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 During 13.5 years mean follow-up, 2,024 incident KSD cases occurred. Compared with non-consumers, participants consuming >2 units/day of SSBs had 51% higher KSD risk (HR 1.51, 95% CI 1.17–1.95) with significant dose-response relationship ( P for trend < 0.001). ASBs showed elevated risk at 1.1–2.0 units/day (HR 1.25, 95% CI 1.02–1.28) without linear trend ( P = 0.192). NJs showed no significant association ( P 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.