Proton pump inhibitors and the risk of urolithiasis: A Mendelian randomization study

Observational studies suggest that proton pump inhibitors (PPIs) increase the risk of urolithiasis (UL). However, the causal correlation between the 2 is still unclear. To examine the causal relationship between PPIs and UL, this study used 2-sample Mendelian randomization. The genome-wide association studies (GWAS) of Omeprazole, Esomeprazole, Lansoprazole, and Rabeprazole medication can be obtained from GWAS catalog. Furthermore, we acquired UL-related single nucleotide polymorphisms from the integrative epidemiology unit OpenGWAS. To access the causality of PPIs and UL, we performed a 2-sample Mendelian randomization. The primary approach to analysis was random-effects inverse variance weighting. In addition, we also used another dataset of UL to further verify the causal role. We discovered that there was a 5% increase in the incidence of UL in the use of Rabeprazole medication (test group: odd ratio [OR] = 1.053, 95% confidence interval [CI]: 1.005-1.103; validation group: OR = 1.051, 95% CI: 1.003-1.101). Furthermore, we found that Esomeprazole was negatively correlated with UL in the inverse variance weighting method (test group: OR = 0.914, 95% CI: 0.841-0.993; validation group: OR = 0.943, 95% CI: 0.890-0.999). The results of sensitivity analyses supported our conclusion. In conclusion, our results suggest a causal relationship of PPIs to UL. For patients requiring antiacid therapy, esomeprazole may be a better option than Rabeprazole, especially in patients with high-risk factors for urolithiasis.