Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study

Proteinuria has been identified as prognosticator of renal outcome in patients with ANCA-associated glomerulonephritis, but whether proteinuria is related to podocyte abnormalities in these patients is largely unknown. We here investigate podocyte foot process width and number of podocytes positive...

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Main Authors: Emma E. van Daalen, Peter Neeskens, Malu Zandbergen, Lorraine Harper, Alexandre Karras, Augusto Vaglio, Janak de Zoysa, Jan A. Bruijn, Ingeborg M. Bajema
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.01405/full
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author Emma E. van Daalen
Peter Neeskens
Malu Zandbergen
Lorraine Harper
Alexandre Karras
Augusto Vaglio
Janak de Zoysa
Jan A. Bruijn
Ingeborg M. Bajema
author_facet Emma E. van Daalen
Peter Neeskens
Malu Zandbergen
Lorraine Harper
Alexandre Karras
Augusto Vaglio
Janak de Zoysa
Jan A. Bruijn
Ingeborg M. Bajema
author_sort Emma E. van Daalen
collection DOAJ
description Proteinuria has been identified as prognosticator of renal outcome in patients with ANCA-associated glomerulonephritis, but whether proteinuria is related to podocyte abnormalities in these patients is largely unknown. We here investigate podocyte foot process width and number of podocytes positive for the podocyte marker WT-1 in diagnostic renal biopsies of 25 Caucasian patients with ANCA-associated glomerulonephritis in relation to proteinuria. Control tissue was used from pre-transplantation donor kidney biopsies. Proteinuria at 10 weeks follow-up correlated significantly with foot process width (P = 0.04). Biopsies with foot process width ≥600 nm belonged more often to the crescentic or mixed class, whereas biopsies with a foot process width <600 nm were most often categorized as focal class (P = 0.03). The mean number of podocytes based upon expression of WT-1 was significantly lower in patients compared to controls (15 vs. 34 podocytes per glomerulus; P < 0.0001). The significant decrease in expression of the podocyte WT-1 marker in ANCA-associated glomerulonephritis is considered indicative of actual podocyte loss or at least, of a loss of functionality. Furthermore, our study indicates that podocyte foot process width at baseline could be indicative for proteinuria at short term follow up. For prognostic purposes, we therefore suggest to include a description of the foot process width in the diagnostic report of a biopsy with ANCA-associated glomerulonephritis.
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spelling doaj.art-ca188b4eade243399c36ead5c3c8bc342022-12-21T23:04:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01405466601Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control StudyEmma E. van Daalen0Peter Neeskens1Malu Zandbergen2Lorraine Harper3Alexandre Karras4Augusto Vaglio5Janak de Zoysa6Jan A. Bruijn7Ingeborg M. Bajema8Department of Pathology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, NetherlandsSchool of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United KingdomNephrology Department, HEGP Hospital, Assistance Publique Hôpitaux de Paris, Paris, FranceNephrology Unit, Meyer Children's Hospital and Department of Biomedical Experimental and Clinical Sciences “Mario Serio”, University of Firenze, Firenze, ItalyRenal Services, North Shore Hospital, Auckland, New ZealandDepartment of Pathology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, NetherlandsProteinuria has been identified as prognosticator of renal outcome in patients with ANCA-associated glomerulonephritis, but whether proteinuria is related to podocyte abnormalities in these patients is largely unknown. We here investigate podocyte foot process width and number of podocytes positive for the podocyte marker WT-1 in diagnostic renal biopsies of 25 Caucasian patients with ANCA-associated glomerulonephritis in relation to proteinuria. Control tissue was used from pre-transplantation donor kidney biopsies. Proteinuria at 10 weeks follow-up correlated significantly with foot process width (P = 0.04). Biopsies with foot process width ≥600 nm belonged more often to the crescentic or mixed class, whereas biopsies with a foot process width <600 nm were most often categorized as focal class (P = 0.03). The mean number of podocytes based upon expression of WT-1 was significantly lower in patients compared to controls (15 vs. 34 podocytes per glomerulus; P < 0.0001). The significant decrease in expression of the podocyte WT-1 marker in ANCA-associated glomerulonephritis is considered indicative of actual podocyte loss or at least, of a loss of functionality. Furthermore, our study indicates that podocyte foot process width at baseline could be indicative for proteinuria at short term follow up. For prognostic purposes, we therefore suggest to include a description of the foot process width in the diagnostic report of a biopsy with ANCA-associated glomerulonephritis.https://www.frontiersin.org/article/10.3389/fimmu.2019.01405/fullpodocyteproteinuriaANCAvasculitisrenal biopsy
spellingShingle Emma E. van Daalen
Peter Neeskens
Malu Zandbergen
Lorraine Harper
Alexandre Karras
Augusto Vaglio
Janak de Zoysa
Jan A. Bruijn
Ingeborg M. Bajema
Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study
Frontiers in Immunology
podocyte
proteinuria
ANCA
vasculitis
renal biopsy
title Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study
title_full Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study
title_fullStr Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study
title_full_unstemmed Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study
title_short Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study
title_sort podocytes and proteinuria in anca associated glomerulonephritis a case control study
topic podocyte
proteinuria
ANCA
vasculitis
renal biopsy
url https://www.frontiersin.org/article/10.3389/fimmu.2019.01405/full
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AT lorraineharper podocytesandproteinuriainancaassociatedglomerulonephritisacasecontrolstudy
AT alexandrekarras podocytesandproteinuriainancaassociatedglomerulonephritisacasecontrolstudy
AT augustovaglio podocytesandproteinuriainancaassociatedglomerulonephritisacasecontrolstudy
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