Exposure to Cadmium, Lead, Mercury, and Arsenic and Uric Acid Levels: Results from NHANES 2007-2016.

Mechanisms underlying abnormal uric acid (UA) levels from exposure to toxic metals/metalloids have not been not fully elucidated, especially in the context of mixtures. The aim was to identify major toxic metals/metalloids that affected UA levels with a mixture exposure concept in the association model. From 2007-2016 National Health and Nutrition Examination Survey (NHANES), 4794 adults were involved. Serum UA (SUA) and SUA to serum creatinine ratio (SUA/SCr) were used to estimate the UA levels, and cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) in the blood and/or urine were evaluated in the study. We assessed the associations between toxic metals and UA levels using linear regression and Bayesian kernel machine regression (BKMR). The median [P, P] SUA/SCr and SUA level were 6.22 [5.27, 7.32] and 0.83 [0.72, 0.98], respectively. There was no difference for SUA/SCr by gender (men, 6.25 [5.39, 7.29]; women, 6.17 [5.17, 7.36], P = 0.162), but men had higher SUA than women (men, 0.95 [0.85, 1.05]; women, 0.72 [0.64, 0.82], P < 0.001). Blood Pb (β = 0.651 and β = 1.014) and urinary Cd (β = 0.252 and β = 0.613) were positively associated with SUA/SCr, and urinary Pb (β =  - 0.462 and β =  - 0.838) was inversely associated with SUA/SCr in multivariate linear regression analysis. However, urinary As (β = 0.351) was positively associated with SUA/SCr only in men. BKMR showed that higher concentrations of exposure to a mixture of toxic metals were positively associated with higher UA levels, where Cd, Pb, and urinary As contributed most to the overall mixture effect in men, while Pb and urinary Cd in women. Our study provided the first evidence that mixtures of metals are associated with the UA levels. Increased concentrations of metals, mainly blood Pb, urinary Cd, and As (only in men) may increase the level of UA.