No clear-cut evidence for cadmium-induced renal tubular dysfunction among over 10,000 women in the Japanese general population: a nationwide large-scale survey.
ABSTRACT To examine whether environmental exposure to cadmium has been inducing kidney dysfunction among middle-aged women in the general population in Japan.
This study was conducted in 2000 and 2001. Morning spot urine samples were collected from 10,753 women (mostly aged 35 to 60 years) in ten prefectures all over Japan (thus about 1,000 women per site). Urine samples were analyzed for cadmium (Cd-U), calcium (Ca-U), magnesium (Mg-U), zinc (Zn-U), alpha(1)- and beta(2)-microglobulins (alpha(1)- and beta(2)-MG-U). The urinary analyte concentrations were corrected for creatinine (cr) concentration (i.e., Ucr). The data thus obtained were subjected to statistical evaluation by chi-square test, ANOVA, multiple comparison test, and simple regression analysis (SRA) as well as multiple regression analysis (MRA) including logistic regression analysis (LRA). Log-normal distribution was assumed for Cd-Ucr, alpha(1)-MG-Ucr and beta(2)-MG-Ucr, whereas normal distribution was considered for age, Ca-Ucr, Mg-Ucr and Zn-Ucr.
Geometric mean values (GM) of Cd-Ucr were distributed unevenly, depending on the sampling areas, with a grand GM of 1.3 microg/g cr, the highest (3.2 microg/g cr) and lowest GM values(0.8 microg/g cr) being significantly different from GMs of other areas. Correlation matrix analysis with subjects of all ages showed that log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr correlated significantly (r=0.272 and 0.202, respectively) with log Cd-Ucr, but they correlated also with age (r=0.280 and 0.213, respectively). The same analysis with the two selected age groups (41-50 and 51-60 years), however, failed to show close correlation of alpha(1)-MG-Ucr and log beta(2)-MG-Ucr with Cd-Ucr. Both MRA and LRA indicated that age was a confounding factor in the evaluation of the effect of Cd-U on the two MG levels. Whereas the LRA with the all-age group showed a positive influence of log Cd-Ucr on log alpha(1)-MG-Ucr and log beta(2)-MG-Ucr, such effect disappeared in parallel with the disappearance of age effects when LRA was conducted with the two selected age groups. An exceptional observation was the influence of log Cd-Ucr on log alpha(1)-MG-Ucr (but not on log beta(2)-MG-Ucr) in LRA when a cut-off value of 5.00 mg for alpha(1)-MG-U/g cr was applied. Comparison between the low and high Cd-U groups showed that both alpha(1)-MG-Ucr and beta(2)-MG-Ucr were higher in the high Cd-U groups, but prevalence of cases with alpha(1)-MG-Ucr and beta(2)-MG-Ucr in excess of the cut-off values did not differ between the two groups except when a cut-off value of 5.00 mg/g cr was employed for alpha(1)-MG-U.
In over-all evaluation, no clear-cut evidence was obtained in the present study to show that environmental exposure to Cd has induced tubule dysfunction among middle-aged women in the general population in Japan. It might be the case, however, that an increase in alpha(1)-MG-U was associated with Cd exposure. In this sense, it is apparently desirable from public health viewpoints to make further efforts to reduce the intensity of the general population's exposure to environmental Cd.
Article: Cadmium osteotoxicity in experimental animals: mechanisms and relationship to human exposures.[show abstract] [hide abstract]
ABSTRACT: Extensive epidemiological studies have recently demonstrated increased cadmium exposure correlating significantly with decreased bone mineral density and increased fracture incidence in humans at lower exposure levels than ever before evaluated. Studies in experimental animals have addressed whether very low concentrations of dietary cadmium can negatively impact the skeleton. This overview evaluates results in experimental animals regarding mechanisms of action on bone and the application of these results to humans. Results demonstrate that long-term dietary exposures in rats, at levels corresponding to environmental exposures in humans, result in increased skeletal fragility and decreased mineral density. Cadmium-induced demineralization begins soon after exposure, within 24 h of an oral dose to mice. In bone culture systems, cadmium at low concentrations acts directly on bone cells to cause both decreases in bone formation and increases in bone resorption, independent of its effects on kidney, intestine, or circulating hormone concentrations. Results from gene expression microarray and gene knock-out mouse models provide insight into mechanisms by which cadmium may affect bone. Application of the results to humans is considered with respect to cigarette smoke exposure pathways and direct vs. indirect effects of cadmium. Clearly, understanding the mechanism(s) by which cadmium causes bone loss in experimental animals will provide insight into its diverse effects in humans. Preventing bone loss is critical to maintaining an active, independent lifestyle, particularly among elderly persons. Identifying environmental factors such as cadmium that contribute to increased fractures in humans is an important undertaking and a first step to prevention.Toxicology and Applied Pharmacology 06/2009; 238(3):258-65. · 4.45 Impact Factor
Article: Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006.[show abstract] [hide abstract]
ABSTRACT: Environmental factors have been associated with the outbreak of chronic kidney disease (CKD). We evaluated the association of Cadmium (Cd) exposure with the risk of CKD in U.S. adults who participated in the 1999-2006 National Health and Nutrition Examination Surveys (NHANES). 5426 subjects > or = 20 years were stratified for values of urinary and blood Cd and a multivariate logistic regression was performed to test the association between blood and urinary Cd, CKD and albuminuria (ALB) after adjustment for age, gender, race/ethnicity, body mass index and smoking habits. Subjects with urinary Cd > 1 mcg/g and subjects with blood Cd > 1 mcg/L showed a higher association with ALB (OR 1.63, 95% CI 1.23, 2.16; P = 0.001). Subjects with blood Cd > 1 mcg/L showed a higher association with both CKD (OR 1.48, 95% CI 1.01, 2.17; P = 0.046) and ALB (OR 1.41, 95% CI 1.10, 1.82; P = 0.007). An interaction effect on ALB was found for high levels of urinary and blood Cd (P = 0.014). Moderately high levels of urinary and blood Cd are associated with a higher proportion of CKD and ALB in the United States population.BMC Public Health 01/2010; 10:304. · 2.00 Impact Factor