Multicentre comparative study of neural epidermal growth factor-like 1 protein vs M-type phospholipase A2 receptor-associated membranous nephropathy

doi:10.5527/wjn.v15.i2.118160

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World Journal of Nephrology

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2220-6124

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Nephrol. Jun 25, 2026; 15(2): 118160
Published online Jun 25, 2026. doi: 10.5527/wjn.v15.i2.118160

Multicentre comparative study of neural epidermal growth factor-like 1 protein vs M-type phospholipase A2 receptor-associated membranous nephropathy

Subrahmanian Sathiavageesan, Abirami Krishnan, Krishnaswamy Sampathkumar, Ranjanee Muthu

Subrahmanian Sathiavageesan, Department of Nephrology, Sundaram Hospital, Tiruchirappalli 620017, Tamil Nādu, India

Abirami Krishnan, Department of Nephrology, Kauvery Hospital, Salem 636201, Tamil Nādu, India

Krishnaswamy Sampathkumar, Department of Nephrology, Meenakshi Mission Hospital, Madurai 625107, Tamil Nādu, India

Ranjanee Muthu, Department of Nephrology, Apollo Hospitals, Chennai 600006, Tamil Nādu, India

Author contributions: Sathiavageesan S contributed to study conceptualization and designing, data acquisition, data visualisation, literature review, statistical analysis and prepared the first draft of the manuscript, taking responsibility as guarantor for the originality and integrity of the manuscript; Krishnan A, Krishnaswamy S and Muthu R contributed to study design, data acquisition and visualization, literature review and critically reviewed and revised the manuscript.

Institutional review board statement: This study was a retrospective observational study. None of the study components was experimental. The study was approved by the Institutional Ethics Committee of participating centres.

Informed consent statement: Not applicable because of retrospective study design.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: The data generated during this research are available with the corresponding author and can be obtained by reasonable request.

Corresponding author: Subrahmanian Sathiavageesan, MD, Chief Physician, Department of Nephrology, Sundaram Hospital, 17, EVR Road, Puthur, Tiruchirappalli 620017, Tamil Nādu, India. spssubrahmanian@yahoo.co.in

Received: December 25, 2025
Revised: January 11, 2026
Accepted: February 12, 2026
Published online: June 25, 2026
Processing time: 172 Days and 15.6 Hours

Abstract

BACKGROUND

The understanding of membranous nephropathy (MN) has significantly evolved with the discovery of novel antigenic targets. M-type phospholipase A2 receptor-associated MN (PLA2R-MN) is the most common antigenic variant, followed by neural epidermal growth factor-like 1 protein-associated MN (NELL1-MN). Few studies have directly compared the outcomes of these two variants.

AIM

To compare the outcomes of NELL1-MN with PLA2R-MN.

METHODS

In this retrospective cohort study, we compared the outcomes of NELL1-MN and PLA2R-MN using time-to-event analysis. Rate of remission - complete or partial - was the primary outcome of interest.

RESULTS

The 17 patients diagnosed with NELL1-MN during the study period were compared with 24 patients with PLA2R-MN diagnosed during the same month. Antecedent exposure to traditional indigenous medicines was more common in NELL1-MN than PLA2R-MN (70.6% vs 13%, P < 0.001). 11.8% with NELL1-MN had rheumatoid arthritis while none with PLA2R-MN had the same (P = 0.08). NELL1-MN showed a significantly higher remission-rate than PLA2R-MN (11.7 per 100-patient-months vs 5 per 100-patient-months, P = 0.01) and a shorter time-to-remission than PLA2R-MN (median: 7 months vs 13 months, P = 0.001). In multivariate Cox-regression, NELL1-MN was independently associated with a higher likelihood of remission compared with PLA2R-MN (hazard ratio = 2.65; 95% confidence interval: 1.25-5.64; P = 0.01). Spontaneous remission-rate was higher for NELL1-MN than PLA2R-MN (3.4 per 100-patient-months vs 0.3 per 100-patient-months, P = 0.01). Resistant nephrotic syndrome was more common among PLA2R-MN than NELL1-MN (2.5 per 100-patient-months vs 0 per 100-patient-months, P = 0.04).

CONCLUSION

NELL1-MN has a favourable prognosis compared to PLA2R-MN. Antigen-specific outcomes research could inform prognosis and guide treatment strategies in MN.

Keywords: Glomerulonephritis; Membranous nephroparhy; Nephrotic syndrome; Neural epidermal growth factor-like 1; M-type phospolipase A2 receptor

Core Tip: This retrospective cohort study is the first study that directly compared the outcomes of neural epidermal growth factor-like 1 protein-associated MN (NELL1-MN) with M-type phospholipase A2 receptor-associated MN (PLA2R-MN) using time-to-event analysis. NELL1-MN showed a favourable prognosis with a higher rate of remission, faster time-to-remission, more spontaneous remission and a lower rate of treatment-resistant nephrotic syndrome compared to PLA2R-MN. Additionally, this study also observed that NELL1-MN was more strongly associated with traditional indigenous medicine intake than PLA2R-MN. Antigen-specific outcomes research could inform prognosis and aid therapeutic decision-making.