Acute Interstitial Nephritis Is a Potential Adverse Effect in Inflammatory Bowel Disease Patients Treated With Vedolizumab: A Case Report and Review of the Literature

Abstract

We report a case of vedolizumab (VDZ)-associated acute interstitial nephritis (AIN) in a 44-year-old man with refractory ulcerative colitis. The case highlights the need for nephrotoxicity monitoring in patients receiving VDZ for inflammatory bowel disease, as well as the inherent difficulties in recognizing AIN in this clinical setting. 4 months after starting VDZ therapy, the patient was admitted with dyspnoea and chest pain. Although investigations for suspected pulmonary embolism were negative, evidence of acute kidney injury was found and a kidney biopsy showed AIN. Identification of the causative role of VDZ was confounded by the fact that the patient was also being treated with omeprazole, which was considered to be the likely cause of AIN. However, rechallenge with VDZ in the absence of omeprazole again led to worsening kidney function that improved when the VDZ was stopped. The presumed recurrence of VDZ-associated AIN occurred during a tapering course of oral prednisolone. This case adds to the literature by reporting detailed tracking of a dechallenge-rechallenge sequence that provides convincing evidence of VDZ-induced AIN. These findings underscore the need for renal surveillance during VDZ therapy to prevent potential progression to chronic kidney disease.

Introduction

Acute interstitial nephritis (AIN) is a common cause of acute kidney injury. The majority of cases are drug induced, often triggered by nonsteroidal anti-inflammatory drugs, antibiotics, and, increasingly, biological immune response modifiers such as monoclonal antibodies. It is thought that drug deposition in the renal interstitium triggers an immune response, with a drug either being directly immunogenic or binding to a host protein to form an immunogenic hapten-carrier complex.¹ Induction of an immune response leads to inflammation, involving recruitment of leukocytes such as lymphocytes, monocytes/macrophages, and eosinophils, complement activation, and release of cytokine mediators that drive the inflammatory process.

There is emerging evidence of an association between AIN and vedolizumab (VDZ), a drug used to treat refractory inflammatory bowel disease (IBD). VDZ is a humanized monoclonal antibody that targets α4β7 integrin, a heterodimeric protein on the surface of lymphocytes that facilitates their migration into gut tissue by interacting with mucosal addressin cell adhesion molecule-1 expressed on the endothelial cells of intestinal blood vessels. By blocking this interaction, VDZ prevents immune cells, particularly effector memory T cells, from entering the gut mucosa, thereby reducing intestinal inflammation without significantly suppressing systemic immunity.² Following clinical trials, including the GEMINI program,^3,4 VDZ is regarded as an effective and generally safe treatment for IBD.

In this study, we report a case in which AIN developed in close temporal association with the use of VDZ in ulcerative colitis (UC), including presumed recurrence of AIN following VDZ rechallenge. The case provides convincing longitudinal evidence that AIN is a potential adverse effect of VDZ and highlights the diagnostic challenges of recognizing and managing drug-induced kidney injury in patients with refractory IBD.

Case Presentation

A 44-year-old man was referred to the nephrology department owing to a documented decline in his kidney function between April and August 2024. There was a long-standing history of UC, along with asthma and Wolff-Parkinson-White syndrome.

The symptoms of UC began in 2000. A colonoscopy in 2010 confirmed a diagnosis of pan-UC, with inflammation extending from the rectum to the caecum. The maintenance treatment regimen included mesalazine and azathioprine, supplemented by prednisolone during flare-ups. Anti-TNF-alpha therapy with infliximab was started in April 2015, followed by maintenance infusions every 6-8 weeks. The patient was subsequently treated with adalimumab in July 2020, followed by ustekinumab in April 2021, filgotinib in December 2022, and ozanimod in August 2023. These agents were all ultimately stopped because of a lack of effectiveness. The patient then began treatment with VDZ, with the first loading dose (300 mg) being administered intravenously in late March 2024, followed by 2 additional loading doses in April 2024 and May 2024.

In April 2024, the patient was admitted to the hospital with shortness of breath and right-sided lower chest pain. Computed tomography pulmonary angiography confirmed pulmonary embolism, for which anticoagulation was started with apixaban. He recovered from this episode without any side effects. In June 2024, the proton pump inhibitor omeprazole was introduced for apixaban-induced gastritis to prevent bleeding from the upper gastrointestinal tract.

