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Effects of phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A expression in glomerular basement membranes on treatment response and renal outcome in membranous nephropathy

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Abstract

Background

The aim of this study was to define the clinicopathologic features of phospholipase A2 receptor (PLA2R) and/or thrombospondin type-1 domain-containing 7A (THSD7A) associated membranous nephropathy(MN) focusing on their impact to disease relapse and response to treatment.

Methods

A total of 201 patients were enrolled for baseline clinical and histopathological features and 102 patients with a clinical follow-up for more than 1 year were evaluated for outcomes. Immunohistochemical staining was performed with PLA2R and THSD7A antibodies on kidney biopsies and glomerular staining was evaluated.

Results

PLA2R expression was observed in 75% of the patients’ biopsies; however, THSD7A expression was present only in 7 patients’ biopsies (3.5%). No significant difference was found between histopathological and clinical features of PLA2R positive and negative patients, collectively. Glomerular PLA2R expression was significantly associated with complete and complete/partial remission with first-line treatment; however, overall complete, and complete/partial remission rates did not differ from PLA2R negative patients (p = 0.2 and p = 0.8). Male gender, the presence of IgG4 staining and a necessity of immunosuppressive treatment were significantly associated with glomerular PLA2R expression. One patient, who developed end-stage renal disease, had glomerular expression for both PLA2R and THSD7A. Three patients with THSD7A-positive MN achieved complete remission.

Conclusions

The probability of achieving complete remission is high in patients with PLA2R-positive MN for whom the relapse rate was also higher. The overall renal outcome did not differ from PLA2R negative cases. Low incidence of THSD7A-positive MN reduces the possibility of future randomized controlled trials.

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Funding

Gazi University Internal Medicine Postgraduate Education Association and Hypertension Dialysis Transplantation Association

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Authors and Affiliations

  1. Department of Nephrology Dialysis and Transplantation, Gazi University Faculty of Medicine, 06560, Ankara, Turkey

    Hasan H. Yeter & Galip Guz

  2. Department of Pathology, Gazi University Faculty of Medicine, 06560, Ankara, Turkey

    Ipek Isik Gonul & Betul Ogut

  3. Department of Internal Medicine, Gazi University Faculty of Medicine, 06560, Ankara, Turkey

    Esra Eraslan & Ceren Karacalik

Authors
  1. Hasan H. Yeter
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  2. Ipek Isik Gonul
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  3. Esra Eraslan
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  4. Ceren Karacalik
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  5. Betul Ogut
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  6. Galip Guz
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Correspondence to Hasan H. Yeter.

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All the authors have declared that no conflict of interest exists.

Human and animal rights

The design and procedures of the study were approved by the Ethics Committee of Gazi University (Protocol ID: 37 Date: 14/01/2019) in agreement with the principles of the Declaration of Helsinki and ethical standards for human experimentation.

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Written informed consent was obtained from all participants.

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Yeter, H.H., Isik Gonul, I., Eraslan, E. et al. Effects of phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A expression in glomerular basement membranes on treatment response and renal outcome in membranous nephropathy. Clin Exp Nephrol 25, 488–500 (2021). https://doi.org/10.1007/s10157-020-02011-6

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  • DOI: https://doi.org/10.1007/s10157-020-02011-6

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