Mendelian insights: Irritable bowel syndrome as a predictor of upper urinary tract calculi

Patients with irritable bowel syndrome (IBS) have a notably higher rate of consultations in urology clinics compared to other clinics. They often present with symptoms such as lumbar pain, dysuria, and urinary difficulty that are also associated with upper urinary tract calculi (UUTC). UUTC are the leading cause of nephrectomy in non-oncological cases, early screening for high-risk populations is deemed necessary. We investigated the relationship between IBS and UUTC using a two-sample Mendelian randomization (MR) approach, with the primary analysis conducted using the inverse variance weighting method. To enhance the robustness of our findings, we conducted sensitivity analyses employing Cochran Q test, MR-Egger intercept, and MR-PRESSO. Additionally, we included type 2 diabetes in a multivariate Mendelian randomization analysis for further exploration. Our two-sample MR analysis, employing the inverse variance weighting method, suggested a positive association between IBS and UUTC, with an odds ratio of 1.47, a 95% confidence interval from 1.01 to 2.15, and a P-value of .442. Both weighted median and MR Egger analyses also indicated that IBS may be a risk factor for UUTC, although the results were not statistically significant. The Cochran Q test revealed no evidence of heterogeneity (P > .05). The MR-Egger intercept and MR-PRESSO analyses did not support the presence of pleiotropy (P > .05), and no outliers were detected by MR-PRESSO. Sensitivity analyses reinforce the reliability of our findings. Multivariate MR analysis further confirmed that IBS is a risk confirmed factor for UUTC, with significant results (P < .05). IBS is identified as one of the etiological factors for UUTC, enhancing our understanding of the gut-kidney axis. The specific mechanisms underlying this association warrant further investigation. Clinicians should consider the importance of monitoring for UUTC in patients with IBS.