Associations of exposure to heavy metal mixtures with kidney stone among US adults: A cross-sectional study

Assessing the effects of heavy metals (HMs) on kidney stone is often limited to analyzing individual metal exposures, with studies on the effects of exposure to mixtures of HMs being scarce. To comprehensively evaluate the relationship between exposure to mixed HMs and kidney stones, we analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2007-2016, which included 7809 adults. We used multiple statistical methods, including multiple logistic regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp) and bayesian kernel machine regression (BKMR), to assess the association between single HM and mixed exposure to HMs and kidney stones. Firstly, in single exposure analysis, urinary cadmium (Cd) and cobalt (Co) demonstrated a positive association with the risk of kidney stones. Secondly, various other approaches consistently revealed that mixed exposure to HMs exhibited a positive association with kidney stone risk, primarily driven by Cd, Co, and barium (Ba) in urine, with these associations being particularly notable among the elderly population. Finally, both BKMR and survey-weighted generalized linear models consistently demonstrated a significant synergistic effect between urinary Co and urinary uranium (Ur) in elevating the risk of kidney stones. Overall, this study provides new epidemiological evidence that mixed exposure to HMs is associated with an increased risk of kidney stones. Further prospectively designed studies are needed to confirm these findings.