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The vascular endothelium is an organ in its own right, playing, among other things, a primordial role in the control of vascular tone. This vascular tone is ensured by pro-dilator mediators (nitric oxide (NO), prostacyclins (PGI2)), or vasoconstrictors (endothelin, thromboxane A2 or PGH2).Uremic toxin accumulation in chronic kidney disease (CKD) is a well-known factor in endothelial dysfunction, often associated with higher cardiovascular risk. This association is also present for terminal chronic kidney disease characterized by the need to resort to an extra-renal purification technique (in-center hemodialysis (HD), daily home hemodialysis (HDQ), peritoneal dialysis) or to resort to renal transplantation.
For HD to be effective, it is essential that the blood flow rate passing through the dialyzer is greater than 300ml/min. This imperative requires that any hemodialysis patient have specific vascular access (dialysis catheter or arteriovenous fistula (AVF)) to ensure these flow rates. The vascular access of choice is the arteriovenous fistula , because it is associated with a lower risk of infection and lower morbidity and mortality. Making an arteriovenous fistula consists of surgically creating an anastomosis between a vein and an artery.
Complications of arteriovenous fistula are common. Arteriovenous fistula maturation may be delayed (maturation delay) or even absent. Drainage veins and/or anastomoses can also be the site of stenosis or thrombosis. The pathophysiology of these complications is complex and multifactorial. Among the risk factors for these complications (delay or absence of maturation, stenosis thrombosis), the positivity of antiphospholipid antibodies (aPL) can be cited, as well as endothelial dysfunction.
Antiphospholipid syndrome (APS) is an autoimmune disease causing a thrombotic phenotype. This is an acquired thrombophilia. In the general population, the prevalence of antiphospholipid antibodies is around 0.5%; this prevalence is far from rare in hemodialysis, since it represents up to 37% in dialysis patients. In a retrospective study carried out at Brugmann University Hospital in 2023 , on 115 patients with AVF and in whom aPL dosages were available, the prevalence of persistent positivity (2 positive dosages spaced more than 12 weeks apart) was 21%.
Interestingly, a third of the cohort presented an antibody profile that did not allow them to be classified according to the classification criteria in force. This group corresponds to patients with a single positive dosage, either not recontrolled or recontrolled negative. This group was called Fluctuating. This fluctuating group was associated with arteriovenous fistula complications in a 2019 study.
Endothelial dysfunction is also implicated in the pathophysiology of APS. In clinical practice, the "flow mediated dilation" (FMD) test makes it possible to assess endothelial dysfunction in vivo. It involves the phenomenon of post-occlusive hyperemia which is mainly linked to NO and endothelium-dependent vasodilation. In the brachial artery, NO is the sole mediator of FMD. Endothelial dysfunction according to FMD has been described in populations with advanced chronic kidney disease, as well as patients with cardiovascular diseases. Hemodialysis patients with delayed/absence of arteriovenous fistula maturation have more pathological FMDs compared to dialysis patients without fistula problems. However, the additive role of aPL in this different population has not been studied in terms of endothelial dysfunction by FMD.
The objective of this study is to evaluate the weight of antiphospholipid biology on endothelial dysfunction in hemodialysis patients, using the FMD test.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronic kidney disease at stage G3a | Experimental | Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 60 and 45 ml/min/1.73m² |
|
| Chronic kidney disease at stage G3b | Experimental | Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 45 and 30 ml/min/1.73m² |
|
| Chronic kidney disease at stage G4 | Experimental | Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 30 and 15 ml/min/1.73m² |
|
| Chronic kidney disease at stage G5 not dialyzed | Experimental | Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) less than 15 ml/min/1.73m² but not dialyzed |
|
| Chronic kidney disease at stage G5 with dialyze |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Urine sampling | Procedure | Urine sampling |
|
| Measure | Description | Time Frame |
|---|---|---|
| Nitric oxide (NO) plasma level | Nitric oxide (NO) plasma level | pre-intervention |
| Endothelin 1 (ET-1) plasma level | Endothelin 1 (ET-1) plasma level | pre-intervention |
| E-Selectine plasma level | E-Selectine plasma level | pre-intervention |
| P-Selectine plasma level | P-Selectine plasma level | pre-intervention |
| Intercellular Adhesion Molecule 1 (ICAM-1) plasma level | Intercellular Adhesion Molecule 1 (ICAM-1) plasma level | pre-intervention |
| Interleukin 6 (IL-6) plasma level | Interleukin 6 (IL-6) plasma level | pre-intervention |
| Nitric oxide (NO) urine concentration | Nitric oxide (NO) urine concentration | pre-intervention |
| Endothelin 1 (ET-1) urine concentration | Endothelin 1 (ET-1) urine concentration | pre-intervention |
| Tumour Necrosis Factor alpha (TNF alpha) urine concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Maxime Taghavi | Contact | 003224772644 | Maxime.TAGHAVI@chu-brugmann.be |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brugmann University Hospital | Recruiting | Brussels | 1020 | Belgium |
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| Experimental |
Patients who undergo dialyze |
|
| Control | Active Comparator | Healthy volunteer patient, without existing kidney disease |
|
| Blood sampling | Procedure | Blood sampling |
|
| Flow mediated dilatation test | Device | The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans. |
|
Tumour Necrosis Factor alpha (TNF alpha) urine concentration |
| pre-intervention |
| Interleukin 6 (IL-6) urine concentration | Interleukin 6 (IL-6) urine concentration | pre-intervention |
| Flow mediated dilatation test result (%) | Flow-mediated dilation (FMD) is a non-invasive vascular function test that measures the change in artery diameter in response to reactive hyperemia. The result of the test is expressed as a percentage. | pre-intervention |
| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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