PM_2.5 and constituents exacerbate decline of kidney function: The modification of glucose metabolism

Ambient PM_2.5 is a recognized risk factor for kidney disease, yet the contributions of its specific constituents and underlying mechanisms across different glycemic statuses remain poorly understood. This longitudinal study analyzed 16,645 adults in Wuhan, China (2017 - 2024) to evaluate the individual and joint effects of PM_2.5 and its five major constituents (sulfate, nitrate, ammonium, organic matter, and black carbon) on estimated glomerular filtration rate (eGFR) decline in normal, prediabetes, and diabetes populations. Exposure was assessed using the high-resolution Tracking Air Pollution in China dataset. Linear mixed-effects models showed that each 1 μg/m³ increase in PM_2.5 was associated with a 0.32% decline in eGFR (95% CI: 0.25 - 0.39). All five constituents were significantly associated with accelerated eGFR decline. Mixture analyses using weighted quantile sum and quantile g-computation revealed black carbon as the dominant contributor in normal (50.5%, WQS) and diabetes (58.7%, Qg-comp) individuals, whereas ammonium contributed most in prediabetes (76.9%, Qg-comp). Mediation analysis indicated that the Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index mediated 2% of the association in normal adults and the Cholesterol Index (CHO) mediated 2% in prediabetes, with no significant mediation in diabetes participants. Using the parametric g-formula, reducing PM_2.5 to 9 μg/m³ was estimated to reduce the risk of kidney function decline by 11.22%. These findings highlight heterogeneity in PM_2.5-related kidney injury across glycemic statuses and demonstrate that stringent air quality regulations could substantially mitigate kidney disease burden, particularly in metabolically vulnerable populations.