Blood Calcium, Genetic Risk, and Risk of Incident Kidney Stone: A Population-Based Cohort Study

Objective To investigate the association between blood calcium concentration and incident kidney stone as well as to assess the role played by genetic susceptibility. Methods We performed a population-based cohort study based on participants from the UK Biobank. A multivariable Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs of incident kidney stone for blood calcium level and polygenic risk score (PRS). In addition, the potential interaction was explored. The study was conducted from January 28, 2023, through June 4, 2023. Results During the follow-up of 423,301 participants with a total of 5,490,332 person-years (median follow-up of 13.4 years), 4502 cases of kidney stone were recorded. Compared with the low blood calcium concentration group (first tertile), individuals in the high (third tertile) and moderate (second tertile) concentration groups had higher risks of kidney stone with HRs of 1.24 (95% CI, 1.15 to 1.33) and 1.11 (1.04 to 1.20), respectively. The PRS for kidney stone contained 40 independent single-nucleotide polymorphisms and was used to assign individuals to 3 groups according to the quintile. Participants with high (Q5) and moderate (Q2 to Q4) genetic risks had increased risks of kidney stone compared with low (Q1) genetic risk with HRs of 1.70 (1.53 to 1.89) and 1.31 (1.20 to 1.44), respectively. There was a joint cumulative risk of incident kidney stone between blood calcium concentration and genetic susceptibility. Conclusions Blood calcium concentration and PRS are significantly associated with incident kidney stone risk. Excessive blood calcium concentration might bring additional stone risk in populations at high genetic risk. A nonlinear correlation between blood calcium concentration and kidney stone risk was indicated.