Abstract: TH-PO0778
NELL1-Positive Membranous Nephropathy Associated with Alpha-Lipoic Acid Use
Session Information
- Glomerular Case Reports: Membranous, PGN, GBM, and More
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Ahmad, Noaman, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Khan, Urooj, Hurley Medical Center, Flint, Michigan, United States
- Alsaleh, Saud Abdulelah, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Paueksakon, Paisit, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- McCall, Natalie Nesmith, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Introduction
Neural epidermal growth factor-like 1 (NELL1) is a target antigen in a subset of membranous nephropathy (MN), often linked to malignancy, drugs, or environmental exposures. Alpha-lipoic acid (ALA), a common antioxidant supplement, has recently been associated with NELL1-positive MN.
Case Description
An 83-year-old caucasian female with hypertension, type 2 DM, peripheral neuropathy, hyperlipidemia, and remote DCIS of the breast presented with progressive fatigue, peripheral edema, and rising LDL cholesterol. She reported intermittent use of alpha-lipoic acid (ALA) 600 mg twice daily for neuropathy over the past 3 years. Laboratory testing revealed nephrotic-range proteinuria (UPCR 20 mg/mg, previously 0.2) and hypoalbuminemia (2.8 g/dL, previously 4.3), with preserved renal function. Workup was notable for negative ANA, mildly elevated anti-dsDNA (86 IU/mL) with negative Crithidia luciliae IFA. PLA2R antibody was negative, complement levels were normal, and infectious and paraproteinemia screening was unremarkable. Malignancy evaluation (mammogram, colonoscopy, PET/CT) was negative. Kidney biopsy revealed features of membranous nephropathy. IF showed diffuse granular capillary loop staining for IgG (3+), C3 (2+), kappa (3+), lambda (3+), with lesser IgM (1+), IgA (trace), and C1q (trace). There was granular TBM staining. PLA2R stain was negative. EM revealed scattered subepithelial deposits, rare subendothelial deposits, and complete foot process effacement. IHC showed diffuse global granular capillary loop staining for NELL1, while EXT1/2 and THSD7A were negative. About 20% interstitial fibrosis was seen. ALA was discontinued; mycophenolate mofetil was initiated, and ACE inhibitor therapy continued. At 4 months, proteinuria improved to 7.1 g/day and serum albumin to 3.4 g/dL.
Discussion
This case highlights NELL1-associated membranous nephropathy potentially linked to chronic use of alpha-lipoic acid. Although anti-dsDNA was mildly elevated, the negative ANA and Crithidia assay, along with the absence of systemic lupus features, made a lupus-related etiology unlikely. The presence of a near full-house IF pattern, TBM staining, and rare subendothelial deposits supported a secondary form of MN. The patient clinical improvement following discontinuation of ALA and initiation of immunosuppressive therapy supports a drug-induced etiology.