To dermine whether the endothelial glycocalyx is damaged by ATG therapy.
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The thickness of the endothelial glycocalyx in kidney transplant recipients
before and after ATG therapy.
Secondary outcome
The following parameters will be measured:
- Glycocalyx constituents and glycocalyx regulating enzymes: hyaluronan,
heparan sulfate, syndican-1, hyaluronidase en heparanase
- IL-6, CRP
Background summary
Cardiovascular disease is one of the major causes of morbidity and mortality
after kidney transplantation. Many of the current immunosuppressive drugs are
associated with an increase of systemic risk factors for the development of
atherosclerosis like hyperglycaemia and hypercholesterolemia. In the general
population, attention has shifted from treating systemic risk factors, towards
increasing the vasculo-protective properties of the vessel wall itself. In
recent years, it has been recognized that the endothelial glycocalyx may
contribute to the vasculo-protective properties of the vessel wall.
In experimental and human studies it has been demonstrated that inflammatory
stimuli increase the vulnerability of the vessel wall. Nieuwdorp et al. showed
recently that endotoxin challenge and subsequent cytokine release results in a
large reduction of both systemic and microvascular glycocalyx volume. Moreover,
they observed shedding of the major glycocalyx component hyaluronan, activation
of monocytes and the coagulation cascade. The influence of ATG treatment on the
endothelial glycocalyx has not been established yet. The hypothesis of the
present study is that ATG infusion will damage the endothelial glycocalyx
through the release of cytokines, contributing to an increase in vascular
vulnerability in kidney transplant recipients.
Study objective
To dermine whether the endothelial glycocalyx is damaged by ATG therapy.
Study design
A case study with interventions. Measurements of the glycocalyx will be
performed in kidney transplant recipients receiving ATG treatment because of an
allograft rejection. Patients will be admitted to the kidney transplantation
ward in the AMC as part of the standard protocol of ATG treatment. The study
will take place during the first 24 hours of ATG treatment.
Study burden and risks
The study consists of the following measurements:
- physical examination incl. blood pressure and body weight (part of standard
ATG treatment)
- measurement of the glycocalyx (3x)
- blood sampling (7 times in total; 5 times extra compared to standard ATG
treatment; total volume 56 ml)
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Female or male, age between 18 and 70 years
Kidney transplant recipient
ATG therapy because of an allograft rejection
Given written informed consent
Exclusion criteria
Smoking
Diabetes Mellitus
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL30836.018.10 |