Serum HDL partially mediates the association between exposure to volatile organic compounds and kidney stones: A nationally representative cross-sectional study from NHANES

Environmental exposure to volatile organic compounds (VOCs) is ubiquitous, and this study explored whether exposure to VOCs is associated with the risk of kidney stones. We performed a nationally representative US cross-sectional study using data from five survey cycles (2011-2020) of the National Health and Nutrition Examination Survey (NHANES) program. Exposure to VOCs was determined by urine creatinine-corrected metabolites of VOCs (mVOCs). In total 5505 participants and 15 urine mVOCs were included for analysis, and the prevalence of kidney stones was 9.57 % (527/5505). Multivariable logistic regression showed that urine AMCC (parent VOCs (pVOCs): N, N-Dimethylformamide), 3,4-MHA (pVOCs: xylene), MA (pVOCs: ethylbenzene; styrene), DHBMA (pVOCs: 1,3-butadiene), HMPMA (pVOCs: crotonaldehyde) and 2HPMA (pVOCs: propylene oxide) were significantly associated with an increased risk of kidney stones in US general population. Sub-analysis revealed that there was a more pronounced association in women and the overweight/obesity group (body mass index ≥ 25). Moreover, the weighted quantile sum (WQS) regression model and the Bayesian kernel machine regression (BKMR) model consistently identified a positive association between co-exposure to VOCs and the risk of kidney stones, in which AMCC played the most important role among the 15 mVOCs. Mediation analysis further identified serum high-density lipoprotein cholesterol (HDL) as a mediator of the association between VOC co-exposure and kidney stones. Our study draws attention to the previously unknown positive associations between non-occupational VOC exposure and the risk of kidney stones in the general population. However, further studies are required to clarify the existence of such causation.