured in separate 24 h and overnight urine samples from Swedish healthy adult kidney donors (N = 152) using LC-MS/MS. Concentrations of metals were measured in kidney biopsies (N = 109) by ICP-MS. The median 8-oxodG concentrations (adjusted to specific gravity) in 24 h and overnight samples were 13.5 and 15.3 nmol/L; 8-oxodG excretion rates in 24 h and overnight samples were 0.93 and 0.86 nmol/h. In multivariable linear regression analyses, we did not find any association between 8-oxodG concentrations or rates and elements in the kidney. The 24-h 8-oxodG concentrations were positively associated with serum ferritin (β = 0.048, p < 0.0001), body weight (β = 0.13, p = 0.0019), and inversely with gender (β = -3.34, p = 0.0024). Similar associations with 8-oxodG excretion rates were stronger. Smoking was positively associated with 24-h 8-oxodG excretion rates (β = 0.26, p = 0.0090), but not with overnight samples. Neither cadmium, nor mercury or lead in the kidney contributed to urinary 8-oxodG concentrations in non-occupationally exposed subjects. The iron status was positively associated with urinary 8-oxodG, particularly in women.