Dermal tissue remodeling and non-osmotic sodium storage in kidney patients

Abstract Background Excess dietary sodium is not only excreted by the kidneys, but can also be stored by non-osmotic binding with glycosaminoglycans in dermal connective tissue. Such storage has been associated with dermal inflammation and lymphangiogenesis. We aim to investigate if skin storage of...

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Main Authors: Ryanne S. Hijmans, Marco van Londen, Kwaku A. Sarpong, Stephan J. L. Bakker, Gerjan J. Navis, Twan T. R. Storteboom, Wilhelmina H. A. de Jong, Robert A. Pol, Jacob van den Born
Format: Article
Language:English
Published: BMC 2019-03-01
Series:Journal of Translational Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12967-019-1815-5
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author Ryanne S. Hijmans
Marco van Londen
Kwaku A. Sarpong
Stephan J. L. Bakker
Gerjan J. Navis
Twan T. R. Storteboom
Wilhelmina H. A. de Jong
Robert A. Pol
Jacob van den Born
author_facet Ryanne S. Hijmans
Marco van Londen
Kwaku A. Sarpong
Stephan J. L. Bakker
Gerjan J. Navis
Twan T. R. Storteboom
Wilhelmina H. A. de Jong
Robert A. Pol
Jacob van den Born
author_sort Ryanne S. Hijmans
collection DOAJ
description Abstract Background Excess dietary sodium is not only excreted by the kidneys, but can also be stored by non-osmotic binding with glycosaminoglycans in dermal connective tissue. Such storage has been associated with dermal inflammation and lymphangiogenesis. We aim to investigate if skin storage of sodium is increased in kidney patients and if this storage is associated with clinical parameters of sodium homeostasis and dermal tissue remodeling. Methods Abdominal skin tissue of 12 kidney patients (5 on hemodialysis) and 12 healthy kidney donors was obtained during surgery. Skin biopsies were processed for dermal sodium measurement by atomic absorption spectroscopy, and evaluated for CD68+ macrophages, CD3+ T-cells, collagen I, podoplanin + lymph vessels, and glycosaminoglycans by qRT-PCR and immunohistochemistry. Results Dermal sodium content of kidney patients did not differ from healthy individuals, but was inversely associated with plasma sodium values (p < 0.05). Compared to controls, kidney patients showed dermal tissue remodeling by increased CD68+ macrophages, CD3+ T-cells and Collagen I expression (all p < 0.05). Also, both N- and O-sulfation of heparan sulfate glycosaminoglycans were increased (all p < 0.05), most outspoken in hemodialysis patients. Plasma and urinary sodium associates with dermal lymph vessel number (both p < 0.05), whereas loss of eGFR, proteinuria and high systolic blood pressure associated with dermal macrophage density (all p < 0.05). Conclusion Kidney patients did not show increased skin sodium storage compared to healthy individuals. Results do indicate that kidney failure associates with dermal inflammation, whereas increased sodium excretion and plasma sodium associate with dermal lymph vessel formation and loss of dermal sodium storage capacity. Trial registration The cohort is registered at clinicaltrials.gov as NCT (September 6, 2017). NCT, NCT03272841. Registered 6 September 2017—Retrospectively registered, https://clinicaltrials.gov
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spelling doaj.art-15bff567091f4934b6d93bf9888dc5a62022-12-22T01:06:53ZengBMCJournal of Translational Medicine1479-58762019-03-0117111510.1186/s12967-019-1815-5Dermal tissue remodeling and non-osmotic sodium storage in kidney patientsRyanne S. Hijmans0Marco van Londen1Kwaku A. Sarpong2Stephan J. L. Bakker3Gerjan J. Navis4Twan T. R. Storteboom5Wilhelmina H. A. de Jong6Robert A. Pol7Jacob van den Born8Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenDepartment of Laboratory Medicine, University Medical Center Groningen, University of GroningenDepartment of Laboratory Medicine, University Medical Center Groningen, University of GroningenDepartment of Surgery, Division of Transplantation Surgery, University Medical Center Groningen, University of GroningenDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of GroningenAbstract Background Excess dietary sodium is not only excreted by the kidneys, but can also be stored by non-osmotic binding with glycosaminoglycans in dermal connective tissue. Such storage has been associated with dermal inflammation and lymphangiogenesis. We aim to investigate if skin storage of sodium is increased in kidney patients and if this storage is associated with clinical parameters of sodium homeostasis and dermal tissue remodeling. Methods Abdominal skin tissue of 12 kidney patients (5 on hemodialysis) and 12 healthy kidney donors was obtained during surgery. Skin biopsies were processed for dermal sodium measurement by atomic absorption spectroscopy, and evaluated for CD68+ macrophages, CD3+ T-cells, collagen I, podoplanin + lymph vessels, and glycosaminoglycans by qRT-PCR and immunohistochemistry. Results Dermal sodium content of kidney patients did not differ from healthy individuals, but was inversely associated with plasma sodium values (p < 0.05). Compared to controls, kidney patients showed dermal tissue remodeling by increased CD68+ macrophages, CD3+ T-cells and Collagen I expression (all p < 0.05). Also, both N- and O-sulfation of heparan sulfate glycosaminoglycans were increased (all p < 0.05), most outspoken in hemodialysis patients. Plasma and urinary sodium associates with dermal lymph vessel number (both p < 0.05), whereas loss of eGFR, proteinuria and high systolic blood pressure associated with dermal macrophage density (all p < 0.05). Conclusion Kidney patients did not show increased skin sodium storage compared to healthy individuals. Results do indicate that kidney failure associates with dermal inflammation, whereas increased sodium excretion and plasma sodium associate with dermal lymph vessel formation and loss of dermal sodium storage capacity. Trial registration The cohort is registered at clinicaltrials.gov as NCT (September 6, 2017). NCT, NCT03272841. Registered 6 September 2017—Retrospectively registered, https://clinicaltrials.govhttp://link.springer.com/article/10.1186/s12967-019-1815-5SodiumTransplantationKidneySkinRemodeling
spellingShingle Ryanne S. Hijmans
Marco van Londen
Kwaku A. Sarpong
Stephan J. L. Bakker
Gerjan J. Navis
Twan T. R. Storteboom
Wilhelmina H. A. de Jong
Robert A. Pol
Jacob van den Born
Dermal tissue remodeling and non-osmotic sodium storage in kidney patients
Journal of Translational Medicine
Sodium
Transplantation
Kidney
Skin
Remodeling
title Dermal tissue remodeling and non-osmotic sodium storage in kidney patients
title_full Dermal tissue remodeling and non-osmotic sodium storage in kidney patients
title_fullStr Dermal tissue remodeling and non-osmotic sodium storage in kidney patients
title_full_unstemmed Dermal tissue remodeling and non-osmotic sodium storage in kidney patients
title_short Dermal tissue remodeling and non-osmotic sodium storage in kidney patients
title_sort dermal tissue remodeling and non osmotic sodium storage in kidney patients
topic Sodium
Transplantation
Kidney
Skin
Remodeling
url http://link.springer.com/article/10.1186/s12967-019-1815-5
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