Abstract: TH-PO704
A Novel Case of IgA Nephropathy and Tubulointerstitial Nephritis in Patients with Crohn Disease Treated with Adalimumab: What Is the Culprit?
Session Information
- Glomerular Diseases: Case Reports - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Obata, Shota, Mount Sinai Beth Israel Hospital, New York, New York, United States
- Pollack-Zollman, Martine, Mount Sinai Morningside Hospital, New York, New York, United States
Introduction
IgA nephropathy (IgAN) is associated with Crohn's disease (CD) and the use of tumor necrosis factor-alpha inhibitor (TNF-αi). Tubulointerstitial nephritis (TIN) is noted as an extra-intestinal manifestation of CD but is also reported to be caused by the use of TNF-αi. Thus, it is challenging to underpin the culprit of IgAN and TIN among patients with CD treated with TNF-αi. We present a case of IgAN concomitant with TIN in a patient with CD on adalimumab, a TNF- αi.
Case Description
A 21-year-old man with a history of CD treated with adalimumab for six years presented with a sore throat, fever, gross hematuria, and AKI (Cr 3.0 mg/dL from 0.8 mg/dL). Urinalysis revealed numerous WBCs and RBCs, rare eosinophils, negative leukocyte esterase and nitrite, and a urine protein-creatinine ratio of 3.74 g/gCr. Kidney ultrasound showed normal size and echogenicity without hydronephrosis. Immunologic and infectious workups were negative. After hydration, Cr improved to 1.8 mg/dL on discharge. He was referred for kidney biopsy, which revealed IgAN and acute tubular necrosis with acute and chronic interstitial nephritis. Adalimumab was switched to Skyrizi, an interleukin-23 (IL-23) antagonist, and losartan and prednisone 40 mg were initiated. At the last follow-up, Cr improved to 1.32 mg/dL with mild proteinuria of 0.251 g/gCr while on a slow prednisone taper.
Discussion
It is challenging to determine whether CD or TNF-αi induces IgAN and TIN. In our case, extra-intestinal manifestation is unlikely to develop, given the remission of CD. Thus, TNF-αi was switched to IL-23 antagonists in addition to administration of steroids, resulting in improved renal function and resolution of proteinuria. The mechanism of action how TNF-αi causes IgAN and TIN is unknown but may be due to an underlying predisposition to defective IgA1 structure along with altered immune regulation, auto-drug and antibody formation, and/or molecular mimicry, which together leads to immune-complex deposits in the glomeruli. Whether this is a TNF-αi class effect or specific to adalimumab needs to be determined along with the possibility of future research to determine who is at risk. It is important for gastroenterologists treating patients with CD to be aware of this risk, check baseline Cr and urinalysis, and perform regular monitoring.