Abstract: TH-PO0818
When the Cleanse Backfires: A Case of NELL-1 Membranous Nephropathy Associated with Alpha-Lipoic Acid
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
- Vardhan, Yashvi Dinesh, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
- Jain, Koyal, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
- Wyatt, Nicole Elizabeth, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Introduction
Membranous nephropathy (MN) is a leading cause of adult nephrotic syndrome. While primary MN is typically associated with antibodies against phospholipase A2 receptor (PLA2R), NELL-1 (neural epidermal growth factor-like 1) has emerged as an antigen frequently linked to secondary causes, including malignancy, drug exposure, and infections. Alpha-lipoic acid (ALA), a popular dietary supplement, has been implicated in about one-third of reported NELL-1 MN cases. Despite these associations, therapy of severe nephrotic syndrome in secondary MN remains controversial. We present a case of NELL–1–positive MN associated with ALA use and complete remission following its discontinuation.
Case Description
A 62-year-old female with well-controlled hypertension presented with progressive swelling, frothy urine, and a 20lb weight gain over several weeks. She had been taking traditional Eastern supplements, including ALA. Workup revealed nephrotic-range proteinuria (UPCR >10 mg/g), hypoalbuminemia (2.0 g/dL), and preserved kidney function (creatinine 0.7 mg/dL). Evaluation for autoimmune, infectious, malignancy, and paraprotein-related causes was unremarkable. Kidney biopsy showed stage I–II MN with subepithelial and rare mesangial deposits plus near full-house staining, raising concern for secondary etiology. She was started on low-dose tacrolimus (0.5 mg BID) while awaiting immunofluorescence staining. NELL-1 staining was positive and she was advised to discontinue all supplements. Three weeks after tacrolimus, edema resolved, and serum albumin and proteinuria improved (3.3 g/dL and 0.242 mg/mg, respectively). Tacrolimus was discontinued, and she has remained in remission for over six months without immunosuppression.
Discussion
This case highlights an increasingly recognized but underreported cause of secondary MN. As use of alternative medicines rises globally, clinicians must maintain a high index of suspicion for less common etiologies. The patient’s marked improvement after discontinuing ALA, without significant immunosuppression, and sustained remission supports a causal relationship. This case illustrates that even severe nephrotic syndrome may be managed conservatively in select patients with a defined secondary cause. Greater awareness and reporting of such cases are needed to better define the clinical course and management of non-PLA2R MN.