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

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. 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. In This IssueKidney InternationalVol. 100Issue 6PreviewThe over-the-counter supplement lipoic acid (LA) is thought to be an antioxidant. Spain et al. report the unexpected development of proteinuria in 3 patients with multiple sclerosis (MS) who were receiving LA in a clinical trial for MS. Two patients had kidney biopsies and were found to have a histologic pattern of membranous nephropathy (MN), and their kidney tissue stained for neural epidermal growth factor-like 1 (NELL1). Two other patients from the investigators' nephrology clinics also developed NELL1-positive MN and were taking LA. Full-Text PDF Lipoic acid in neural epidermal growth factor-like 1–associated membranous nephropathy: more than a coincidence?Kidney InternationalVol. 101Issue 2PreviewWe found the study by Spain et al., "Lipoic Acid Supplementation Associated With Neural Epidermal Growth Factor-Like 1 (NELL1)–Associated Membranous Nephropathy," to be of great interest.1 We performed a retrospective review of medications in 115 patients with NELL1-positive membranous nephropathy (MN) compared with 200 MN cases of other antigenic types (50 cases each of phospholipase A2 receptor, thrombospondin-type 1 domain containing 7A, exostosin 1/2, and phospholipase A2 receptor/thrombospondin-type 1 domain containing 7A/exostosin/NELL1-negative MN). Full-Text PDF