Incident chronic kidney disease in relation to later-life exposure to PM2.5 constituents and extreme temperature events in a national cohort study.

BACKGROUND: Accumulating evidence has linked ambient fine particulate matter (PM2.5) and suboptimal temperatures to renal metabolic function in populations. However, it remains unstudied regarding the individual and interactive associations of PM2.5 components and extreme temperature events (ETEs) with the incidence of chronic kidney disease (CKD).

METHODS: A nationwide CKD-free cohort of 6438 participants aged 45 years and above were enrolled from 125 cities across China's mainland and followed up from 2011 to 2015. Daily estimates of major PM2.5 constituents (black carbon [BC], organic matter [OM], nitrate [NO3-], sulfate [SO42-], and ammonium [NH4+]) and ambient temperatures were assessed using well-validated spatial-temporal models at 0.1° × 0.1° resolution. ETEs were defined using multiple temperature thresholds (2.5-10th percentiles for cold spells, 90-97.5th percentiles for heat waves) and durations (2-4 days). Cox proportional hazards regression models were utilized to evaluate the hazard ratio (HR) of CKD incidence and its 95% confidence interval (CI) associated with long-term exposure to cold spells, heat waves, and PM2.5 constituents. Stratified analyses were conducted to compare PM2.5-related risks between low- and high-frequency groups of ETEs exposure, and ETEs-related risks between low- and high-level groups of PM2.5 exposure. Interactive effects of PM2.5 and ETEs exposures were assessed using interaction terms and the metric of relative excess risk due to interaction (RERI).

RESULTS: In the overall population, a 10-μg/m3 increase in PM2.5 mass was associated with an increased risk of CKD incidence (HR=1.104, 95% CI: 1.016-1.201). Among PM2.5 constituents (per 1-μg/m3 increase), NH4+ showed the strongest association (1.149, 95% CI: 1.082-1.221), followed by SO42- (1.145, 95% CI: 1.086-1.206) and NO3- (1.090, 95% CI: 1.056-1.126). Overall, ETEs defined by various thresholds and durations were significantly associated with elevated CKD risks, with HR estimates (per 10-day rise) ranging from 1.047 (95% CI: 1.015-1.080) to 1.330 (95% CI: 1.251-1.415) for cold spells and from 1.038 (95% CI: 1.012-1.065) to 1.144 (95% CI: 1.085-1.207) for heat waves. Stratified analyses showed intensified PM2.5-related CKD risks under high-ETE exposure compared to low-ETE exposure, and higher ETEs-related risks in high-PM2.5 groups than low-PM2.5 groups. We observed generally consistent evidence for the synergistic interaction effects of cold spells and PM2.5 constituents in triggering CKD events (HR >1 for interaction and RERI >0), under multiple definitions of cold spells.

CONCLUSIONS: Later-life (individuals aged ≥45 years) exposures to PM2.5 constituents and ETEs were individually and interactively associated with an increased risk of incident CKD events in middle-aged and older adults. Our findings highlighted the public health urgency of collective response to climate change crisis and ambient PM2.5 pollution.