Ambient nitrogen dioxide and composition-specific risk of urolithiasis: a multicenter time-stratified case-crossover study

Abstract

Background: Emerging evidence suggests that ambient air pollution and meteorological variation may trigger urolithiasis, but stone-composition–specific and lagged associations are poorly characterized.Methods: We conducted a multicenter, time-stratified case-crossover study in Guangzhou (training set) with 25,374 laboratory-confirmed urinary stones and two independent validation cohorts from Tianjin (n=99,552) and Guizhou (n=3,021). Six criteria pollutants (PM2.5, PM10, NO2, SO2, CO, O3_8h) and meteorological factors (temperature, precipitation, wind speed) were linked to case and referent days. Conditional logistic regression and generalized additive models quantified short-term (lag 0–7, moving averages) and long-term (6-month and 1-year) effects overall and for seven stone compositions, with stratified analyses by age, calendar period, season, and co-pollutant strata.Results: In Guangzhou, NO2 was consistently and positively associated with urolithiasis risk across single-pollutant, multi-pollutant, and GAM models. Short-term NO2 exposure showed the strongest effects at lag 0 and lag 2–4, particularly for carbonate apatite and calcium oxalate stones, and 1-year averages of NO2 were positively associated with uric acid stones. Higher temperature was generally protective, whereas PM10 displayed mainly inverse or U-shaped associations with overall and composition-specific risk. The NO2–urolithiasis association was robustly replicated in Tianjin and Guizhou, and key composition-specific patterns (NO2–calcium oxalate, PM10–carbonate apatite) were confirmed in the Guizhou cohort. Stratified analyses indicated greater susceptibility among young adults (18–65 years), in autumn, on both weekdays and weekends, and under specific co-pollutant and meteorological conditions, while results were stable across pre- and post-2019 periods.Conclusions: Ambient NO2 is a consistent and composition-dependent risk factor for urolithiasis, whereas PM10 and meteorological factors show more complex, often non-linear relationships. Integrating air quality management and heat-health strategies into kidney stone prevention may be particularly important in highly polluted, climatically vulnerable regions.