Coffee and Caffeine Consumption and Risk of Kidney Stones: A Mendelian Randomization Study

Rationale & Objective: Coffee and caffeine consumption have been associated with a lower risk of kidney stones in observational studies. We conducted a Mendelian randomization study to assess the causal nature of these associations. Study Design: Mendelian randomization analysis. Setting & Participants: Independent genetic variants associated with coffee and caffeine consumption at the genome-wide significance level were selected from previously published meta-analyses as instrumental variables. Summary-level data for kidney stones were obtained from the UK Biobank study (6,536 cases and 388,508 noncases) and the FinnGen consortium (3,856 cases and 172,757 noncases). Exposure: Genetically predicted coffee and caffeine consumption. Outcome: Clinically diagnosed kidney stones. Analytical Approach: Mendelian randomization methods were used to calculate causal estimates. Estimates from the 2 sources were combined using the fixed-effects meta-analysis methods. Results: Genetically predicted coffee and caffeine consumption was associated with a lower risk of kidney stones in the UK Biobank study, and the associations were directionally similar in the FinnGen consortium. The combined odds ratio of kidney stones was 0.60 (95% CI, 0.46-0.79; P < 0.001) per a genetically predicted 50% increase in coffee consumption and 0.81 (95% CI, 0.69- 0.94; P = 0.005) per a genetically predicted 80-mg increase in caffeine consumption. Limitations: Genetic influence on kidney stone risk via pathways not involving coffee or caffeine. Conclusions: Using genetic data, this study provides evidence that higher coffee and caffeine consumption may cause a reduction in kidney stones.