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

Emerging evidence suggests that ambient air pollution and meteorological variation may trigger urolithiasis, but stone-composition-specific and lagged associations are poorly characterized.

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.

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.

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.