In August 2024, just over 4 months after administering VDZ, the patient was again admitted with symptoms of dyspnoea and chest pain. There was no evidence of further pulmonary embolism to explain these symptoms. Instead, it was found that the patient’s kidney function had declined substantially since April 2024 (Fig 1). Blood investigations showed evidence of acute kidney injury, with elevated serum levels of creatinine (200 μmol/L) and urea (7.6 mmol/L). The creatinine levels were almost double the baseline values before the commencement of VDZ treatment. The estimated glomerular filtration rate was reduced to 35 mL/min/1.73 m², less than half the baseline value of 72 mL/min/1.73 m². Other laboratory findings included elevated C-reactive protein (78 mg/L) and reduced levels of albumin (30 g/L) and hemoglobin (100 g/L). White blood cells (4 × 10⁹/L) and lymphocytes (1 × 10⁹/L) were at the lower limit of normal, with neutrophils (2.68 × 10⁹/L) and eosinophils (0.2 × 10⁹/L) within the normal range. Blood screens for autoimmune disease, multiple myeloma, and hepatitis were negative.

Figure 1.

Changes in kidney function, as evidenced by trends in serum creatinine concentration and eGFR, in relation to the use of VDZ and omeprazole. The x-axis label shows the units and normal range for each parameter measured. Abbreviations: eGFR, estimated glomerular filtration rate; VDZ, vedolizumab.

Kidney biopsy was done to investigate the cause of acute kidney injury. This showed features of AIN, with edema and a dense mixed inflammatory cell infiltrate in the renal interstitium (Fig 2). Omeprazole and VDZ were discontinued owing to concerns regarding their possible nephrotoxicity. There were no other medications that could potentially have been associated with AIN. The H₂-receptor antagonist famotidine treatment was started as an alternative to omeprazole, and oral prednisolone (30 mg/d) treatment was commenced. By September 2024, the patient reported feeling well, with an improved estimated glomerular filtration rate of 47 mL/min/1.73 m² (Fig 1). VDZ was reintroduced, as omeprazole was considered to be the most probable contributor to AIN. The oral prednisolone (30 mg/d) treatment was maintained, followed by tapering by 5 mg/d per wk beginning in October 2024. In November 2024, the patient started to feel unwell again, with symptoms of fatigue and shortness of breath. His kidney function showed evidence of decline from late October (ie, during the period of prednisolone tapering), with an estimated glomerular filtration rate of 35 mL/min/1.73 m² in late November 2024 (Fig 1). VDZ was now suspended as it was considered to be the cause of the presumed AIN recurrence, given that the patient was no longer taking any proton pump inhibitor. Oral prednisolone was re-escalated to 30 mg/d. The estimated glomerular filtration rate started improving gradually, reaching 44 mL/min/1.73 m² by January 2025. There were also reductions in serum creatinine concentration (Fig 1), and the patient reported feeling better. His colitis symptoms were managed with corticosteroids, pending evaluation for colectomy as a treatment option.

Figure 2.

Histopathological images of the kidney biopsy stained with (A) hematoxylin and eosin and (B) periodic acid--Schiff. The renal interstitium is edematous and contains a dense, diffuse infiltrate of inflammatory cells, with lymphocyte infiltration of tubular epithelium. Arteriolar walls are expanded by hyaline material (staining magenta with periodic acid--Schiff), indicating arteriolar hyalinosis. Magnification: x100.

Discussion

This case emphasizes the importance of vigilance for nephrotoxicity when using VDZ to treat IBD. It also illustrates that diagnosing AIN in this setting may be challenging, owing to nonspecific clinical features, the existence of comorbid conditions, or the use of confounding medications. As in the case reported in this study, AIN often presents with vague general symptoms, which may include fever, tiredness, or flank pain. Especially in the early stages, these symptoms may be mistaken for consequences of other disorders affecting patients with IBD, including dehydration, infection, or active bowel inflammation.⁵ Kidney damage caused by biologic agents is frequently missed, as regular monitoring for such side effects is not always included in treatment plans. Definitive diagnosis of AIN requires a kidney biopsy,⁶ yet this procedure is not always performed in a timely manner. Prompt diagnosis and treatment of AIN is required to prevent activation of fibroblasts in the renal interstitium, leading to fibrosis, tubular atrophy, and progression to chronic kidney disease.¹

