A study on the association between polycyclic aromatic hydrocarbon (PAH) exposure and kidney function indicators in adolescents: an integrated research combining statistical mediation analysis and network toxicology
摘要
Polycyclic aromatic hydrocarbons (PAHs) are a class of environmental pollutants widely present in daily life. However, the association between mixed exposure to PAHs and kidney function remains unclear. This study aimed to analyze and evaluate the relationship between urinary PAH metabolite levels and multiple kidney function parameters in adolescents. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. The cross-sectional associations between urinary PAH metabolites and kidney parameters were examined using multiple linear regression models. In addition, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were applied to evaluate the effects of mixed exposure to PAH metabolites on kidney function indicators. Statistical mediation analysis suggested that alkaline phosphatase (ALP) may play a potential mediating role. Furthermore, hypothesis-generating bioinformatics analyses were conducted using network toxicology and molecular docking approaches. A total of 1428 adolescents were included in this study. The results showed that all PAH metabolites were negatively associated with serum creatinine (Scr) (PFDR < 0.05) and positively associated with estimated glomerular filtration rate (eGFR) (PFDR < 0.05). Both WQS and BKMR models consistently indicated that mixed exposure to PAHs was positively associated with eGFR and negatively associated with Scr, urinary creatinine (Ucr), and serum uric acid (SUA). Bioinformatics analysis further identified five potential target proteins: albumin (ALB), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), insulin-like growth factor 1 (IGF1), and peroxisome proliferator-activated receptor gamma (PPARG). Molecular docking was subsequently performed to predict the binding affinities between PAH metabolites and these candidate proteins. Our study identified an association between PAH exposure and kidney function in adolescents. These findings suggest that PAH exposure may be related to early alterations in kidney function among adolescents. However, the clinical significance and long-term health effects of these associations require further validation through longitudinal studies and mechanistic investigations. Nevertheless, our findings highlight concerns regarding the potential adverse effects of PAH metabolite exposure on adolescent kidney function and underscore its relevance for public health.