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Abstract: TH-PO672

What the NELL-1 Does α-Lipoic Acid Have to Do with It?

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Raza, Khateeb, Corewell Health Southwest Michigan, Saint Joseph, Michigan, United States
  • Dorst, Andrew, Michigan State University College of Osteopathic Medicine, East Lansing, Michigan, United States
  • Alam, Salar, Corewell Health Southwest Michigan, Saint Joseph, Michigan, United States
  • Kwon, Katherine Westin, Corewell Health Southwest Michigan, Saint Joseph, Michigan, United States
Introduction

Membranous nephropathy, a common cause of nephrotic syndrome, is characterized by the widespread autoantibody targeting of the glomerular basement membrane and subsequent subepithelial immune complex deposition causing renal impairment. Primary Membranous Nephropathy (PMN) arises from autoantibodies against glomerular podocytes. Phospholipase A2 receptor (PLA2R) remains a predominant target, followed by Thrombospondin type-1 domain containing 7A (THSD7A). Recent studies indicate autoantibodies to Neural Epidermal Growth Factor-like 1 (NELL-1), a non-podocyte target, as a significant emerging cause of PMN. Furthermore, an association between NELL-1-associated PMN and α-lipoic acid (ALA), a common over-the-counter (OTC) antioxidant, is suggested. Herein, a case of NELL-1-positive PMN caused by ALA is described.

Case Description

An 84-year-old male with chronic kidney disease 3b/A3 and type 2 diabetes with peripheral neuropathy was evaluated by nephrology for nephrotic range proteinuria. He notably had a 15-month increase in microalbumin/creatinine ratio from 15 mg/g to 5,410 mg/g, despite therapy with SGLT2i, ARB, and GLP-1. Serum creatinine showed mild fluctuations; his exam remained without stigmata of nephrotic syndrome. Work-up for infectious, autoimmune, or malignant etiologies was unremarkable. Renal biopsy was positive for NELL-1 and negative for PLA2R or THSD7A. An in-depth review revealed an undocumented start of ALA 18 months prior by the patient in attempts to treat neuropathy refractory to maximum gabapentin dosage. Prompt discontinuation of ALA led to improved proteinuria in subsequent labs.

Discussion

NELL-1 PMN induced by ALA supplementation is a rare phenomenon seldom described in literature. Its mechanism, though not fully understood, has been proposed through the activation of autoantibodies. Classically, PMN is treated with immunosuppressive agents. In NELL-1 PMN linked to ALA use, recent literature suggests discontinuation of ALA as sufficient treatment. Contemporary trends have led to the increased use of understudied and under-recognized OTC supplements such as ALA in the treatment of neuropathy. These trends have thus necessitated heightened awareness of potential adverse effects and medication interactions. Timely recognition of adverse effects due to supplements is essential to prevent unnecessary treatment and prompt discontinuation of offending agents.