BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
How to Identify IgA Nephropathy Presenting as Nephrotic Syndrome Coexisting with Minimal Change Disease? A 15-Year Single-Center Clinicopathological Analysis
Provisionally accepted
- 1Department of Nephrology, China-Japan Friendship Hospital, Beijing, China
- 2Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objectives Nephrotic syndrome (NS) in IgA nephropathy (IgAN) may indicate concurrent minimal change disease (MCD). This study characterized the IgAN-MCD overlap phenotype using anti-nephrin autoantibodies (IgG co-localization) in NS-IgAN patients, assessing its prevalence and therapeutic implications. Methods We conducted a retrospective analysis of 67 biopsy-confirmed NS-IgAN patients (2010-2024) with ≥1-year follow-up. Patients were stratified by treatment response into complete remission (CR, n=24) and non-remission (NR, n=26) groups. Renal biopsies were evaluated for anti-nephrin autoantibodies via IgG co-localization and podocyte ultrastructure. Longitudinal data were analyzed using repeated-measures ANOVA with Benjamini-Hochberg correction; time-to-remission was assessed by Kaplan-Meier and Cox regression analyses. Results CR patients showed significantly lower baseline serum albumin (18.8±4.0 vs. 24.1±4.2 g/L, P<0.001) and higher eGFR (101±29 vs. 62±35 mL/min/1.73m², P<0.001) compared to NR patients. Anti-nephrin IgG co-localization was detected in 54.2% of CR patients but absent in NR patients (P<0.001). Cox regression identified anti-nephrin positivity as a strong predictor of faster remission (HR: 0.40, 95% CI: 0.17-0.90; P=0.028). CR patients achieved rapid proteinuria remission (0.1±0.1 vs. 7.0±0.8 g/24h at 1 month, P<0.001) with significant time×group interactions for proteinuria (P=0.001) and serum albumin (P=0.004). An estimated 35.8% of NS-IgAN cases represented IgAN-MCD overlap. Conclusion A significant subset (~36%) of NS-IgAN patients exhibit an IgAN-MCD overlap state identifiable by renal anti-nephrin IgG co-localization, demonstrating MCD-like pathology and excellent corticosteroid response. This biomarker integration can guide personalized therapy, enabling effective short-course treatment for overlap cases while avoiding unnecessary long-term immunosuppression in classic NS-IgAN.
Keywords: IgA nephropathy, Nephrotic Syndrome, minimal change disease, Anti-nephrinautoantibodies, corticosteroid responsiveness
Received: 19 Jul 2025; Accepted: 24 Oct 2025.
Copyright: © 2025 Yang, Duan, Wang, Zhang, Xu, Zhuo and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ying Wang, christy_0707@163.com
Wen-ge Li, 15911950818@163.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.