The impact of exposure to metals on chronic kidney disease (CKD) has only been investigated in two-way or single metal interactions in previous studies. We investigated the associations between five single metals in blood and their mixed exposure and CKD by using the machine learning approach. Relevant data were extracted from the National Health and Nutrition Examination Survey (NHANES 2011-2020), and the level of five metals in blood detected by inductively coupled plasma mass spectrometry was considered as exposures, namely, cadmium (Cd), lead (Pb), total mercury (Hg), manganese (Mn), and selenium (Se). The correlations between individual metal and metal mixtures and CKD were then evaluated by survey-multivariable logistic regression (SMLR), generalized weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Altogether, our study included 12,412 participants representing 572.6 million non-institutionalized US adults. Several single metals with the high quartile of exposure showed a positive association with the CKD ratio including Cd [(AOR = 1.873, 95% CI: 1.537, 2.284), Q4], Pb [(AOR = 1.559, 95% CI: 1.295, 1.880), Q4], and total Hg [(AOR = 1.169, 95% CI: 1.018, 1.343), Q2], while Mn [(AOR = 0.796, 95% CI: 0.684, 0.927), Q2] and Se [(AOR = 0.805, 95% CI: 0.664, 0.976), Q4] were negatively associated with the CKD ratio. In light of the positive fit of the WQS regression model, a significantly positive correlation was found between mixed metals and CKD (AOR = 1.373, 95% CI: 1.224, 1.539) after full covariate adjustment, and a similar finding was also detected in the BKMR model. Our study revealed that each single metal including Cd, Pb, and total Hg might have a positive association with CKD while this association was negative for both Mn and Se. The five metals might have a positive joint effect on CKD.

Maternal exposure to metals may pose a risk to the health of newborns, however, the underlying mechanisms remain ambiguous. Herein, we aimed to investigate the influence of metals exposure on birth outcomes and reveal the importance of metabolites in the exposure-outcomes association by using metabolomics methods.
In our study, 292 mother-pairs were included who were recruited from the affiliated hospitals of Nanjing Medical University between 2006 and 2011. We measured fifteen metals (mercury, lead, vanadium, arsenic, zinc, cadmium, rubidium, copper, cobalt, iron, molybdenum, strontium, thallium, magnesium and calcium) and metabolites in maternal second trimester serums by using inductively coupled plasma mass spectrometry and ultra-high performance liquid chromatography high resolution accurate mass spectrometry, respectively. A multi-step statistical analysis strategy including exposome-wide association study (ExWAS) model, variable selection models and multiple-exposure models were performed to systematically appraise the associations of individual and mixed metals exposure with birth outcomes. Furthermore, differential metabolites that associated with metals exposure and birth outcomes were identified using linear regression models.
Metal\'s levels in maternal serums ranged from 0.05 μg/L to 1864.76 μg/L. In the ExWAS model, maternal exposure to arsenic was negatively associated with birth weight (β = 188.83; 95% CI: -368.27, -9.39), while maternal mercury exposure showed a positive association (β = 533.65; 95%CI: 179.40, 887.90) with birth weight. Moreover, each unit increase in mercury (1 ng/mL-log transformed) was associated with a 1.82 week-increase (95%CI: 0.85, 2.79) in gestational age. These findings were subsequently validated by variable selection models and multiple exposure models. Metabolomic analysis further revealed the significant role of 3-methyladenine in the relationship between arsenic exposure and birth weight.
This study provides new epidemiological evidence indicating the associations of metals exposure and neonatal birth outcomes, and emphasizes the potential role of metabolite biomarkers and their importance in monitoring adverse birth outcomes.

In order to document the exposure to trace metals among urban schoolchildren and rural working children, we measured the urinary concentrations of metals in schoolchildren from two areas of differing traffic intensity in Lahore, and in children working in carpet weaving or the brick industry outside Lahore. In a cross-sectional design, we recruited a convenience sample of 339 children aged 8-12 years (mean age 9.9 y, SD 1.4; 47% girls) from two elementary schools in Lahore - one situated in a high air pollution area (n=100) and one situated in an area with lower air pollution (n=79) - and from the carpet weaving industry (n=80) and brick industry (n=80). A spot urine sample was collected and concentrations of 20 metals and metalloids were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Samples of drinking water were similarly analyzed. In general, the urinary concentrations of several toxic metals (including Cr, Mn, As, Mo, Cd, Pb, U) were higher than international reference values. Concentrations of As were especially elevated in children working in the brick making industry [geometric mean (GM) 118 μg/L], but they were also high among urban schoolchildren (GM 68 μg/L and 56 μg/L). Lead (Pb) was higher in urine from schoolchildren in the high air pollution area (GM 11 μg/L) than in those from the lower pollution area (GM 5.3 μg/L). Uranium (U) was high in both carpet weavers (GM 0.28 μg/L) and brick kiln workers (GM 0.45 μg/L). Concentrations of As, Pb, and U in drinking water corresponded well with urinary concentrations of metals. This descriptive study provides evidence for a high exposure to several toxic metals in this area of Pakistan. The concentrations of urinary As are in the order of those found in other regions of the world with high environmental exposure to As. The sources and pathways of exposure and the health significance of these findings need to be further investigated.