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
- Conditions
- Chronic Renal Failure
- Interventions
- Procedure: Urine samplingProcedure: Blood samplingDevice: Flow mediated dilatation test
- Registration Number
- NCT06347029
- Lead Sponsor
- Brugmann University Hospital
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- Patients with Chronic kidney disease from stage G3a to G5
- Healthy volunteers
- Patients with chronic kidney disease stage G5 with no dosage available of antiphospholipid antibodies.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chronic kidney disease at stage G4 Flow mediated dilatation test 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 with dialyze Urine sampling Patients who undergo dialyze Chronic kidney disease at stage G4 Urine sampling Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 30 and 15 ml/min/1.73m² Chronic kidney disease at stage G4 Blood sampling Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 30 and 15 ml/min/1.73m² Chronic kidney disease at stage G3b Flow mediated dilatation test Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 45 and 30 ml/min/1.73m² Chronic kidney disease at stage G3a Urine sampling Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 60 and 45 ml/min/1.73m² Chronic kidney disease at stage G3a Blood sampling Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 60 and 45 ml/min/1.73m² Chronic kidney disease at stage G3a Flow mediated dilatation test Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 60 and 45 ml/min/1.73m² Chronic kidney disease at stage G5 with dialyze Blood sampling Patients who undergo dialyze Control Urine sampling Healthy volunteer patient, without existing kidney disease Control Flow mediated dilatation test Healthy volunteer patient, without existing kidney disease Chronic kidney disease at stage G3b Urine sampling Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 45 and 30 ml/min/1.73m² Chronic kidney disease at stage G3b Blood sampling Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) between 45 and 30 ml/min/1.73m² Chronic kidney disease at stage G5 not dialyzed Urine sampling 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 Flow mediated dilatation test Patients who undergo dialyze Chronic kidney disease at stage G5 not dialyzed Blood sampling Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) less than 15 ml/min/1.73m² but not dialyzed Control Blood sampling Healthy volunteer patient, without existing kidney disease Chronic kidney disease at stage G5 not dialyzed Flow mediated dilatation test Renal clearance according to CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) less than 15 ml/min/1.73m² but not dialyzed
- Primary Outcome Measures
Name Time Method Flow mediated dilatation test result (%) pre-intervention 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.
E-Selectine plasma level pre-intervention E-Selectine plasma level
Nitric oxide (NO) urine concentration pre-intervention Nitric oxide (NO) urine concentration
Endothelin 1 (ET-1) urine concentration pre-intervention Endothelin 1 (ET-1) urine concentration
Endothelin 1 (ET-1) plasma level pre-intervention Endothelin 1 (ET-1) plasma level
P-Selectine plasma level pre-intervention P-Selectine plasma level
Intercellular Adhesion Molecule 1 (ICAM-1) plasma level pre-intervention Intercellular Adhesion Molecule 1 (ICAM-1) plasma level
Tumour Necrosis Factor alpha (TNF alpha) urine concentration pre-intervention Tumour Necrosis Factor alpha (TNF alpha) urine concentration
Nitric oxide (NO) plasma level pre-intervention Nitric oxide (NO) plasma level
Interleukin 6 (IL-6) plasma level pre-intervention Interleukin 6 (IL-6) plasma level
Interleukin 6 (IL-6) urine concentration pre-intervention Interleukin 6 (IL-6) urine concentration
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Brugmann University Hospital
🇧🇪Brussels, Belgium