Circulating Testican-2 and MGT5A are Markers of Membranous Nephropathy

Sep 29, 2026

Uploaded by Theodore

Membranous nephropathy (MN) is a common cause of nephrotic syndrome, typically diagnosed by kidney biopsy. A large-scale proteomics analysis measured 6592 plasma proteins in the Boston Kidney Biopsy Cohort and replicated top associations in the NEPTUNE cohort. Testican-2 and MGT5A plasma levels increased in MN and improved discrimination versus multiple alternative diagnoses. Findings also showed corresponding glomerular gene expression changes and motivate further work on biological roles and biomarker performance alongside circulating autoantibodies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

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Introduction

Methods

Results

Conclusion

TRANSLATIONAL RESEARCH Circulating Testican-2 and MGT5A are Markers of Membranous Nephropathy Taesoo Kim 1, Wenjun Ju2, Aditya Surapaneni3, Yang Li3, Donghai Wen 1, Claire Trivin-Avillach4, Ivy A. Rosales4, Laurence H. Beck Jr5, Viji Nair2, Damian Fermin2, Jarcy Zee6, Insa M. Schmidt5, Anand Srivastava7, Ragnar Palsson 1, Isaac E. Stillman8, Matthias Kretzler2, on behalf of NEPTUNE Investigators 10 : Josef Coresh3, Sushrut S. Waikar5, Morgan E. Grams3 and Eugene P. Rhee 1,9 1Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; 2Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA; 3Division of Nephrology, Department of Medicine, New York University Langone School of Medicine, New York, New York, USA; 4Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA; 5Division of Renal Medicine, Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA; 6Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; 7Division of Nephrology, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA; 8Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; and 9Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA Introduction: Membranous nephropathy (MN) is a common cause of nephrotic syndrome usually diagnosed using kidney biopsy. Methods: We examined the association of 6592 plasma proteins with a diagnosis of MN in the Boston Kidney Biopsy Cohort (BKBC, n = 434), with replication of the top hits in the Nephrotic Syndrome Study Network (NEPTUNE, n = 132) . Results: In BKBC, 2 proteins, testican-2 and alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (MGT5A), were associated with MN when compared with the reference diagnosis (normal or thin basement membrane [TBM] disease) as well as when compared with all other diagnoses among individuals who had undergone kidney biopsy for the indication of proteinuria or nephrotic syndrome. In NEPTUNE, plasma levels of both proteins, as well as glomerular expression of their cognate genes, were increased in MN compared with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) . In receiver operating characteristic curve analyses, the addition of plasma testican-2 and MGT5A levels significantly improved discrimination of MN from other diagnoses in BKBC and NEPTUNE compared with models incorporating age, sex, race, estimated glomerular filtration rate (eGFR), and proteinuria. Conclusion: Together, these findings motivate interest in testican-2 and MGT5A as markers and potential functional participants in MN. More work is required to understand the biological role of these proteins in the glomerular basement membrane in relation to immune complex deposition as well as to assess their performance as biomarkers alongside circulating autoantibodies in patients with MN. Kidney Int Rep (2026) 11, 103695; [https://doi.org/10.1016/j.ekir.2025.11.020](https://doi.org/10.1016/j.ekir.2025.11.020) [KEYWORDS: membranous nephropathy](KEYWORDS: membranous nephropathy); MGT5A; testican-2 © 2025 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BYNC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). M N is a common cause of nephrotic syndrome, characterized on kidney biopsy by the thickening of the glomerular basement membrane, subepithelial Correspondence: Eugene P. Rhee, Massachusetts General Hospital, 165 Cambridge Street, Room 302, Boston, Massachusetts 02114, USA. E-mail: [eprhee@mgb.org](eprhee@mgb.org) 10Members of the NEPTUNE Investigators are li

FAQs

What is membranous nephropathy and how is it usually diagnosed?

Membranous nephropathy (MN) is a common cause of nephrotic syndrome. It is usually diagnosed using kidney biopsy.

How were potential blood markers identified in this study?

The study examined associations of 6592 plasma proteins with MN in the Boston Kidney Biopsy Cohort, then replicated the top findings in the NEPTUNE cohort.

Which proteins improved diagnostic discrimination for MN?

Testican-2 and MGT5A. Adding their plasma levels significantly improved discrimination of MN from other diagnoses in both cohorts.

Sep 29, 2026

Uploaded by Theodore