Severe kidney involvement in a case of very early onset inflammatory bowel disease

Enrico Drago^1,2*Roberta Carfora¹Barbara Cafferata³Gabriele Gaggero³Laura Puzone¹Edoardo La Porta⁴Sara Signa⁵Paolo Gandullia⁵Valerio Gaetano Vellone³Andrea Angeletti⁴Serena Arrigo⁵

• ¹Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Università degli Studi di Genova, Genova, Italy
• ²UOC Reumatologia e Malattie Autoinfiammatorie, IRCCS Istituto Giannina Gaslini, Genova, Italy
• ³Pathology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy
• ⁴Division of Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, Genova, Italy
• ⁵Pediatric Gastroenterology and Endoscopy Unit, IRCSS Istituto Giannina Gaslini, Genova, Italy

Background: Patients affected by very early onset inflammatory bowel disease (VEO-IBD) are frequently refractory to standard treatments. Despite the lack of randomized clinical trials, vedolizumab emerged as an effective and safe alternative treatment in VEO-IBD resistant to TNF-antagonist. We here present a case of VEO-IBD with ulcerative colitis (UC) phenotype developing renal injury after vedolizumab administration. Case presentation: An 11-year-old female patient with VEO-UC was referred to our clinic for fever, nausea, and fatigue. She has been treated with vedolizumab for one year due to steroid-dependent disease and failure of multiple therapies, including anti-TNF agents. At admission, she was in steroid-free clinical and endoscopic remission, with leukocytosis, increased inflammatory markers and a raise in serum creatinine. Urine samples revealed persistent leukocyturia over the past 8-10 months with the absence of lower urinary tract symptoms and negative serial urine culture. MRI showed swollen-looking kidneys with bilateral irregular DWI signal restriction. Kidney biopsy revealed the presence of acute tubular damage with a mixed interstitial inflammatory infiltrate consistent with drug-induced acute tubulointerstitial nephritis (TIN). After prompt start of systemic glucocorticoid therapy and temporary discontinuation of vedolizumab, normalization of renal function and urinalysis was observed. Vedolizumab was restarted after 2 months, pre-medicated with steroid. The follow-up renal biopsy performed after 6 months showed a regression of the histological pattern, with chronic signs characterized by mild tubular atrophy and interstitial fibrosis. Conclusion: Vedolizumab-related acute TIN is a potentially severe complication, rarely described in adult patients. We report the first case of VEO-IBD with a probable vedolizumab-related acute TIN, treated with corticosteroids, with a good response and maintenance of vedolizumab. Persisting sterile leukocyturia could represent an early sign.