The strong temporal association that we observed between biopsy-proven AIN and the administration of VDZ argued strongly that VDZ was the cause of AIN. There was no good evidence to support alternative possible causes, such as infection⁷ or an extraintestinal manifestation of UC.⁸ We initially considered omeprazole the likely cause of AIN, given the well-known association of this drug with interstitial nephritis.⁹ However, the deterioration of the patient’s kidney function after rechallenge with VDZ in the absence of omeprazole, combined with the improvement in kidney function when the VDZ treatment was stopped (both initially and following rechallenge), provided a convincing demonstration that this drug was the cause of AIN. Our case therefore adds to the literature by providing strong evidence for VDZ-induced AIN, based on detailed longitudinal tracking of a complete dechallenge-rechallenge sequence, with clear separation of potentially confounding drug effects.

Existing literature on VDZ-induced AIN is limited. By November 2025, of the 66,106 reports concerning VDZ in WHO VigiAccess (www.vigiaccess.org), only 104 (0.2%) concerned tubulointerstitial nephritis. There has been a small number of reports describing the occurrence of AIN following administration of VDZ in IBD (Table 1). These show that AIN may develop in a range of clinical settings, with considerable variability in the time to onset—ranging from a few days to ∼12 months of maintenance treatment10, 11, 12, 13, 14 (Table 1). Together, these reports highlight the importance of early and sustained vigilance for the possibility of nephrotoxicity following the commencement of VDZ therapy.

Table 1.

Summary of Reported Cases of Vedolizumab-Induced Acute Interstitial Nephritis

Case Report	Patient Demographics	Underlying Condition	Time to Onset of AIN	Rechallenge Attempted	Rechallenge Outcome	Biopsy Confirmed?	Notes
Present case	44 M	Ulcerative colitis	∼4 mo	Yes (with steroids)	Recurrence	Yes	AIN reversible with withdrawal of VDZ
Bailly et al10	55 F	Crohn disease	∼6 d	Yes (with steroids)	No recurrence	Yes	Symptoms began “a few hours” after commencing VDZ; successful VDZ rechallenge with steroid prophylaxis
O’Leary et al11	Man in his 20s	Ulcerative colitis	∼6 mo	Yes (with steroids)	Recurrence and persistent impairment	Yes	Steroid prophylaxis failed; development of stage 2 CKD
Ogata et al12	34 M	Kidney transplant with post-transplant ulcerative colitis	∼11 d	No	N/A	Yes	Highlighted risk of AIN in immunosuppressed transplant patient
Simpson et al13	44 F	Crohn disease	∼12 mo	No	N/A	Yes	First case reporting AIN secondary to VDZ maintenance
Subhaharan et al14	20 M	Ulcerative colitis	∼10 mo	No	N/A	Yes	Full recovery after VDZ withdrawal and steroid treatment

Abbreviations: AIN, acute interstitial nephritis; CKD, chronic kidney disease; F, female; M, male; N/A, not applicable; VDZ, vedolizumab.

The presumed recurrence of AIN after VDZ rechallenge in our patient occurred during a course of tapering oral prednisolone. Although it has been reported that rechallenging with VDZ alongside prophylactic steroids successfully prevented AIN recurrence,¹⁰ another case saw failure of rechallenge with steroid prophylaxis, leading to the progression to chronic kidney disease.¹¹ A further case reported the development of AIN in a patient with a kidney transplant who was receiving maintenance immunosuppression therapy with a calcineurin inhibitor.¹² The value of steroid prophylaxis in preventing VDZ-induced nephrotoxicity therefore remains uncertain.

In conclusion, this case provides detailed longitudinal evidence that AIN is a clinically significant potential adverse effect of VDZ therapy, even when IBD is effectively controlled. Awareness of this risk is essential to avoid delayed diagnosis of acute kidney injury, which may otherwise progress to chronic kidney disease. Timely withdrawal of VDZ is associated with improved kidney function, suggesting that nephrotoxicity is at least partially reversible. Balancing effective disease control with the potential risk of drug-induced kidney injury continues to pose a clinical challenge in the management of IBD.