Kidney cadmium levels and associations with urinary calcium and bone mineral density: a cross-sectional study in Sweden

Background: Cadmium (Cd) can cause renal damage and osteoporosis after high-level exposure. Recently such effects, including increased urinary excretion of calcium, have been shown also at low-level exposure, as measured by Cd in blood or urine. However, associations with kidney Cd have not been examined. The aim of this study was to explore the relation between kidney Cd and urinary calcium excretion, or bone mineral density. Methods: Cd was determined in kidney cortex biopsies from 109 living kidney donors. Serum was analyzed for ionized calcium, parathyroid hormone and vitamin D. Calcium was analyzed in overnight and 24-hour urine samples. Bone mineral density was measured in a subgroup of 67 donors. Associations between single variables were assessed by Spearman and Pearson correlation coefficients. Differences between independent groups were compared using Student's t-test. For related samples, paired t-test was applied. Associations between urinary calcium and kidney Cd, ionized serum calcium, serum parathyroid hormone, inactive and active vitamin D and background variables were assessed using multiple linear regression and logistic regression. Results: In spite of relatively low kidney Cd levels (median 13 mu g/g, range 1.5-55 mu g/g) kidney Cd and urinary calcium were positively associated, mainly caused by an association in women. Donors with kidney Cd above the median (subgroup mean 23 mu g/g) had significantly higher excretion of urinary calcium normalized for creatinine than those below the median (subgroup mean 7.3 mu g/g). In women, also the excretion of Ca per hour was higher in those with high kidney Cd (24 hour sample mean 0.21 vs. 0.15 mmol/h; overnight sample 0.16 vs. 0.11 mmol/h). There were negative associations between kidney Cd and bone mineral density, most of which, however, disappeared in multivariate analyses. Conclusions: This study provides support for an association between kidney Cd levels and urinary calcium excretion in women, but not in men. The results strengthen the case for preventive measures against Cd pollution.