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

Area of Science:

• Environmental Health
• Epigenetics
• Nephrology

Background:

• Phthalate ester (PAE) exposure is increasingly linked to adverse health outcomes, including epigenetic aging and kidney dysfunction.
• Limited epidemiological data exists on the interplay between PAE exposure, epigenetic age acceleration (EAA), and renal function.
• Understanding these relationships is crucial for public health interventions targeting environmental exposures and aging-related diseases.

Purpose of the Study:

• To investigate if EAA mediates the association between PAE exposure and kidney function.
• To examine potential interaction effects between PAE exposure and EAA on kidney function.
• To provide epidemiological evidence on the combined impact of environmental toxins and biological aging on renal health.

Main Methods:

• Cross-sectional study of 818 community-dwelling individuals from the Taiwan Biobank cohort.
• Quantification of 11 urinary PAE metabolites and assessment of EAA using four biomarkers (AgeAccelResidual, AgeAccelHannum, AgeAccelPheno, AgeAccelGrim).
• Evaluation of kidney function via blood urea nitrogen and albumin-to-creatinine ratio (ACR), analyzed using generalized linear and mediation models.

Main Results:

• A significant negative association was found between a specific PAE metabolite (mono-(2-carboxymethylhexyl) phthalate) and AgeAccelGrim.
• AgeAccelGrim showed a significant positive association with albumin-to-creatinine ratio (ACR), indicating impaired kidney function.
• Significant interactions were identified between di(2-ethylhexyl) phthalate metabolites, AgeAccelGrim, and ACR, suggesting combined effects on renal dysfunction.

Conclusions:

• PAE exposure and EAA are independently associated with an increased risk of renal dysfunction.
• EAA may play a mediating role in the relationship between PAE exposure and kidney function impairment.
• The combined presence of PAE exposure and EAA may exacerbate the risk of early kidney function decline, highlighting the need for managing environmental exposures.