Brief Summary

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.

1.Compare endothelial dysfunction by FMD according to the stage of chronic kidney disease and in comparison to a control group without chronic kidney disease.
2.Characterize the FMD pre or post dialysis and according to the duration of the long (for example between Thursday and Sunday) vs. short (between Tuesday and Thursday) inter-dialytic period.
3.Evaluate the relationship between endothelial dysfunction according to FMD, aPL positivity and arteriovenous fistula complications in hemodialysis patients.
4.Evaluate the risk factors associated with endothelial dysfunction according to FMD, and in particular evaluate the impact of antiphospholipid antibodies.
5.Evaluate the correlation between endothelial dysfunction according to FMD and other markers of endothelial dysfunction (urinary NO and metabolites of urinary NO, PGI2, endothelin, PGH2).

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

200

participants targeted

Target at P75+ for not_applicable

Timeline

Completed

Started Oct 2023

Geographic Reach

1 country

1 active site

Status

recruiting

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Trial Relationships

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Study Timeline

Key milestones and dates

1.2 years study duration

Study Start

First participant enrolled

October 17, 2023

Completed

5 months until next milestone

First Submitted

Initial submission to the registry

March 25, 2024

Completed

10 days until next milestone

First Posted

Study publicly available on registry

April 4, 2024

Completed

9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed

Last Updated

April 4, 2024

Status Verified

April 1, 2024

Enrollment Period

1.2 years

First QC Date

March 25, 2024

Last Update Submit

April 2, 2024

Conditions

Chronic Renal Failure

Outcome Measures

Primary Outcomes (11)

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
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

Study Arms (6)

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