S5021 Crescentic IgA Nephropathy Following Long-Term Infliximab Therapy in Crohn’s Disease

Introduction: Infliximab (IFX) is a monoclonal anti-tumor necrosis factor-α (TNF-α) antibody widely used to treat moderate-to-severe Crohn’s disease (CD). Although generally well-tolerated, rare immune-mediated adverse events have been reported, including drug-induced lupus, autoimmune hepatitis, psoriasis-like skin eruptions, vasculitis, and glomerulonephritis. We report a case of IgA nephropathy (IgAN) in a patient with CD on IFX. Case Description/Methods: A 32-year-old man with colonic and perianal CD had been maintained on long-term IFX therapy. At age 15, he underwent partial colectomy with removal of the proximal transverse to the sigmoid colon and end colostomy. Although he initially responded well to IFX, he later developed an anal stricture, requiring proctectomy at age 28. Thereafter, he remained in clinical, endoscopic, and histological remission. About 3 years post-proctectomy, he presented with fatigue and edema. Labs revealed an elevated creatinine (5.9 mg/dL [baseline ∼1.0 mg/dL]) and urinalysis showed >50 RBCs and >50 WBCs/ HPF, and 3+ proteinuria. Given rapid worsening of AKI, hemodialysis was initiated. Renal biopsy demonstrated crescentic IgA nephropathy with diffuse mesangial IgA deposition, segmental necrosis, and mild interstitial fibrosis and tubular atrophy. Serologic workup (ANA, dsDNA, ANCA, hepatitis panel) was negative. No extrarenal signs of systemic IgA vasculitis were present. Given its potential association with IgA vasculitis, IFX was discontinued. He was treated with corticosteroids and rituximab. After 6 months, his renal function improved, allowing discontinuation of hemodialysis. Follow-up colonoscopy confirmed endoscopic and histological remission off biologic therapy. Discussion: Although rare, crescentic IgAN has been linked to anti-TNF agents, including IFX and adalimumab, and notably to CD itself. Differentiating between drug-induced nephropathy and CD-related IgAN is essential. In this case, intestinal disease quiescence at AKI onset and renal recovery post-IFX cessation support a drug-provoked etiology. Proposed mechanisms include immune dysregulation from TNF-α blockade promoting aberrant IgA immune complex deposition and drug-induced autoimmunity. Management involves prompt cessation of the suspected drug, initiating immunosuppression, and optimizing supportive care. Clinicians should monitor renal function in IBD patients on long-term biologics. Awareness of this rare complication can guide timely intervention and improve outcomes.