Uremic Toxin Removal and Hemodynamics in Long-hour Hemodialysis and Hemodiafiltration

Study Overview
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Brief Summary
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Rationale: The mortality of end-stage renal disease (ESRD) patients on dialysis remains high. This may at least be partly due to the insufficient removal of (especially protein-bound) uremic toxins which have been associated with cardiovascular morbidity and mortality. It is unknown whether the combination of long-hour haemodialysis (HD) with convection increases the removal of these toxins. Long-hour HD and long-hour haemodiafiltration (HDF) may also improve haemodynamic stability which is an important factor in treatment quality. The investigators aim to study the removal of uremic toxins in long-hour HD and HDF and to compare the haemodynamics between 4-hour and 8-hour HD and HDF. Objectives: The primary aim is to study the removal of (especially protein-bound) uremic toxins in 4-hour and 8-hour HD and HDF. A secondary aim is to compare the haemodynamic response between 4-hour and 8-hour HD and HDF.

Official Title
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Uremic Toxin Removal and Hemodynamics in Long-hour Hemodialysis and Hemodiafiltration; a Randomized Cross-over Study

Conditions
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Uremic Toxins, Haemodynamic Stability

Intervention / Treatment
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* Other: 4-hour HD, 4-hour HDF, 8-hour HD and 8-hour HDF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: prevalent conventional HD patients AV-fistula enabling double-needle vascular access with blood flow rate of at least 350 ml/min informed consent age more than 18 years Exclusion Criteria: withdrawal of consent acute intercurrent illness (infection, malignancy, cardiovascular event, uncontrolled diabetes)

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: hemodialysis patients<br>conventional hemodialysis patients | Other: 4-hour HD, 4-hour HDF, 8-hour HD and 8-hour HDF<br>* Prevalent conventional HD (CHD) patients (dialysing 3 days a week during 4 hours per dialysis session) will undergo, in random order, a mid-week 4-hour HD session, a mid-week 4-hour HDF session, a mid-week 8-hour HD session, and a mid-week 8-hour HDF session with a 2-week interval between every session to assess the influence of treatment duration and of convection on the removal of uremic toxins and on the haemodynamic responses and autonomic nervous regulation. In between the study dialysis sessions these patients will receive routine CHD treatments.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| removal of uremic toxins | To measure uremic toxin and electrolyte removal, reduction ratios, dialytic clearances and mass removal in collected dialysate will be determined. Blood samples will be taken from the inlet blood lines immediately before the onset of dialysis and at 15, 30, 60, 120, 240 minutes (4-hour and 8-hour sessions) and at 360 and 480 minutes (8-hour sessions). Furthermore, ultrafiltrate and dialysate will be continuously collected in a fractionated way. | before dialysis and at 15,30,60,120,240 minutes (4-hour and 8-hour sessions) and at 360 and 480 minutes (8-hour sessions) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| haemodynamic response | BP, heart rate, heart rate variability, cardiac output and systemic vascular resistance will be measured every 30 minutes by the Task Force Monitor. Skin microcirculation will be measured with laser Doppler flowmetry every 120 min until the end of the treatment. | every 30 minutes until end of dialysis |