[Long-term effect of cadmium exposure on residents' renal dysfunction: An epidemiologic study].

OBJECTIVE: To study long-term effect on renal function exposed to environmental cadmium. METHODS: Stratified random sampling and cluster sampling method of epidemiological investigations were carried out in northern Guangdong province between April, 2011 and August, 2012. A total of 167 residents who lived in high cadmium exposure area for more than 15 years, aged above 40 were selected in exposed group. Moreover, A total of 145 residents who had similar living and economic conditions and lived in local for more than 15 years, aged above 40 were selected in control group. We used health questionnaires and medical examinations in order to acquire their health status. Home-harvested rice and vegetables were collected using quartering method for detection of cadmium level. Urine specimens of residents were collected for detection of cadmium level and creatinine as well as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase (NAG), ß2-microglobulin (ß2-MG), and retinol binding protein(RBP), respectively. The analysis of spearman rank correlation and multiple regression were used to investigate the relationships between age, urinary cadmium levels and renal injury biomarkers. RESULTS: The cadmium levels in rice and vegetables of exposed group were 0.75 and 0.10 mg/kg, both were significantly higher than 0.07 and 0.01 mg/kg in the control group (Z values were -6.32 and -7.84, all P values < 0.001). The urinary cadmium level of exposed group was 8.29 µg/g · cr, which was higher than that of the control group 2.03 µg/g · cr with significant difference (Z value was -11.39, P < 0.001). After stratified the total population by age, the urinary cadmium level in 40-49 years, 50-59 years and ≥ 60 years subgroups were 7.22, 8.71, and 13.10 µg/g · cr, which both were significantly higher than 1.80, 2.04, and 2.05 µg/g · cr in the control group (Z values were -5.22, -7.41, and -7.14, all P values < 0.001). After stratified the total population by gender, the urinary cadmium level of male and female were 5.12 and 12.36 µg/g · cr, which both were significantly higher than 1.79 and 2.16 µg/g · cr in the control group (Z values were -7.68 and -9.03, all P values < 0.001). Comparing the differences of renal dysfunction biomarkers (NAG, ß2-MG, RBP) between two groups. The level of urinary ß2-MG and RBP of exposed group were 0.21 and 0.04 µg/g · cr, which were higher than 0.05 and 0.00 µg/g · cr of the control group with significant difference (Z value was -7.08 and -9.65, all P values < 0.001). Pearson correlation analysis showed that NAG, ß2-MG and RBP were positively correlated with urinary cadmium and age, the correlation coefficients were 0.57, 0.49, 0.21 and 0.22, 0.26, 0.23 respectively (all P values < 0.001). After adjusting the effect of age, it was appeared that urinary cadmium levels contributed most to the alteration of NAG, ß2-MG and RBP, the standardized regression coefficients were 0.57, 0.49 and 0.20 (all P values < 0.001), and suggested that the cadmium body burden was one of the most important factors for renal dysfunction. CONCLUSION: Residents, who had cadmium contaminated rice and vegetables for a long time, would take the risk of increasing body burden of cadmium and urinary early biomarkers of renal tubular injury that referred to occurrence of renal dysfunction.

Identifying early urinary metabolic changes with long-term environmental exposure to cadmium by mass-spectrometry-based metabolomics.

Cadmium (Cd) is a common environmental pollutant, and urinary Cd (UCd) is generally used as a marker of exposure; however, our understanding on the related urinary metabolic changes caused by Cd exposure is still not clear. In this study, we applied a mass-spectrometry-based metabolomic approach to assess the urinary metabolic changes in human with long-term environmental Cd exposure, aimed to identify early biomarkers to assess Cd nephrotoxicity. Urine samples from 94 female never smokers aged 44-70 with UCd in the range of 0.20-68.67 µg/L were analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS) and gas chromatography-mass spectrometry (GC-MS). It was found that metabolites related to amino acid metabolism (L-glutamine, L-cystine, L-tyrosine, N-methyl-L-histidine, L-histidinol, taurine, phenylacetylglutamine, hippurate, and pyroglutamic acid), galactose metabolism (D-galactose and myo-inositol), purine metabolism (xanthine, urea, and deoxyadenosine monophosphate), creatine pathway (creatine and creatinine), and steroid hormone biosynthesis (17-α-hydroxyprogesterone, tetrahydrocortisone, estrone, and corticosterone) were significantly higher among those with a UCd level higher than 5 µg/L. Moreover, we noticed that the level of N-methyl-L-histidine had already started to elevate among individuals with a UCd concentration of ≥2 µg/L. The overall findings illustrate that metabolomics offer a useful approach for revealing metabolic changes as a result of Cd exposure.