Lipoic acid supplementation associated with neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy

Rebecca I Spain; Nicole K Andeen; Pamela C Gibson; Mary H Samuels; Cynthia D Morris; Andrew J Solomon; Richard Solomon; Carin Waslo; Rupali S Avasare

doi:10.1016/j.kint.2021.10.010

Lipoic acid supplementation associated with neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy

Kidney Int. 2021 Dec;100(6):1208-1213. doi: 10.1016/j.kint.2021.10.010. Epub 2021 Oct 16.

Authors

Rebecca I Spain¹, Nicole K Andeen², Pamela C Gibson³, Mary H Samuels⁴, Cynthia D Morris⁴, Andrew J Solomon⁵, Richard Solomon⁶, Carin Waslo⁷, Rupali S Avasare⁸

Affiliations

¹ Neurology Division, Portland VA Medical Center, Portland, Oregon, USA. Electronic address: spainr@ohsu.edu.
² Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, Oregon, USA.
³ Department of Pathology and Larboratory Medicine, The Robert Larner, M.D. College of Medicine at the University of Vermont, Burlington, Vermont, USA.
⁴ Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon, USA.
⁵ Department of Neurological Sciences, The Robert Larner, M.D. College of Medicine at the University of Vermont, Burlington, Vermont, USA.
⁶ Division of Nephrology and Hypertension, The Robert Larner, M.D. College of Medicine at the University of Vermont, Burlington, Vermont, USA.
⁷ Research Division, Portland VA Medical Center, Portland, Oregon, USA.
⁸ Department of Medicine, Division of Nephrology and Hypertension, Oregon Health & Science University, Portland, Oregon, USA.

Abstract

Lipoic acid (alpha lipoic acid, thioctic acid) is a popular over-the-counter antioxidant and insulin-mimetic supplement under investigation in a variety of conditions including multiple sclerosis, diabetes, and schizophrenia. Unfortunately, high-grade proteinuria was an unexpected adverse event specific to the treatment arm of our clinical trial investigating lipoic acid supplementation in patients with multiple sclerosis. This observation led to detection of similar patients in our nephrology practice. Here, we describe four biopsy-proven cases of neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy following lipoic acid supplementation and a fifth suspected case. Discontinuation of lipoic acid and supportive therapy resulted in remission.

Keywords: albuminuria; glomerulonephritis; kidney biopsy; kidney pathology; lipoic acid; membranous nephropathy; nephrotic syndrome; proteinuria.

Published by Elsevier Inc.

Publication types

Clinical Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Calcium-Binding Proteins
Dietary Supplements
EGF Family of Proteins
Glomerulonephritis, Membranous* / diagnosis
Glomerulonephritis, Membranous* / drug therapy
Humans
Proteinuria / chemically induced
Proteinuria / drug therapy
Thioctic Acid* / adverse effects

Substances

Calcium-Binding Proteins
EGF Family of Proteins
NELL1 protein, human
Thioctic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding