Impact of air pollution exposure on chronic kidney disease and type 2 diabetes: A FIDELITY analysis

Exposure to particulate matter air pollution ≤2.5 µm (PM_2.5) is associated with cardiovascular (CV) and kidney morbidity and mortality. This post hoc analysis of FIDELITY, a prespecified pooled analysis of phase 3 randomized clinical trials (FIDELIO-DKD [NCT02540993], FIGARO-DKD [NCT02545049]), determined the impact of PM_2.5 exposure on CV and kidney events and the effects of finerenone on these outcomes across PM_2.5 exposures in patients with CKD and T2D.

Patients with CKD and T2D on optimized renin-angiotensin system blockade were randomized 1:1 to finerenone or placebo. Key outcomes included composite CV outcomes (CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure); composite kidney outcomes (kidney failure, sustained ≥57 % decrease in eGFR, kidney-related death); combined composite CV and kidney outcomes; and safety. Outcomes were stratified by PM_2.5 exposure and patients grouped into quartiles of median PM_2.5 exposure with interquartile range as cutoffs.

Median PM_2.5 exposure was 15.5 µg/m³ (N = 12 990). Increased PM_2.5 exposure was associated with higher occurrence of CV and kidney events. Finerenone reduced composite CV (hazard ratio [HR], 0.86; 95 % CI, 0.78-0.95), kidney (HR, 0.76; 95 % CI, 0.66-0.88) and combined CV and kidney (HR, 0.83; 95 % CI, 0.76-0.90) outcomes versus placebo across PM_2.5 exposures (P _interaction=0.37, 0.14, and 0.74, respectively). Proportions of adverse events (AEs) and serious AEs were generally balanced between treatment arms. Across PM_2.5 quartiles, hyperkalemia was more frequent with finerenone, but few led to hospitalization.

Increased PM_2.5 exposure is associated with higher occurrence of CV and kidney events. Finerenone lowered the risk of CV and kidney events regardless of PM_2.5 exposure levels in patients with CKD and T2D.