Lipoic Acid as a Trigger for NELL-1 Positive Membranous Nephropathy

Background: Membranous nephropathy occurs when antibodies bind to antigens in the kidney’s filtering units. PLA2R is the common target antigen in the main type of MN, while NELL-1 has recently been found to be a target antigen in secondary MN. Alpha-lipoic acid, a common over-the-counter supplement for diabetic neuropathy, may trigger NELL-1-associated MN. Case Presentation: We present a case of a 69-year-old white male with type 2 diabetes, obesity (BMI 42), and diabetic peripheral neuropathy. He developed significant proteinuria after starting alpha-lipoic acid supplements (1200 mg daily) in December 2024. Before starting the supplement, his kidney function was stable (creatinine 0.87 - 0.89 mg/dL) and his urine albumin-to-creatinine ratio (UACR) was normal (less than 30 mg/g creatinine). By June 2025, about seven months after he started alpha-lipoic acid, his UACR reached 4,061 mg/g, in the nephrotic range clinically. A kidney biopsy in June 2025 confirmed membranous glomerulopathy. Tests on the biopsy showed IgG, kappa, and lambda staining in the capillary walls. PLA2R was negative, but NELL-1 was positive, confirming NELL-1-associated membranous nephropathy. The biopsy showed 23% of glomeruli globally sclerosed (3 of 13) against a background of diabetic glomerulopathy, Class IIa. The patient stopped taking alpha-lipoic acid right away and was monitored without immune-suppressing medicine. After three months, in September 2025, his UACR dropped to 2,195 mg/g. This was a 46% drop from its highest level, showing good improvement after stopping the drug. Conclusions: This case shows a link between alpha-lipoic acid supplements and NELL-1-associated membranous nephropathy. This is supported by the timing, the dosage, and the rapid improvement after stopping the drug. The case shows why it is important to monitor for protein in the urine in patients taking alpha-lipoic acid, especially at higher doses (1200 mg/day or more). Detecting this problem early and discontinuing the drug promptly can lead to significant improvement without immunosuppressive medication. Since many people use alpha-lipoic acid as a supplement, doctors should be aware of this side effect. They should consider NELL-1-associated MN in patients who develop significant proteinuria while taking this supplement.