Causal relationship between basal metabolic rate and kidney stone disease: from discovery in US NHANES to evidence in UK Biobank cohorts

Background: Our previous genome-wide association study (GWAS) suggested a potential negative causal relationship between basal metabolic rate (BMR) and kidney stone disease (KSD) from a genetic standpoint. This study aimed to further investigate their association from a clinical etiological perspective across diverse global populations and to elucidate their dose-response relationship. Methods: A total of 21 140 adults from the US NHANES (2007–2020) and 289 007 participants without a prior history of KSD from the UK Biobank (2006–2024) were analyzed using cross-sectional and prospective cohort study designs, respectively. Data were collected through questionnaires and physical examinations. Multivariable logistic regression models and restricted cubic spline (RCS) analyses were employed to assess the relationship between BMR and the risk of KSD, adjusting for potential confounders. Subgroup and sensitivity analyses were conducted to explore gender- and age-related differences and evaluate the robustness of the results. Results: In the NHANES cohort, the fully adjusted odds ratio (OR) for the highest BMR quartile (Q4) compared to the lowest quartile (Q1) was 0.49 (95% CI: 0.35, 0.70; P for trend < 0.001). During the follow-up period in the UK Biobank cohort, 3620 participants ultimately developed KSD, and the relevant analysis further confirmed this negative causal association, with an OR of 0.72 (95% CI: 0.59, 0.89; P for trend = 0.003). In both cohorts, higher BMR was associated with a decreased risk of KSD, with consistent trends observed across sex and age subgroups. Sensitivity analyses validated the robustness of these findings. Conclusions: In conclusion, a higher BMR appears to be a protective factor against KSD, with a negative causal association identified. Lifestyle interventions aimed at increasing BMR may help prevent the development of kidney stones.