The Effect of High-flux Hemodialysis and On-line Hemodiafiltration on Endothelial Function.

Study Overview
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Brief Summary
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The main aim of this project is to evaluate, in patients with chronic kidney disease (CKD5D), the role of adhesion molecules in leukocyte adhesion and transendothelial migration involved in atherogenesis. This trial is a prospective randomized crossover study in CKD5D hemodialysis patients followed in the Nephrology Unit of the Reina Sofia University Hospital (Cordoba, Spain). The estimated inclusion period is two years, with a follow-up of 24 months. Patients will be randomized to high-flux hemodialysis versus online hemodiafiltration with high convective transport (above 21 liters); after 6 months in each dialysis modality they will be switched the other technique for another 6 months. Then, patients will be maintained during 4 weeks in conventional hemodialysis wash out period, before being started in the other dialysis modality.

Detailed Description
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The main aim of this project is to evaluate, in patients with chronic kidney disease (CKD5D), the role of adhesion molecules in leukocyte adhesion and transendothelial migration involved in atherogenesis. This trial is a prospective randomized crossover study in CKD5D hemodialysis patients followed in the Nephrology Unit of the Reina Sofia University Hospital (Cordoba, Spain). The estimated inclusion period is two years, with a follow-up of 24 months. Patients will be randomized to high-flux hemodialysis versus online hemodiafiltration with high convective transport (above 21 liters); after 6 months in each dialysis modality they will be switched the other technique for another 6 months. Then, patients will be maintained during 4 weeks in conventional hemodialysis wash out period, before being started in the other dialysis modality. Patients will be stratified by age, gender and the presence of diabetes. Routine analytical determinations (urea, creatinine, sodium, potassium, chlorine, total CO2, calcium, phosphorus, FA, PTH, levels 25OH, β2m, ALT, hemoglobin, leukocytes, platelets, glucose, uric acid, total proteins, albumin , PCR, IL-6, ferritin, TSAT and homocysteine), characteristics of hemodialysis and dialysis dose (Kt / V and Kt) will be recorded. Residual renal function will be analysed every three months. In plasma, microRNAs profile and FGF23 levels will be determined. Markers of endothelial dysfunction (CD31 +, CD41-, CD144, CD62E) and subclinical atherosclerosis markers (CD11b, CD41 +) will be measured. The hospitalization and mortality rate due to cardiovascular causes and concurrent cardiovascular events throughout the study (acute myocardial infarction, stroke, transient ischemic attack and peripheral vascular disease) will be assessed along the study period.

Official Title
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Molecular Mechanisms Involved in Cell Adhesion and Migration Process: Effect of Treatment of Chronic Kidney Disease on Endothelial Dysfunction

Conditions
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Chronic Kidney Disease Requiring Chronic Dialysis

Intervention / Treatment
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* Device: on-line hemodiafiltration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Vascular access with a blood flow > 300ml/min Age >18 <80 years written informed consent Exclusion Criteria: Neoplasia B hepatitis Acute or chronic inflammation life expectance less than one year Included in living donor transplant list immunosupressive drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: prospective randomized crossover study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: high-flux hemodialysis<br>high-flux hemodialysis cut-off membrane above 50 | |
| Active Comparator: on-line hemodiafiltration<br>postdilutional on-line hemodiafiltration with a convective transport above 21 liters | Device: on-line hemodiafiltration<br>* on-line postdilutional hemodiafiltration with high convective transport above 21 liters<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of two different dialysis modalities (high flux vs online hemodiafiltration) on endothelial function markers: CD31,CD41,CD34; as measured by the percent of labeled cells obtained by flow cytometry. | These parameters will assessed, in patients with chronic kidney disease (CKD5D), Blood will be drawn before the dialysis session following the scheduled of the protocol. The measuremets of CD31 CD41 CD34 will be performend by flow cytometry according to the standard methodology described in methods. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of two different dialysis modalities ( high flux vs online hemodiafiltration) on hospitalization (hospital admission days/year). | Effect of two different dialysis modalities ( high flux vs online hemodiafiltration) on hospitalization (hospital admission days/year). Cardiovascular causes and concurrent cardiovascular events throughout the study (acute myocardial infarction, stroke, transient ischemic attack and peripheral vascular disease) will be also recorded throughout the study. | 6 months | 
| Effect of two different dialysis modalities ( high flux vs online hemodiafiltration) on Serum concentration of Fibroblast Growth Factor FGF23 (pg/ml) . | The serum concentration of Fibroblast Growth Factor FGF23 will be quantified using commercially available ELISA Kit. (pg/ml). Blood samples will be obtained before the dialysis session. | 6 months | 
| Effect of two different dialysis modalities ( high flux vs online hemodiafiltration) on vascular injury related microRNAs (relative expression) | The relative expression of microRNAs (126-3p, 223-3p,363-3p, 191-5p). will be determined by RTq-PCR. Blood samples will be obtained before the dialysis session. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Endothelial dysfunction, Atherogenesis