Abstract: PUB259
Diffuse Proliferative and Crescentic Glomerulonephritis Following Anti-CTLA-4 in Complicated Rheumatoid Arthritis
Session Information
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Rai, Balaj, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Henderson, Jacob R., Mayo Clinic in Florida, Jacksonville, Florida, United States
- Yau, Amy, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Introduction
Crescentic glomerulonephritis (GN) is a rare but serious immune-related adverse event (irAE). Immune checkpoint inhibitors (ICI) may trigger de novo autoimmune GN via autoantibody formation, often dose-dependent and immune complex–mediated. We report a biopsy-confirmed case of diffuse proliferative and crescentic GN likely related to anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) therapy in a patient with complex rheumatoid arthritis (RA).
Case Description
A lethargic 46-year-old woman with RA complicated by pleural involvement, systemic lupus erythematosus, and recent abatacept reinitiation presented with NVD, anorexia, and headaches. Cr was 4.29 (baseline 1.2). Urinalysis showed AKI on CKD2 with 153 RBCs, protein 30mg/dL, 24h urine protein 2704 (A/Cr 2051mg/g, P/Cr 1.31). Labs: ANA+, dsDNA–, anti-SSA+, anti-PR3–, RF+, low C4, mildly elevated anti-MPO—suggesting mixed connective tissue disease. Prior urinalysis showed small RBCs, protein 30mg/dL (A/Cr 152mg/g, P/Cr 0.29). Treated with steroids, discharged on taper, biopsy planned.
Biopsy revealed diffuse proliferative and crescentic GN with membranoproliferative features, full-house immune deposits, and dense EM deposits (Figure 1). Treated with corticosteroids, mycophenolate mofetil, and rituximab with partial improvement.
Discussion
This case underscores ICI-induced vs. progressive autoimmune GN with immune complexes. In a meta-analysis of 45 ICI-GN cases: pauci-immune GN/vasculitis (27%), podocytopathies (20–24%), C3 GN (11%), and 41% had AIN. Early urinalysis helped prevent ESRD, more common in pauci-immune GN. Renal irAEs occur in 1.4%–4.9% on anti–CTLA-4/PD-1/PD-L1, often within 3 months. Coexisting autoimmune disease complicates diagnosis; monitoring renal function during and after ICI therapy is critical for timely intervention.