Abstract: FR-PO0739
NELL-1 Membranous Nephropathy Without Malignancy or Known Exposure: A Diagnostic Challenge in Seronegative Nephrotic Disease
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Ahmad, Hamza, Rocky Vista University, Parker, Colorado, United States
- Bates, Mitchell, Rocky Vista University, Parker, Colorado, United States
Introduction
NELL-1 associated membranous nephropathy (MN) is a rare and recently characterized subtype of MN, accounting for approximately 1.5–9.3% of cases. It is most commonly idiopathic (~50–60%) but also associated with malignancy (~30%), drug exposures (~10–15%), and rarely, systemic autoimmune diseases (<5%). We report a unique case of biopsy-confirmed NELL-1 MN in an elderly male without malignancy, known exposures, or systemic autoimmune disease, but with evolving autoimmune serologies, highlighting an atypical autoimmune-associated phenotype.
Case Description
An 81-year-old male with baseline stage 3b chronic kidney disease, mixed connective tissue disease, pseudogout, and severe arthritis presented for review of new decline in renal function and abnormal autoimmune serologies. In 2022, autoimmune testing demonstrated positive ANA (Antinuclear antibodies) with negative reflex testing. Renal function remained stable through 2025 (creatinine 1.49–1.87 mg/dL; eGFR 36–47 mL/min), and albumin was 3.1 g/dL.
A renal biopsy performed in July 2025 demonstrated subepithelial and intramembranous electron-dense deposits, podocyte foot process effacement, positive immunohistochemistry for NELL-1, PLA2R was negative. Immunofluorescent revealed strong diffuse IgG (3+) and both kappa and lambda light chain positivity. Subsequent evaluation for malignancy were unremarkable, such as CT imaging of the patient’s chest, abdomen, and pelvis were unremarkable, Prostate-Specific Antigen testing, and screening colonoscopy. A repeat ANA was 1:320 (speckled), with reflex anti-U1RNP positivity. Rheumatology referral was placed for further evaluation of mixed connective tissue disease in relation to clinical changes.
Discussion
This case illustrates a rare, non-malignant, non-exposure-associated presentation of NELL-1 MN with autoimmune serologic features. The presence of anti-U1RNP, commonly associated with Mixed Connective Tissue Disease (MCTD), raises suspicion for an evolving or limited autoimmune process. It underscores the need for a comprehensive diagnostic approach, including malignancy screening, autoimmune evaluation (with repeat testing if appropriate), and exposure history. Broader antigen testing, including NELL-1, should be pursued when traditional markers are negative to ensure accurate diagnosis, and guide appropriate treatment.