Sweetened beverage intake and risk of incident kidney stone: results from the UK Biobank

Background: To investigate the associations between consumption of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and natural juices (NJs) and incident kidney stone disease (KSD), and to assess whether genetic susceptibility modifies these associations. Methods: We conducted a prospective cohort study of 191,863 UK Biobank participants free of KSD at baseline. Beverage consumption was assessed using web-based 24-h dietary recalls (2009-2012), categorized as 0, 0.1-1.0, 1.1-2.0, and >2.0 units/day (1 unit = 250 ml). A polygenic risk score (PRS) comprising 22 single nucleotide polymorphisms quantified genetic susceptibility. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), with gene-environment interactions evaluated through stratified analyses. Results: for trend = 0.419). Higher PRS independently predicted KSD risk but did not significantly modify beverage-KSD associations (all P for interaction >0.05). Joint analyses revealed highest KSD hazard among participants with high SSB intake and low PRS (HR 2.09, 95% CI 1.46-2.98). Conclusion: Higher SSB consumption is dose-dependently associated with increased KSD risk, while ASBs show non-linear associations and NJs demonstrate no significant association. Genetic susceptibility independently predicts KSD risk but does not substantially modify beverage-KSD relationships. Limiting SSB intake represents an important modifiable strategy for KSD prevention independent of genetic predisposition.