Accelerated aging as a mediator of the association between co-exposure to multiple air pollutants and risk of chronic kidney disease

Background: The association between co-exposure to multiple air pollutants and the occurrence of chronic kidney disease (CKD) was not well-established, and the mediating role of accelerated aging in this association remained uncertain.

Methods: Using a cohort of 313,908 participants without CKD at baseline from the UK Biobank, we examined the potential association between co-exposure to multiple air pollutants, including PM_2.5, PM₁₀, PM_2.5-10, NO₂ and NO_x, and the incidence of CKD by calculating an air pollution score. Mediation analyses were performed to examine the mediating role of accelerated aging (PhenoAgeAccel or KDM-BioAgeAccel) in this association.

Results: During the median follow-up time of 12.9 years, 11,117 participants developed CKD. The results showed that per interquartile range (IQR) increment in air pollution score led to an approximately 9.0 % (6.6-11.4 %) elevated risk of occurring CKD. Compared to the first quartile (Q1) of air pollution score, those in the highest quartile (Q4) had a 21.2 % (14.8-27.9 %) higher risk of developing CKD (P_trend<0.001). Mediation analyses suggested that PhenoAgeAccel and KDM-BioAgeAccel significantly mediated 1.5 % and 5.7 % of the association between air pollution score and incident CKD, respectively.

Conclusion: Co-exposure to multiple air pollutants could increase the risk of developing CKD, with accelerated aging serving as a partial mechanism in the relationship between air pollution and CKD. These findings highlight the importance of reducing air pollution, and suggest a possible mechanism from air pollution to CKD through accelerated aging.