Epidemiological studies on the interplay between inflammatory bowel disease and kidney diseases
Authors: Yang Yuanhang 
Published: January 2025

<p dir="ltr">Inflammatory bowel disease (IBD) and chronic kidney disease (CKD) are chronic conditions with a bidirectional relationship influenced by immune dysregulation, chronic inflammation, and gut-kidney axis interactions. IBD, characterized by persistent gastrointestinal inflammation, is associated with kidney complications such as nephrolithiasis and interstitial nephritis, often stemming from systemic effects or adverse drug reactions. Colectomy, a surgical intervention frequently required in severe IBD cases, can lead to dehydration and electrolyte imbalances, increasing the risk of kidney damage. While biologic therapies have transformed IBD treatment by targeting specific immune pathways to reduce inflammation and induce remission, they carry potential risks, including rare kidney complications like drug-induced interstitial nephritis. The intricate interplay between IBD and CKD remains underexplored, underscoring the need for comprehensive research to improve patient care and outcomes.</p><p dir="ltr">This thesis aims to advance our understanding of the bidirectional relationship between IBD and kidney diseases through large-scale epidemiological studies utilizing real-world data.</p><p dir="ltr">Study I investigated the relationship between reduced kidney function, measured by estimated glomerular filtration rate (eGFR), and the risk of developing IBD in a large adult population. Over nearly a decade of follow-up, reduced eGFR was associated with a higher risk of IBD, particularly Crohn's disease, with stronger associations observed in women. These findings suggest that impaired kidney function may predispose individuals to IBD.</p><p dir="ltr">Study II examined the association between IBD and kidney-related complications, including CKD and acute kidney injury (AKI). Over a median 9-year follow-up, IBD patients were found to have significantly increased risks of CKD and AKI compared to non-IBD individuals. More than 10% of IBD patients developed CKD within 10 years of diagnosis, emphasizing the importance of regular kidney function monitoring and timely nephrological care.</p><p dir="ltr">Study III explored the relationship between colectomy and the risk of AKI and kidney failure in patients with biopsy-confirmed IBD within a large Swedish nationwide population. During a median follow-up of 14 years, colectomy was associated with increased risks of these kidney outcomes, particularly in patients with total colectomy, prolonged stoma periods, or ulcerative colitis. These findings highlight the need for targeted kidney function monitoring in high-risk IBD populations undergoing colectomy.</p><p dir="ltr">Study IV assessed the risk of kidney complications in IBD patients treated with vedolizumab compared to infliximab or adalimumab. Adapting a target trial emulation framework, the study revealed that vedolizumab was associated with higher risks of AKI and CKD compared to infliximab, with elevated but less pronounced risks compared to adalimumab. Younger patients were particularly vulnerable to AKI. These findings underscore the importance of close kidney function monitoring in IBD patients initiating vedolizumab therapy.</p><p dir="ltr">In conclusion, this thesis provides robust real-world evidence on the complex interplay between IBD and kidney diseases. The findings emphasize a critical need for vigilant kidney function monitoring in IBD patients, particularly those undergoing colectomy or initiating vedolizumab therapy, to improve clinical outcomes and patient care.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Yang Y,</b> Ludvigsson JF, Olen O, Sjölander A, Carrero JJ. Estimated Glomerular Filtration Rate and the Risk of Inflammatory Bowel Disease in Adults: A Swedish Population-Based Study. Inflammatory Bowel Diseases. 2024;30(5):718-725. <a href="https://doi.org/10.1093/ibd/izac267" rel="noreferrer" target="_blank">https://doi.org/10.1093/ibd/izac267</a></p><p dir="ltr">II. <b>Yang Y,</b> Ludvigsson JF, Olen O, Sjölander A, Carrero JJ. Absolute and Relative Risks of Kidney and Urological Complications in Patients With Inflammatory Bowel Disease. American Journal of Gastroenterology. 2024;119(1):138-146. <a href="https://doi.org/10.14309/ajg.0000000000002473" rel="noreferrer" target="_blank">https://doi.org/10.14309/ajg.0000000000002473</a></p><p dir="ltr">III. <b>Yang Y,</b> Ludvigsson JF, Forss A, Faucon AL, Faye AS, Olen O, Sjölander A, Carrero JJ. Risk of Kidney Failure in Patients With Inflammatory Bowel Disease Undergoing Colectomy: A Nationwide Cohort Study. Clinical Gastroenterology and Hepatology. 2024;22(11):2291-2298.e17. <a href="https://doi.org/10.1016/j.cgh.2024.05.010" rel="noreferrer" target="_blank">https://doi.org/10.1016/j.cgh.2024.05.010</a></p><p dir="ltr">IV. <b>Yang Y,</b> Forss A, Voghera S, Ludvigsson JF, Faucon AL, Sjölander A, Olén O, Carrero JJ. Adverse kidney events in patients with inflammatory bowel disease initiating biologics with vedolizumab, infliximab or adalimumab. [Manuscript]</p>