Evaluation of Endothelial Dysfunction Using the "Flow Mediated Dilation" Test in a Population of Chronic Renal Failure Patients at Different Stages, and Evaluation of the Role of Antiphospholipid Antibodies

Evaluation of Endothelial Dysfunction Using the "Flow Mediated Dilation" Test in a Population of Chronic Renal Failure Patients at Different Stages, and Evaluation of the Role of Antiphospholipid Antibodies - A Prospective Interventional Study.

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).

Study Overview

• Status: Recruiting
• Conditions: Chronic Renal Failure
• Intervention / Treatment: Procedure: Blood sampling; Procedure: Urine sampling; Device: Flow mediated dilatation test

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maxime Taghavi; Phone Number: 003224772644; Email: Maxime.TAGHAVI@chu-brugmann.be

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • Recruiting
    • Brugmann University Hospital
    • Contact: Maxime Taghavi, MD PhD; Email: Maxime.TAGHAVI@chu-brugmann.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients with Chronic kidney disease from stage G3a to G5
• Healthy volunteers

Exclusion Criteria:

• Patients with chronic kidney disease stage G5 with no dosage available of antiphospholipid antibodies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chronic kidney disease at stage G3a; Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 60 and 45 ml/min/1.73m²	Procedure: Blood sampling; Blood sampling; Procedure: Urine sampling; Urine sampling; Device: Flow mediated dilatation test; The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.
Experimental: Chronic kidney disease at stage G3b; Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 45 and 30 ml/min/1.73m²	Procedure: Blood sampling; Blood sampling; Procedure: Urine sampling; Urine sampling; Device: Flow mediated dilatation test; The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.
Experimental: Chronic kidney disease at stage G4; Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 30 and 15 ml/min/1.73m²	Procedure: Blood sampling; Blood sampling; Procedure: Urine sampling; Urine sampling; Device: Flow mediated dilatation test; The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.
Experimental: Chronic kidney disease at stage G5 not dialyzed; Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) less than 15 ml/min/1.73m² but not dialyzed	Procedure: Blood sampling; Blood sampling; Procedure: Urine sampling; Urine sampling; Device: Flow mediated dilatation test; The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.
Experimental: Chronic kidney disease at stage G5 with dialyze; Patients who undergo dialyze	Procedure: Blood sampling; Blood sampling; Procedure: Urine sampling; Urine sampling; Device: Flow mediated dilatation test; The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.
Active Comparator: Control; Healthy volunteer patient, without existing kidney disease	Procedure: Blood sampling; Blood sampling; Procedure: Urine sampling; Urine sampling; Device: Flow mediated dilatation test; The flow mediated dilation (FMD) test is the most commonly utilized, non-invasive, ultrasound assessment of endothelial function in humans.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Brugmann University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 4, 2024

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: Endothelial dysfunction

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No