Comparison of Pre- vs Post-dilution Haemodiafiltration in Children

Active, not recruiting

Lead Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Removal of low molecular weight	4 weeks	Comparison of urea and creatinine reduction ratios between pre- and post-dilution HDF modalities
Removal of nutritional markers	4 weeks	Comparison of Leptin and Ghrelin reduction ratios between pre- and post-dilution HDF modalities
Removal of protein bound uremic toxins	4 weeks	Comparison of indole acetate and p-cresyl sulphate reduction ratios between pre- and post-dilution HDF modalities
Comparison of biocompatibility by using an inflammation markers	4 weeks	Comparison of high sensitive C reactive protein, interleukin 6 and tumor necrosis factor alfa reduction ratios between pre- and post-dilution HDF modalities
Child Quality of Life (QoL) questionnaire	4 weeks	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.
Assessment of blood pressure by Ambulatory blood pressure monitoring (ABPM)	4 weeks	Comparison of systolic and diastolic blood pressures between pre- and post-dilution HDF modalities

Locations (4): Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty
🇹🇷
Istanbul, Turkey
Great Ormond Street Children's Hospital
🇬🇧
London, United Kingdom
Division of Pediatric Nephrology Hôpital Femme Mère Enfant, Hospices Civils de Lyon
🇫🇷
Lyon, Bron, France
Division of Pediatric Nephrology Center for Pediatrics and Adolescent Medicine
🇩🇪
Heidelberg, Germany