Association between Enzyme-Linked Immunosorbent Assay-Measured Kidney Injury Markers and Urinary Cadmium Levels in Chronic Kidney Disease

Cadmium exposure is associated with chronic kidney disease (CKD), but the optimal biomarker for early cadmium-associated nephrotoxicity in low-level exposure has not yet been established. We conducted a cross-sectional investigation involving 167 CKD patients stratified according to tertiles of urinary cadmium levels (UCd), in which enzyme-linked immunosorbent assay (ELISA)-measured novel renal biomarkers were utilized to assess the extent of renal injury associated with cadmium burden. In the analyses, urinary kidney injury molecule-1 (KIM-1) levels and age were the independent factors positively correlated with UCd after adjusting for covariates in non-dialysis-dependent CKD patients (high vs. low UCd, odds ratio (95% confidence interval), 1.0016 (1.0001–1.0032), p = 0.043, and 1.0534 (1.0091–1.0997), p = 0.018). Other conventional and novel renal biomarkers, such as serum creatinine, estimated glomerular filtration rate, CKD staging, urinary protein/creatinine ratio, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), and urinary epidermal growth factor (EGF) were not independently correlated with UCd in the analyses. In conclusion, our study found that the ELISA-measured urinary KIM-1 level could serve as an early renal injury marker in low-level cadmium exposure for non-dialysis-dependent CKD patients. In addition, age was an independent factor positively associated with UCd in this population.

Association Between Cadmium Exposure and Liver Function in Adults in the United States: A Cross-sectional Study

Objectives: Cadmium is widely used, leading to extensive environmental and occupational exposure. Unlike other organs, for which the harmful and carcinogenic effects of cadmium have been established, the hepatotoxicity of cadmium remains unclear. Some studies detected correlations between cadmium exposure and hepatotoxicity, but others concluded that they were not associated. Thus, we investigated the relationship between cadmium and liver damage in the general population.Methods: In total, 11 838 adult participants from National Health and Nutrition Examination Survey 1999-2015 were included. Urinary cadmium levels and the following liver function parameters were measured: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total bilirubin (TB), and alkaline phosphatase (ALP). Linear and logistic regression analyses were performed to assess the associations between urinary cadmium concentrations and each liver function parameter after adjusting for age, sex, race/ethnicity, annual family income, smoking status, alcohol consumption status, physical activity, and body mass index.Results: The covariate-adjusted results of the linear regression analyses showed significant positive relationships between log-transformed urinary cadmium levels and each log-transformed liver function parameter, where beta±standard error of ALT, AST, GGT, TB, and ALP were 0.049±0.008 (p<0.001), 0.030±0.006 (p<0.001), 0.093±0.011 (p<0.001), 0.034±0.009 (p<0.001), and 0.040±0.005 (p<0.001), respectively. Logistic regression also revealed statistically significant results. The odds ratios (95% confidence intervals) of elevated ALT, AST, GGT, TB, and ALP per unit increase in log-transformed urinary cadmium concentration were 1.360 (1.210 to 1.528), 1.307 (1.149 to 1.486), 1.520 (1.357 to 1.704), 1.201 (1.003 to 1.438), and 1.568 (1.277 to 1.926), respectively.Conclusions: Chronic exposure to cadmium showed positive associations with liver damage.

Exposure to airborne cadmium and breast cancer stage, grade and histology at diagnosis: findings from the E3N cohort study

Molecular studies suggest that cadmium due to its estrogenic properties, might play a role in breast cancer (BC) progression. However epidemiological evidence is limited. This study explored the association between long-term exposure to airborne cadmium and risk of BC by stage, grade of differentiation, and histological types at diagnosis. A nested case–control study of 4401 cases and 4401 matched controls was conducted within the French E3N cohort. A Geographic Information System (GIS)-based metric demonstrated to reliably characterize long-term environmental exposures was employed to evaluate airborne exposure to cadmium. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. There was no relationship between cadmium exposure and stage of BC. Also, no association between cadmium exposure and grade of differentiation of BC was observed. However, further analyses by histological type suggested a positive association between cadmium and risk of invasive tubular carcinoma (ITC) BC [ORQ5 vs Q1 = 3.4 (95% CI 1.1–10.7)]. The restricted cubic spline assessment suggested a dose–response relationship between cadmium and ITC BC subtype. Our results do not support the hypothesis that airborne cadmium exposure may play a role in advanced BC risk, but suggest that cadmium may be associated with an increased risk of ITC.