Association Between Metabolic Score for Insulin Resistance Trajectories and the Risk of Kidney Stone Disease: A Retrospective Cohort Study

Background: The Metabolic Score for Insulin Resistance (METS-IR) is a reliable surrogate marker for insulin resistance, which is known to be associated with kidney stone disease (KSD). However, the impact of longitudinal METS-IR trajectories on KSD risk remains unclear. This study aimed to investigate the association between METS-IR trajectories over time and the risk of incident KSD.

Methods: This retrospective cohort study enrolled adult participants who underwent routine annual health check-ups. Longitudinal METS-IR trajectories were identified using trajectory modeling. The primary outcome was new-onset KSD. Cumulative incidence curves and Cox proportional hazards regression models were utilized to evaluate the association between different METS-IR trajectories and KSD incidence. Additionally, the C-index and Net Reclassification Improvement (NRI) were used to assess the incremental predictive value of the models. Subgroup analyses were performed to test the robustness of the findings across various baseline clinical characteristics.

Results: A total of 39,305 eligible participants (mean age 42.0 years; 54.2% male) were included. Three distinct METS-IR trajectories were identified: low-stable (n = 15,033, 38.2%), moderate-stable (n = 17,631, 44.9%), and high-stable (n = 6,641, 16.9%). Participants in the high-stable group exhibited worse metabolic profiles at baseline. During a median follow-up of 3.9 years (interquartile range, 2.6–4.9 years), 2,125 participants (5.4%) developed KSD. Cumulative incidence curves demonstrated a significantly higher KSD risk in the high-stable group (Log-rank P < 0.001). In the fully adjusted model, the high-stable trajectory was independently associated with a significantly increased risk of KSD compared to the low-stable group, with an adjusted hazard ratio (HR) of 1.362 (95% confidence interval [CI]: 1.169–1.588, P < 0.001). The risk for the moderate-stable group was attenuated and not statistically significant (adjusted HR: 1.117, 95% CI: 0.986–1.265, P = 0.081). Stratified analyses revealed no significant interactions across age, sex, hypertension, or diabetes subgroups (all P for interaction > 0.05). While the trajectory model showed comparable predictive accuracy to the baseline METS-IR model, METS-IR provided a significant incremental risk reclassification benefit over body mass index (BMI) alone (NRI = 0.107, 95% CI: 0.011–0.196).

Conclusions: Maintaining a consistently high METS-IR level over time is an independent risk factor for new-onset KSD. Although longitudinal trajectories primarily reflect baseline metabolic status without yielding significant incremental predictive value, baseline METS-IR assessment significantly enhances KSD risk stratification beyond obesity itself.