Comprehensive analysis of the association between volatile organic compound pollutants and chronic kidney disease in hypertensive populations: insights from multi-omics approaches and identification of potential therapeutic targets

Environmental pollutants, including volatile organic compounds (VOCs), are increasingly linked to chronic kidney disease (CKD), yet this association in hypertensive populations is not well understood. This study used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 to explore the association between VOC exposure and CKD in 1,159 hypertensive adults (representing 33.6 million people). Sixteen urinary metabolites of VOC exposure (mVOCs) were analyzed with multiple statistical methods like logistic regression and weighted quantile sum (WQS) regression, alongside machine learning approaches. Results showed that higher levels of certain mVOCs were linked to increased CKD risk, with logistic regression indicating a significant association (e.g., odds ratio [OR] for the mVOC HMPMA (Q4) = 3.52, 95% CI = 1.66-7.45, P = 0.001). WQS models confirmed this association in males (OR = 1.77, 95% CI: 1.05-2.99; P = 0.033) and highlighted HMPMA (from the VOC crotonaldehyde) and PGA (from the VOC ethylbenzene) as key contributors with other models. Further analysis using network toxicology, a method to study chemical-biological interactions, identified related targets such as CCL22 and Casp3, with molecular docking confirming that HMPMA and PGA interact with these proteins. This study reveals a significant link between VOC exposure and CKD risk in hypertensive individuals, though only 2 mVOCs (HMPMA and PGA) were analyzed in downstream toxicological studies at the molecular level, suggesting a need for broader research to confirm causality.