Back to Search Start Over

Minimal Change Disease Is Associated With Endothelial Glycocalyx Degradation and Endothelial Activation.

Authors :
Bauer C
Piani F
Banks M
Ordoñez FA
de Lucas-Collantes C
Oshima K
Schmidt EP
Zakharevich I
Segarra A
Martinez C
Roncal-Jimenez C
Satchell SC
Bjornstad P
Lucia MS
Blaine J
Thurman JM
Johnson RJ
Cara-Fuentes G
Source :
Kidney international reports [Kidney Int Rep] 2021 Dec 16; Vol. 7 (4), pp. 797-809. Date of Electronic Publication: 2021 Dec 16 (Print Publication: 2022).
Publication Year :
2021

Abstract

Introduction: Minimal change disease (MCD) is considered a podocyte disorder triggered by unknown circulating factors. Here, we hypothesized that the endothelial cell (EC) is also involved in MCD.<br />Methods: We studied 45 children with idiopathic nephrotic syndrome (44 had steroid sensitive nephrotic syndrome [SSNS], and 12 had biopsy-proven MCD), 21 adults with MCD, and 38 healthy controls (30 children, 8 adults). In circulation, we measured products of endothelial glycocalyx (EG) degradation (syndecan-1, heparan sulfate [HS] fragments), HS proteoglycan cleaving enzymes (matrix metalloprotease-2 [MMP-2], heparanase activity), and markers of endothelial activation (von Willebrand factor [vWF], thrombomodulin) by enzyme-linked immunosorbent assay (ELISA) and mass spectrometry. In human kidney tissue, we assessed glomerular EC (GEnC) activation by immunofluorescence of caveolin-1 ( n = 11 MCD, n = 5 controls). In vitro , we cultured immortalized human GEnC with sera from control subjects and patients with MCD/SSNS sera in relapse ( n = 5 per group) and performed Western blotting of thrombomodulin of cell lysates as surrogate marker of endothelial activation.<br />Results: In circulation, median concentrations of all endothelial markers were higher in patients with active disease compared with controls and remained high in some patients during remission. In the MCD glomerulus, caveolin-1 expression was higher, in an endothelial-specific pattern, compared with controls. In cultured human GEnC, sera from children with MCD/SSNS in relapse increased thrombomodulin expression compared with control sera.<br />Conclusion: Our data show that alterations involving the systemic and glomerular endothelium are nearly universal in patients with MCD and SSNS, and that GEnC can be directly activated by circulating factors present in the MCD/SSNS sera during relapse.<br /> (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Details

Language :
English
ISSN :
2468-0249
Volume :
7
Issue :
4
Database :
MEDLINE
Journal :
Kidney international reports
Publication Type :
Academic Journal
Accession number :
35497798
Full Text :
https://doi.org/10.1016/j.ekir.2021.11.037