BACKGROUND: Whether ultra-processed food (UPF) consumption is associated with the risk of kidney stone is not explored. Furthermore, it remains unclear if kidney stone-related genetic predisposition could affect this association. Therefore, we aim to examine the associations of UPF consumption, genetic predisposition, and their interactions with the risk of kidney stone. METHODS: In this study, 166,427 middle-aged participants from the UK Biobank were enrolled. UPF intake was assessed according to the NOVA food classification system and based on 24-h dietary recalls. A polygenic-risk score (PRS) of 20 single-nucleotide polymorphisms was calculated for kidney stone. Cox proportional hazards regression model was used to investigate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of incident kidney stone. RESULTS: After 1,510,300 person-years of follow-up, 1369 participants developed kidney stone. UPF consumption was positively associated with the risk of kidney stone (P for trend <
0.01). Compared with participants in the first tertile of UPF intake, those in the third tertile had a 24% (HR: 1.24
95% CI 1.07-1.43) increased risk of kidney stone. Compared to total UPF intake, the consumption of UPF excluding yogurt and cereals was associated with a greater risk of kidney stones (HR: 1.32
95% CI 1.15-1.51). Even though no significant interaction effect between UPF and PRS was found (P for interaction = 0.09), this association was only observed in participants with low and middle PRS, but not in those with high PRS. In the joint association analysis, compared to participants with low UPF consumption and PRS, those with high UPF consumption and PRS experienced the highest risk of kidney stone (HR: 1.95, 95% CI 1.51, 2.51). This association was consistently observed in participants regardless of sex, age, and BMI. DISCUSSION: The results demonstrated that higher consumption of UPF is associated with an increased risk of kidney stone. These insights could prove valuable for informing public health policies aimed at preventing kidney stone. Further intervention studies are needed to confirm and elaborate on our results.