Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume Overload

Cardiovascular morbidity is a major problem in patients with chronic kidney disease (CKD) and endothelial dysfunction (ED) is involved in its development. The luminal side of the vascular endothelium is covered by a protective endothelial glycocalyx (eGC) and indirect evidence indicates eGC loss in...

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Main Authors: Josephine Koch, Ryanne S. Hijmans, Manuela Ossa Builes, Wendy A. Dam, Robert A. Pol, Stephan J. L. Bakker, Hendri H. Pas, Casper F. M. Franssen, Jacob van den Born
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
CKD
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.733015/full
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spelling doaj-2c22efec536f4b079312ebfec65313ef2021-09-21T14:44:20ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.733015733015Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume OverloadJosephine Koch0Ryanne S. Hijmans1Manuela Ossa Builes2Wendy A. Dam3Robert A. Pol4Stephan J. L. Bakker5Hendri H. Pas6Casper F. M. Franssen7Jacob van den Born8Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Surgery, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDivision of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDivision of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Surgery, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDivision of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDivision of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDivision of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsCardiovascular morbidity is a major problem in patients with chronic kidney disease (CKD) and endothelial dysfunction (ED) is involved in its development. The luminal side of the vascular endothelium is covered by a protective endothelial glycocalyx (eGC) and indirect evidence indicates eGC loss in CKD patients. We aimed to investigate potential eGC loss and ED in skin biopsies of CKD patients and their association with inflammation and volume overload. During living kidney transplantation procedure, abdominal skin biopsies were taken from 11 patients with chronic kidney disease stage 5 of whom 4 were treated with hemodialysis and 7 did not receive dialysis treatment. Nine healthy kidney donors served as controls. Biopsies were stained and quantified for the eGC marker Ulex europaeus agglutinin-1 (UEA1) and the endothelial markers vascular endothelial growth factor-2 (VEGFR2) and von Willebrand factor (vWF) after double staining and normalization for the pan-endothelial marker cluster of differentiation 31. We also studied associations between quantified log-transformed dermal endothelial markers and plasma markers of inflammation and hydration status. Compared to healthy subjects, there was severe loss of the eGC marker UEA1 (P < 0.01) while VEGFR2 was increased in CKD patients, especially in those on dialysis (P = 0.01). For vWF, results were comparable between CKD patients and controls. Skin water content was identical in the three groups, which excluded dermal edema as an underlying cause in patients with CKD. The dermal eGC/ED markers UEA1, VEGFR2, and vWF all associated with plasma levels of NT-proBNP and sodium (all R2 > 0.29 and P < 0.01), except for vWF that only associated with plasma NT-proBNP. This study is the first to show direct histopathological evidence of dermal glycocalyx loss and ED in patients with CKD. In line with previous research, our results show that ED associates with markers of volume overload arguing for strict volume control in CKD patients.https://www.frontiersin.org/articles/10.3389/fcell.2021.733015/fullCKDendothelial dysfunctionNT-proBNPinflammationsodiumglycocalyx
collection DOAJ
language English
format Article
sources DOAJ
author Josephine Koch
Ryanne S. Hijmans
Manuela Ossa Builes
Wendy A. Dam
Robert A. Pol
Stephan J. L. Bakker
Hendri H. Pas
Casper F. M. Franssen
Jacob van den Born
spellingShingle Josephine Koch
Ryanne S. Hijmans
Manuela Ossa Builes
Wendy A. Dam
Robert A. Pol
Stephan J. L. Bakker
Hendri H. Pas
Casper F. M. Franssen
Jacob van den Born
Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume Overload
Frontiers in Cell and Developmental Biology
CKD
endothelial dysfunction
NT-proBNP
inflammation
sodium
glycocalyx
author_facet Josephine Koch
Ryanne S. Hijmans
Manuela Ossa Builes
Wendy A. Dam
Robert A. Pol
Stephan J. L. Bakker
Hendri H. Pas
Casper F. M. Franssen
Jacob van den Born
author_sort Josephine Koch
title Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume Overload
title_short Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume Overload
title_full Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume Overload
title_fullStr Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume Overload
title_full_unstemmed Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume Overload
title_sort direct evidence of endothelial dysfunction and glycocalyx loss in dermal biopsies of patients with chronic kidney disease and their association with markers of volume overload
publisher Frontiers Media S.A.
series Frontiers in Cell and Developmental Biology
issn 2296-634X
publishDate 2021-09-01
description Cardiovascular morbidity is a major problem in patients with chronic kidney disease (CKD) and endothelial dysfunction (ED) is involved in its development. The luminal side of the vascular endothelium is covered by a protective endothelial glycocalyx (eGC) and indirect evidence indicates eGC loss in CKD patients. We aimed to investigate potential eGC loss and ED in skin biopsies of CKD patients and their association with inflammation and volume overload. During living kidney transplantation procedure, abdominal skin biopsies were taken from 11 patients with chronic kidney disease stage 5 of whom 4 were treated with hemodialysis and 7 did not receive dialysis treatment. Nine healthy kidney donors served as controls. Biopsies were stained and quantified for the eGC marker Ulex europaeus agglutinin-1 (UEA1) and the endothelial markers vascular endothelial growth factor-2 (VEGFR2) and von Willebrand factor (vWF) after double staining and normalization for the pan-endothelial marker cluster of differentiation 31. We also studied associations between quantified log-transformed dermal endothelial markers and plasma markers of inflammation and hydration status. Compared to healthy subjects, there was severe loss of the eGC marker UEA1 (P < 0.01) while VEGFR2 was increased in CKD patients, especially in those on dialysis (P = 0.01). For vWF, results were comparable between CKD patients and controls. Skin water content was identical in the three groups, which excluded dermal edema as an underlying cause in patients with CKD. The dermal eGC/ED markers UEA1, VEGFR2, and vWF all associated with plasma levels of NT-proBNP and sodium (all R2 > 0.29 and P < 0.01), except for vWF that only associated with plasma NT-proBNP. This study is the first to show direct histopathological evidence of dermal glycocalyx loss and ED in patients with CKD. In line with previous research, our results show that ED associates with markers of volume overload arguing for strict volume control in CKD patients.
topic CKD
endothelial dysfunction
NT-proBNP
inflammation
sodium
glycocalyx
url https://www.frontiersin.org/articles/10.3389/fcell.2021.733015/full
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