Comparison of Post- and Pre-dilutional Hemodiafiltration in Hemodialysis Patients

Study Overview
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Brief Summary
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Hemodiafiltration (HDF) is a choice of treatment modalities for patients with end-stage renal disease. Hemodiafiltration, combining diffusion and convection, may increase removal of large and middle molecule uremic toxins comparing to conventional hemodialysis. The techniques of hemodiafiltration include pre-dilution and post-dilution according to the infusion site of substitution fluid. Post-dilution HDF is most widely used because of higher removal rate of uremic toxins. However, hemoconcentration and clotting of membrane limit its further clearance of toxins. Pre-dilution may preserve membrane permeability and maintain hemodynamic status. Although lower clearance of small molecule uremic toxins, one study in Japan showed survival benefits of pre-dilution HDF, comparing to post-dilution HDF. The aim of this study was to compare pre-dilution and post-dilution HDF in terms of their clinical and biological parameters and clearance of uremic toxins by using cross-over study design.

Detailed Description
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Study design: randomly assigned, cross-over study. Patient number: 60. Inclusion criteria: stable patients end-stage renal disease who were older than 20 years and received thrice-weekly standard hemodialysis for more than 3 months were recruited. Exclusion criteria: active systemic disease, liver cirrhosis, active malignancy, receiving immunosuppressive treatment, dialysis with temporal non-tunneled catheter, inadequate dialysis dose (single-pooled Kt/V<1.2). Methods: Prior to randomization, a Charlson Comorbidity Index score and baseline characteristics are recorded for each patient. Each patient who received HDF prior to study will received one-month high-flux hemodialysis with target single-pooled Kt/V>1.2 for washout. The baseline characteristics of each patient including dialyzer, dialysis time, blood flow, dialysate flow, replacement volume, pre- and post-dialysis blood pressure and body weight were recorded. The follow-up laboratory data will also be collected: predialysis C-reactive protein, blood urea nitrogen, creatinine, bicarbonate, sodium, potassium, uric acid, albumin, calcium, phosphate, intact parathyroid hormone, β2-microglobulin, prolactin, fibroblast growth factor 23, α1-microglobulin, indoxyl sulfate, p-cresol sulfate, advance oxidation protein products, advance glycation product, percentage of proinflammatory monocytes; interleukin-6, tumor necrosis factor-α, hematocrit, transferrin saturation and ferritin. Urea kinetics including kt/V, Urea reduction ratio and normalized protein catabolic rate are calculated. We also used Physical Symptoms Distress Scale for life quality measurement. After randomization, two group received standard prescription of pre- and post-dilution HDF. The prescribed convective volume per treatment of post-dilution mode is based on blood flow, filtration fraction and hematocrit to achieved current recommendation of 23 liter/1.73m2. The convective volume of pre-dilution mode will be at least twice higher than the desired dose in post-dilution mode for each patient. After 3-month stable hemodiafiltration, parameters mentioned above will also be checked. Two group will be switched for another 3-month course and then switch again. The total following time is 12 months. Outcome: The primary objective is to compare the removal of a wide spectrum of solutes such as middle and protein-bound molecules. Secondary outcomes are intradialytic tolerance, including intradialytic hypotension, cramps and arrhythmia, and life quality measurements.

Official Title
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Effects of Post- and Pre-dilutional Hemodiafiltration on Patients With End-stage Renal Disease

Conditions
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Hemodiafiltration

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: stable patients end-stage renal disease who were older than 20 years and received thrice-weekly standard hemodialysis for more than 3 months were recruited. Exclusion Criteria: active systemic disease, liver cirrhosis, malignancy, receiving immunosuppressive treatment, dialysis with temporal non-tunneled catheter, inadequate dialysis dose (kt/V<1.2).

Ages Eligible for Study
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Minimum 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Removal of a wide spectrum of solutes | The primary objective is to compare the removal of a wide spectrum of solutes such as middle and protein-bound molecules | 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intradialytic tolerance | intradialytic tolerance including symptomatic hypotension, cramps, headache, nutrition, and inflammatory status. | 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hemodiafiltration, pre-dilution, post-dilution, uremic toxins