Abstract: TH-PO0422
Oral Lipoic Acid Supplementation Promotes Renal Inflammation in C57BL/6 Mice
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Struthers, Hillary, Oregon Health & Science University, Portland, Oregon, United States
- McNee, Caroline, Oregon Health & Science University, Portland, Oregon, United States
- Kung, Vanderlene Liu, Oregon Health & Science University, Portland, Oregon, United States
- McCormick, James A., Oregon Health & Science University, Portland, Oregon, United States
- Avasare, Rupali S., Oregon Health & Science University, Portland, Oregon, United States
Background
The recent discovery of an association between lipoic acid use and the autoimmune disease neural EGFL-like 1 (NELL1) membranous nephropathy has raised questions regarding the mechanisms through which lipoic acid supplement use contributes to the pathogenesis of NELL1 membranous nephropathy. The cellular source of NELL1 target antigen in NELL1 membranous nephropathy is unknown. We hypothesize that lipoic acid induces podocytes to express NELL1 with lipoic acid exposure and that lipoic acid use promotes kidney inflammation.
Methods
We fed twenty male wildtype C57BL/6 mice chow supplemented with a high dose of lipoic acid (n=10) or standard control chow (n=10) ad libitum for 59 days. Fasting 12-hour urine samples were collected from metabolic cages. Kidney sections were stained with Periodic Acid Schiff and evaluated for inflammation. We used RT-qPCR to measure in vivo Nell1 expression in kidneys of lipoic acid-fed mice and control mice. In vitro, conditionally immortalized human podocytes, the neuroblastoma cell line SH-SY5Y, and HEK293 cells were exposed to lipoic acid. We used RT-qPCR to measure Nell1 expression in these three cell types. Unpaired parametric students t-tests were used to test for significant differences between groups.
Results
We report mild polyuria and mononuclear tubulointerstitial inflammation in lipoic acid-fed mice compared to control mice. No increase in kidney Nell1 expression was observed. We found no NELL1 expression in in vitro podocytes with or without lipoic acid exposure. Intriguingly, SH-SY5Y cells and HEK293 cells increased expression of Nell1 with lipoic acid exposure.
Conclusion
These data suggest that lipoic acid promotes kidney inflammation in C57BL/6 mice but does not increase expression of target antigen NELL1 in kidneys under the conditions tested. Future experiments testing non-podocyte sources of NELL1 in NELL1 membranous nephropathy is required.
Acknowledgment
I would like to acknowledge Dr. Kisho Miyasako for his mouse surgery skills, Dr. Ranjan Das for his in vitro conditionally immortalized human podocyte expertise, the lab of Dr. Randi Woltjer for embedding and sectioning mouse kidneys, Dr. Miguel Lanaspa (CU Boulder) for gifting us in vitro conditionally immortalized human podocytes, and the OHSU Histopathology Shared Resource Core.
Lipoic acid supplementation promotes renal inflammation.
Very focal, mild mononuclear tubulointersitial inflammation (black ovals) was observed on Periodic Acid Schiff-stained sections of kidneys from mice fed lipoic acid chow but not control chow. A)-C) show example sections from each of three lipoic acid-fed mice.
Funding
- NIDDK Support