Diabetes Minimally Mediated the Association Between PM_2.5 Air Pollution and Kidney Outcomes

Epidemiologic observations suggest that exposure to ambient fine particulate matter (PM_2.5) is associated with increased risk of chronic kidney disease (CKD) and diabetes, a causal driver of CKD. We evaluated whether diabetes mediates the association between PM_2.5 and CKD. A cohort of 2,444,157 United States veterans were followed over a median 8.5 years. Environmental Protection Agency data provided PM_2.5 exposure levels_. Regression models assessed associations and their proportion mediated. A 10 µg/m³ increase in PM_2.5 was associated with increased odds of having a diabetes diagnosis (odds ratio: 1.18, 95% CI: 1.06-1.32), use of diabetes medication (1.22, 1.07-1.39), and increased risk of incident eGFR <60 ml/min/1.73 m² (hazard ratio:1.20, 95% CI: 1.13-1.29), incident CKD (1.28, 1.18-1.39), ≥30% decline in eGFR (1.23, 1.15-1.33), and end-stage renal disease (ESRD) or ≥50% decline in eGFR (1.17, 1.05-1.30). Diabetes mediated 4.7% (4.3-5.7%) of the association of PM_2.5 with incident eGFR <60 ml/min/1.73 m², 4.8% (4.2-5.8%) with incident CKD, 5.8% (5.0-7.0%) with ≥30% decline in eGFR, and 17.0% (13.1-20.4%) with ESRD or ≥50% decline in eGFR. Diabetes minimally mediated the association between PM_2.5 and kidney outcomes. The findings will help inform more accurate estimates of the burden of diabetes and burden of kidney disease attributable to PM_2.5 pollution.