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

Bauer, Colin; Piani, Federica; Banks, Mindy; Ordoñez, Flor A.; Lucas-Collantes, Carmen de; Oshima, Kêichi; Schmidt, Eric P.; Zakharevich, Igor; Segarra, Alfons; Martínez, Cristina; Roncal-Jiménez, Carlos A.; Satchell, Simon C.; Bjornstad, Petter; Lucia, M. Scott; Blaine, Judith; Thurman, Joshua M.; Johnson, Richard J.; Cara-Fuentes, Gabriel

doi:10.1016/j.ekir.2021.11.037

Cited by 18 publications

(11 citation statements)

References 39 publications

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“…SARS-CoV-2 and mRNA vaccines have been associated with endothelial injury. Interestingly, recent studies have shown alterations in the glomerular endothelium in patients with MCD, suggesting that MCD associated with SARS-CoV-2 vaccination may in part be ascribed to glomerular and systemic endothelial disfunction [ 30 , 31 , 32 ]. It is worth noting that the response to the standard therapy for MCD has been suggested to be worse when it occurs around the same time as COVID-19 vaccination [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Epidemiology of Immune-Mediated Glomerulopathies before and after SARS-CoV-2 Vaccination: A Tertiary Referral Hospital Experience

Zamora

López-Martínez

Liébana

et al. 2023

JCM

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Background: Vaccination is a known trigger for the appearance of immune-mediated glomerulopathies (IMG). The appearance of IMG after SARS-CoV-2 vaccination with suspected causality has been described. Our aim is to analyze the incidence of IMG flares before and after SARS-CoV-2 vaccination in our center. Methods: All persons with native kidney biopsy (KB) from January 2019 to March 2022 in our center were included in the study. We compared the incidence of IMG before and after the start of vaccination. We also collected information about whether the patients had received a SARS-CoV-2 vaccine or have suffered from COVID in the six weeks before the IMG. We also evaluated the analytical characteristics of the outbreaks. Results: A total of 386 KB were studied. Of them, 86/218 (39.4%) were IMG performed pre- and 85/168 (50.6%) post-SV (029). The incidence of idiopathic nephrotic syndrome (INS), studied separately, was also significantly increased post-vaccination (n = 18 (10.7%)) compared to pre-vaccination (n = 11 (5%)) (p = 0.036). There were no differences in the incidence of vasculitis or IgA nephropathy. Up to 17 (20%) flares occurred 6 weeks before SARS-CoV-2 vaccination and only 2 (2.4%) within the first 6 weeks after SARS-CoV-2 infection. Within those 17 flares, the most common diagnosis was IgAN (n = 5 (29.4%)); a total of 14 (82.4%) received an mRNA vaccine and 9 (52.9%) took place after the 1st vaccine dose. There were 13 cases of minimal change disease (MCD) with debut/recurrence pre-SV and 20 MCD with debut/recurrence post-SV (p = 0.002). Conclusions: The incidence of IMG, INS and MCD flares in our center increased significantly after SARS-CoV-2 vaccination. Importantly, 20% of IMG flares took place within the first 6 weeks after receiving a vaccine dose, with the first dose being the riskiest one and IgAN the most frequent diagnosis.

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Section: Discussionmentioning

confidence: 99%

Epidemiology of Immune-Mediated Glomerulopathies before and after SARS-CoV-2 Vaccination: A Tertiary Referral Hospital Experience

Zamora

López-Martínez

Liébana

et al. 2023

JCM

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“…A recent study on such changes ( 23 ) has demonstrated that in addition to changes in podocytes, the disappearance of endothelial cell fenestrations and the disappearance of the cytoplasmic honeycomb sieve structure of endothelial cells is also visible, and it is believed that patients with changes in endothelial cells might have a poor prognosis. Bauer et al ( 24 ) suggested that alterations involving the systemic and glomerular endothelium are nearly universal in patients with MCD, and that Glomerular endothelial cell can be directly activated by circulating factors present in the MCD sera during relapse. The above literature suggests that in terms of the pathological changes in kidneys in NS, in addition to foot process effacement, changes in endothelial cells and the basement membrane may also be involved in the pathogenesis and process of NS.…”

Section: Discussionmentioning

confidence: 99%

Study on the relationship between nephrotic syndrome and atopic diseases in childhood

Zheng

Hou

et al. 2022

Front. Pediatr.

