Does epigenetic aging mediate the associations between phthalate exposure and renal function?

Emerging evidence suggests that phthalate ester (PAE) exposure accelerates epigenetic aging and impairs kidney function. However, very few epidemiological studies have explored the associations between PAE exposure, epigenetic age acceleration (EAA), and kidney function. The present cross-sectional study investigated whether EAA mediates the effect of PAE exposure on kidney function and assessed the potential interaction effects of PAE exposure and EAA on kidney function. The data of 818 community-dwelling individuals were collected from the Taiwan Biobank cohort. Eleven urinary PAE metabolites were quantified. EAA was assessed using four biomarkers: AgeAccelResidual, AgeAccelHannum, AgeAccelPheno, and AgeAccelGrim. Kidney function was evaluated on the basis of blood urea nitrogen level and the albumin-to-creatinine ratio (ACR). Generalized linear models were used to identify the associations and interactions among the study variables. A mediation analysis was performed to determine whether EAA mediates the effect of PAE exposure on kidney function. Generalized linear models revealed a significant negative association between mono-(2-carboxymethylhexyl) phthalate and AgeAccelGrim (β = -0.199; 95 % confidence interval = -0.339 to -0.060). Moreover, AgeAccelGrim was positively associated with ACR (β = 0.037; 95 % confidence interval = 0.019-0.056). Furthermore, significant interactions were observed among di(2-ethylhexyl) phthalate metabolites, AgeAccelGrim, and ACR. Together, the findings indicate that PAE exposure and EAA are independently associated with an increased risk of renal dysfunction. The coexistence of the two factors may further increase the risk of early kidney function impairment.