Acute interstitial nephritis in patients with inflammatory bowel disease treated with vedolizumab: a systematic review

Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in patients with inflammatory bowel disease (IBD) treated with the integrin inhibitor vedolizumab. Through systematic review of existing literature, we aimed to identify and describe cases of AIN in patients with IBD treated with vedolizumab. We searched Medline, Embase, Cochrane, and Web of Science Core Collection between 1 January 2009 and 25 April 2023. The search yielded 1473 publications. Titles and abstracts were screened by two independent reviewers. Seventy publications were reviewed in full-text. Eight met the inclusion criteria. Clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to two international adverse drug reaction probability assessment scales. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. Mean age at AIN onset was 36 years (range = 19–58) and the majority of patients were females (n = 6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever and malaise. Creatinine levels were elevated in all patients. Five patients sustained permanent kidney injury. Our findings suggest that vedolizumab, although rarely, could cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along with monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.</p

MOESM1 of Validating surgical procedure codes for inflammatory bowel disease in the Swedish National Patient Register

Additional file 1: Table S1. IBD-related surgical procedure codes included in the review process with frequency of validated codes; 2) Table S2. Classification and definitions of coding errors in the NPR with frequency Table S1 includes all surgical procedure codes included in the review process with frequency of validated codes. Table S2 shows the classification and definitions of coding errors used in the validation process together with frequency of identified errors

Incident arrhythmia in patients with inflammatory bowel disease and their matched reference individuals.

Incident arrhythmia in patients with inflammatory bowel disease and their matched reference individuals.</p

Flexible parametric survival model vs. Cox regression model.

Flexible parametric survival model vs. Cox regression model.</p

HR and standardized cumulative incidence of overall arrhythmias.

Upper row: HR and 95% CI of overall arrhythmias, comparing patients with IBD with their reference individuals; lower row: standardized cumulative incidence and 95% CI of overall arrhythmias in patients with IBD (pink) and their reference individuals (blue). Both HR and standardized cumulative incidence were estimated from the flexible parametric survival model. CD, Crohn’s disease; CI, confidence interval; HR, hazard ratio; IBD-U, inflammatory bowel disease unclassified; UC: ulcerative colitis.</p

Characteristics of patients with inflammatory bowel disease and their matched reference individuals.

Characteristics of patients with inflammatory bowel disease and their matched reference individuals.</p

STROBE Statement—checklist of items that should be included in reports of observational studies.

STROBE Statement—checklist of items that should be included in reports of observational studies.</p

Supplementary figures and tables.

Figure A. Hazard ratio (HR) and 95% confidence interval (CI) of specific arrhythmias, comparing inflammatory bowel disease patients with their reference individuals. Figure B. Standardized cumulative incidence and 95% CI of specific arrhythmias in inflammatory bowel disease patients (pink) and their reference individuals (blue). Table A. Previous important studies of inflammatory bowel disease and arrhythmias. Table B. International Classification of Disease (ICD) codes and SNOMED codes defining inflammatory bowel disease. Table C. ICD codes assigned for phenotypes of inflammatory bowel disease. Table D. Definitions of primary and secondary outcomes according to ICD codes. Table E. Definitions of comorbidities according to ICD codes. Table F. Definitions of prescription medications according to ATC codes. Table G. Cumulative incidence difference (95% CI) of arrhythmias during follow-up in individuals with inflammatory bowel disease, compared with their matched reference individuals. Table H. Incident overall arrhythmias in patients with inflammatory bowel disease and their matched reference individuals, stratified by sex, age at index date, calendar period, educational attainment, and number of healthcare visits. Table I. Incident overall arrhythmias in patients with inflammatory bowel disease and their matched reference individuals, stratified by the phenotypes of the Montreal Classification. Table J. Incident specific arrhythmias in patients with inflammatory bowel disease and their matched reference individuals, stratified by the phenotypes of the Montreal Classification. Table K. Sensitivity analyses of the incident arrhythmia in patients with inflammatory bowel disease and their matched reference individuals. Table L. Incident arrhythmia in patients with inflammatory bowel disease and their matched reference individuals (1-year or 3-years lag time). Table M. Characteristics of patients with inflammatory bowel disease and their IBD-free full siblings. Table N. Incident arrhythmia in patients with inflammatory bowel disease and their IBD-free full siblings. (DOCX)</p

Analysis plan.

BackgroundAlthough previous evidence has suggested an increased risk of cardiovascular disease (CVD) in patients with inflammatory bowel disease (IBD), its association with arrhythmias is inconclusive. In this study, we aimed to explore the long-term risk of arrhythmias in patients with IBD.Methods and findingsThrough a nationwide histopathology cohort, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn’s disease (CD: n = 24,954; median age at diagnosis: 38.4 years; female: 52.2%), ulcerative colitis (UC: n = 46,856; 42.1 years; 46.3%), and IBD-unclassified (IBD-U: n = 12,067; 43.8 years; 49.6%), as well as their matched reference individuals and IBD-free full siblings. Outcomes included overall and specific arrhythmias (e.g., atrial fibrillation/flutter, bradyarrhythmias, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest). Flexible parametric survival models estimated hazard ratios (aHR) with 95% confidence intervals (95% CIs), after adjustment for birth year, sex, county of residence, calendar year, country of birth, educational attainment, number of healthcare visits, and cardiovascular-related comorbidities. Over a median of approximately 10 years of follow-up, 1,904 (7.6%) patients with CD, 4,154 (8.9%) patients with UC, and 990 (8.2%) patients with IBD-U developed arrhythmias, compared with 6.7%, 7.5%, and 6.0% in reference individuals, respectively. Compared with reference individuals, overall arrhythmias were increased in patients with CD [54.6 versus 46.1 per 10,000 person-years; aHR = 1.15 (95% CI [1.09, 1.21], P P P ConclusionsIn this study, we observed that patients with IBD were at an increased risk of developing arrhythmias. The excess risk persisted even 25 years after IBD diagnosis. Our findings indicate a need for awareness of this excess risk among healthcare professionals.</div