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ObjectiveThe present study aimed to explore the relationship between nephrotic syndrome and atopic diseases in childhood.MethodsFrom 2018 to 2019, 234 children with first-onset primary nephrotic syndrome (PNS) were selected for observation and long-term follow-up, and the clinical and laboratory data. To compare the levels of total serum IgE, histamine and bradykinin of the same children at the time of first onset, remission and relapse of PNS. The extent of podocyte foot process effacement was compared between the urinary protein negative-conversion group and the proteinuric group with the NS range. The correlation between the urine protein quantification and the extent of foot process effacement was also observed.Results(1) The mean age of 234 children with first-onset PNS was 4.82 ± 3.63 years, with a male to female ratio of 162/72. (2) There were 109 cases (46.58%) with concomitant atopic diseases (AD) and 151 cases (64.53%) with elevated levels of total serum IgE. There were 136 cases with recurrence during the follow-up, of which recurrence due to allergy-related factors was greater than that due to infection-related factors. (3) The total IgE and bradykinin serum levels were significantly higher in children with first-onset PNS and recurrent PNS compared with those in remission, and the differences were statistically significant (P < 0.05). The level of histamine in children with first-onset PNS was higher than that in children with remission (P < 0.05), and there was no significant difference in the level of histamine between children in the recurrence group and those in the remission group (P > 0.05). (4) There was no significant difference in the extent of foot process effacement between the urinary protein negative-conversion group and the proteinuric group with the NS range. There was no significant correlation between the proteinuria quantification and the extent of foot process effacement.ConclusionThere existed a high co-morbidity with AD in children with PNS, and allergy-related factors might be an important recurrence factor in children with PNS. The injury to the filtration barrier in MCD might not only be correlated with podocyte lesions but also with some serum permeability factors. Serum IgE, histamine, and bradykinin might be the plasma permeability factors in children with PNS.

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“…damage [17]. Similarly, acute kidney damage with transient proteinuria could be caused by locally activated heparinases in kidney that degrade the glycocalyx leading to a diminished glomerular filtration barrier and vascular leakage [18 & ].…”

Section: Kidney Diseasementioning

confidence: 99%

“…When the glomerular endothelial glycocalyx is damaged, the endothelium and podocytes are exposed to the circulating factors within the blood, leading to albuminuria [16]. Indeed, patients with podocyte disorders have an increase in syndecan-1, heparin sulfate in the blood, as well as enhanced heparinase activity, indicating glycocalyx degradation [17]. Glycocalyx degradation in these conditions is accompanied by von Willebrand factor and thrombomodulin release into the blood that may also contribute to podocyte damage [17].…”

Section: Kidney Diseasementioning

confidence: 99%

Therapeutic strategies targeting the endothelial glycocalyx

Machin

Sabouri

Zheng

et al. 2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review This review will highlight recent studies that have examined the endothelial glycocalyx in a variety of health conditions, as well as potential glycocalyx-targeted therapies. Recent findings A degraded glycocalyx is present in individuals that consume high sodium diet or have kidney disease, diabetes, preeclampsia, coronavirus disease 2019 (COVID-19), or sepsis. Specifically, these conditions are accompanied by elevated glycocalyx components in the blood, such as syndecan-1, syndecans-4, heparin sulfate, and enhanced heparinase activity. Impaired glycocalyx barrier function is accompanied by decreased nitric oxide bioavailability, increased leukocyte adhesion to endothelial cells, and vascular permeability. Glycocalyx degradation appears to play a key role in the progression of cardiovascular complications. However, studies that have used glycocalyx-targeted therapies to treat these conditions are scarce. Various therapeutics can restore the glycocalyx in kidney disease, diabetes, COVID-19, and sepsis. Exposing endothelial cells to glycocalyx components, such as heparin sulfate and hyaluronan protects the glycocalyx. Summary We conclude that the glycocalyx is degraded in a variety of health conditions, although it remains to be determined whether glycocalyx degradation plays a causal role in disease progression and severity, and whether glycocalyx-targeted therapies improve patient health outcomes. Future studies are warranted to investigate therapeutic strategies that target the endothelial glycocalyx.

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

Cited by 18 publications

References 39 publications

Epidemiology of Immune-Mediated Glomerulopathies before and after SARS-CoV-2 Vaccination: A Tertiary Referral Hospital Experience

Epidemiology of Immune-Mediated Glomerulopathies before and after SARS-CoV-2 Vaccination: A Tertiary Referral Hospital Experience

Study on the relationship between nephrotic syndrome and atopic diseases in childhood

Therapeutic strategies targeting the endothelial glycocalyx

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