Comparison of Pre- vs Post-dilution Haemodiafiltration in Children

Study Overview
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Brief Summary
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Cardiovascular morbidity and mortality are increased in children on conventional haemodialysis. Haemodiafiltration (HDF) is a newer type of dialysis which has two main types (post-dilution and predilution HDF). Post-dilution HDF is associated with better vascular health, blood pressure and growth in children. Furthermore, pre-dilution HDF is shown to remove a wider spectrum of uremic toxin compared to post-dilution HDF in adults. The investigators need more data to define the optimum dialysis modality for children.

Detailed Description
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Hypothesis: In children with end stage kidney disease pre-dilution HDF (pre-HDF) achieves improved clearances across a wide molecular weight range compared to post-dilution HDF (post-HDF). Plan of Investigation: Prevalent patients on thrice weekly HD or HDF who have a single pool Kt/v>1.2 will be randomized in to either study arm A (pre-HDF, post-HDF) or B (post-HDF, pre-HDF) after a conditioning period on post-HDF. Dialysis prescription will be kept constant during study periods including blood flow, dialysate flow, dialysate content, filter type and size. Pre-dialysis and post-dialysis bloods will be drawn at baseline and at the end of each treatment with either modality. Reduction ratios of small and middle molecular weight toxins and protein bound toxins as well as markers of inflammation and nutrition will be compared between two modalities. Assessment of blood pressure (ambulatory blood pressure monitoring) and patient wellbeing (questionnaire) will be performed at the end of each period. Children will be recruited from paediatric dialysis units in London, Istanbul Heidelberg and Lyon with extension to other centres to be confirmed. Outcomes: If the results of this study demonstrate better clearance with pre-dilution HDF compared to post-dilution HDF, this will inform a future long-term outcome study comparing different HDF modalities and will contribute to define optimum dialysis modality for children.

Official Title
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Comparison of Pre- and Post-dilution Hemodiafiltration Modalities - Effects on Biocompatibility and Solute Clearance in Children

Conditions
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Haemodiafiltration

Intervention / Treatment
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* Device: Haemodiafiltration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients treated in paediatric dialysis centres between 5-20 years of age Receiving maintenance haemodialysis with HD or HDF for the preceding 3 months In post-dilution HDF for at least 4 weeks before the start of the study Patients with stable vascular access (central line or arteriovenous fistula) and no plan to change access modality for the duration of the study Provision for ultrapure water for HDF (defined as containing <0.1 colony forming unit /ml and <0.03 endotoxin unit/ml) documented in the month prior to study start Exclusion Criteria: Incident dialysis patients (on HD or HDF for < 3 months) Patients with acute infections in the preceding 2 weeks Patients with underlying chronic inflammatory disorders (Including vasculitis) Single pool Kt/V less than 1.2 in the month prior to the study start. Children who have haemoglobin concentrations lower than 10 g/dL

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 20 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Haemodiafiltration|pre-dilution and post-dilution Haemodiafiltration|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Removal of middle molecular weight uremic toxins | The outcome measure is the difference in Beta2-microglobulin reduction ratios between pre- and post-dilution HDF treatments. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Removal of low molecular weight | Comparison of urea and creatinine reduction ratios between pre- and post-dilution HDF modalities | 4 weeks | 
| Removal of protein bound uremic toxins | Comparison of indole acetate and p-cresyl sulphate reduction ratios between pre- and post-dilution HDF modalities | 4 weeks | 
| Comparison of biocompatibility by using an inflammation markers | Comparison of high sensitive C reactive protein, interleukin 6 and tumor necrosis factor alfa reduction ratios between pre- and post-dilution HDF modalities | 4 weeks | 
| Removal of nutritional markers | Comparison of Leptin and Ghrelin reduction ratios between pre- and post-dilution HDF modalities | 4 weeks | 
| Assessment of blood pressure by Ambulatory blood pressure monitoring (ABPM) | Comparison of systolic and diastolic blood pressures between pre- and post-dilution HDF modalities | 4 weeks | 
| Child Quality of Life (QoL) questionnaire | Questionnaire including information on post-dialysis recovery time, physical activity, school or college attendance and sleep pattern will be recorded by the patient. Questionnaire will be performed at the end of each period with pre- and post-dilution HDF modality. Scale 1 to 5 - higher scores indicate better outcomes. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haemodiafiltration, Haemodialysis, Children