Supplementary Material for: The impact of air pollution on kidney function: A two-sample Mendelian randomization study

Background: Chronic kidney disease (CKD) is a growing public health problem, resulting in significant morbidity and mortality. The relationship between air pollution (particulate matter (PM)2.5, PM2.5-10, and PM10, Nitrogen oxides (NOX), Nitrogen dioxide (NO2)) and kidney function has raised concerns. However, the causal relation remains uncertain. This study aimed to determine the impact of air pollution exposure on kidney function. Methods: A two-sample Mendelian randomization (MR) study was launched using summary data from genome-wide association studies. Five MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode, were applied to investigate the potential causal relationship between air pollution exposure and kidney function, with the IVW method serving as the primary approach. MR-Egger regression, MR-PRESSO, and leave-one out analysis were used to strengthen the results. Results: The MR analysis revealed a significant association between exposure to PM2.5-10 and an increased risk in CKD (OR:1.631; 95% confidence interval [CI] 1.161, 2.290), eGFRcrea (β: -0.013; 95% CI -0.021, -0.004), and eGFRcys (β: -0.024; 95% CI -0.039, -0.008). NOx was identified as a risk factor for eGFRcys (β: -0.016; 95% CI -0.029, -0.003). NO2 was associated with increased urine albumin-to-creatinine ratio (UACR) levels (β: 0.039; 95% CI 0.009, 0.069). However, no significant relationship was observed between PM2.5 or PM10 exposure and kidney function. No significant heterogeneity or horizontal pleiotropy was observed. Conclusion: Our MR analysis reveals a genetic causal relation between air pollution especially PM2.5-10 and deteriorating kidney function, which may help provide new insights into further mechanisms and clinical studies in air pollution-mediated kidney diseases.