Long-term impact of PM_2.5 exposure on diabetic kidney disease patients considering time-dependent medication...

Ambient air pollutants adversely affect renal function and increase type 2 diabetes incidence. However, the impact of air pollution on diabetic kidney disease (DKD) patients remains underexplored, with limited consideration of medication-related effects. We assessed the influence of air pollutants on DKD patients while meticulously adjusting for medication use.

We retrospectively enrolled DKD patients. Primary and secondary outcomes included end-stage kidney disease (ESKD) and a composite (ESKD and mortality). Nationwide forecasted ultra-high-resolution air pollutant data [2.5-μm particulate matter (PM_2.5), 10-μm particulate matter (PM₁₀), nitrogen dioxide (NO₂), carbon monoxide (CO)] were obtained from the Ai-Machine learning Statistics Collaborative Research Ensemble for Air pollution, Temperature, and all types of Environmental exposures (AiMS-CREATE). Monthly updated ambient air pollutants and medication prescription information were considered time-varying variables in multivariable time-dependent Cox analyses.

Patients (n = 9482) were followed for a median of 9 (ESKD) and 11 (composite outcome) years; 20.6% progressed to ESKD and 46.7% experienced composite outcomes. The DKD-stage patient distribution was 12.5% (stage 1-2), 35.8% (stage 3) and 51.6% (stage 4-5). Initial renin-angiotensin system blocker use increased from 37.4% to 58.5% during year 1 then gradually decreased. During follow-up, all four air pollutant concentrations significantly decreased, with CO exhibiting the most pronounced decline. The 1-month lagged PM_2.5 exposure (Lag1_PM_2.5) was significantly associated with higher ESKD progression risk {adjusted hazard ratio [aHR] 1.28 [95% confidence interval (CI) 1.085-1.508]}, whereas PM_2.5 itself showed no significance [aHR 1.05 (95% CI 0.872-1.260)]. Both exposures increased the composite outcome risk (PM_2.5 aHR 1.16 Lag1_PM_2.5 aHR 1.15). PM₁₀ and Lag1_PM₁₀ showed no significant associations with either ESKD progression or composite outcomes. NO₂ exposure increased ESKD progression risk but was not associated with composite outcomes.

Even after comprehensive medication use adjustment, higher PM_2.5 exposure was independently associated with an increased risk of ESKD progression and composite outcome in DKD patients.