ObjectiveTo investigate the association between kidney function indicators in routine health examinations and the incidence of urinary stone disease using longitudinal repeated-measurement data. MethodsThis study was based on the large-scale longitudinal data in the WHALE study. Cox proportional hazards models were first applied to examine the associations between baseline kidney function indicators and incident urolithiasis. Subsequently, Poisson regression and mixed-effects models were used to analyze repeated-measurement data to further explore the relationships between kidney function indicators and urolithiasis. Latent class trajectory modeling was then employed to characterize longitudinal patterns of kidney function indicators. Based on the optimal trajectory models, logistic regression analyses and Cox regression analyses were performed to assess the associations between trajectory classes and the risk of urolithiasis. ResultsAmong 313 280 health examination participants included in the study, 8 864 incident cases of urolithiasis were identified during follow-up. In the baseline Cox analyses, cystatin C showed the strongest association with urolithiasis (HR=1.230, 95%CI 1.083 to 1.396, FDR=0.001). In analyses incorporating repeated measurements, serum uric acid demonstrated a strong association in both Poisson regression and mixed-effects models (RR=1.123, 95%CI 1.094 to 1.152, FDR<0.001; RR=1.106, 95%CI 1.075 to 1.137, FDR<0.001). In trajectory analyses, U-shaped trajectories of blood urea (HR=0.548, 95%CI 0.438 to 0.685, FDR<0.001) and uric acid (HR=0.910, 95%CI 0.857 to 0.685, FDR=0.005) were associated with a lower risk of urolithiasis. ConclusionBoth baseline levels and longitudinal changes in kidney function indicators measured during routine health examinations are significantly associated with the incidence of urolithiasis. Regular assessment and longitudinal monitoring of kidney function may contribute to the prevention and early identification of urolithiasis development and progression.