Citrate Dialysate in Online Hemodialfiltration

Study Overview
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Brief Summary
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Online hemodiafiltration (Ol-HDF) is increasingly being used for patients on chronic dialysis due to in its superiority compared with standard hemodialysis HDF. In addition to an excellent clearance of small molecules, oL-HDF has more advantages by providing both diffusion and convection modalities for an additional clearance of medium-size molecules. Furthermore, OL-HDF has been associated with not only better hemodynamic tolerance and biocompatibility , but may even include better survival.with reduction of proinflammatory cytokines and proinflammatory circulating cells , as well as with better control of B2MG levels .Ol-HDF is classified into 2 types according to the mode of addition of the substitution fluid: pre-dilution OL-HDF (pre-HDF) and post-dilution OL-HDF (post-HDF); Post-HDF was associated with significantly higher removal rates of β2-MG than HD. Postdilution HDF is the most effective way to maximize molecule clearance .Post-HDF was associated with significantly higher removal rate of α1-MG, and also significantly higher albumin leakage, than HD and pre-HDF. However, blood concentrations can be elevated using HDF, which can cause thrombosis. On the other hand, predilution HDF can resolve this problem but requires about three times more purified water than postdilution HDF and may not elicit maximal clearance.

Detailed Description
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Heparin is the most routinely used anticoagulant in hemodialysis. However, it exposes the patient to the risk of bleeding complications and can induce thrombocytopenia. Furthermore, long-term use of heparin induces biological and clinical complications (osteoporosis, dyslipidemia, hyperkalemia) . Regional citrate anticoagulation is a good alternative to heparin use in hemodialysis for patients with increased bleeding risk , but its implementation in bicarbonate hemodialysis (BHD) is laborious and cumbersome: severe side effects can occur due to citrate metabolism and difficulties in adaptation of calcium infusion into the venous line .Therefore, the use of citrate as a dialysis buffer instead of acetate has proven a safe alternative to acetate-containing bicarbonate dialysis and on-line hemodiafiltration without significant hypocalcemia or clinically important coagulation issues.The aim of the present study is the comparison of the patency of the dialyzer ,the quality of life and blood parameters between pre and potdiltuiotn Ol-HDF with citrate dialysate (CD). No study to date has previously compared the use of citrate dialysate between these two modalities in oL-HDF.

Official Title
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Comparison of Citrate Dialysate in Predilution and Postdilution Online Hemodiafiltration : Effect on Clot Formation and Adequacy of Dialysis in Hemodialysis Patients

Conditions
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Heparin, Hemodiafiltration, Haemodialysis, Citrate Reaction

Intervention / Treatment
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* Procedure: Pre-dilution online hemodiafiltration with citrate dialysate
* Procedure: Post-dilution hemodiafiltration with citrate dialysate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable condition Having been under HD for at least three months he vascular access should have blood flow ≥ 300 mL/min. Exclusion Criteria: no heparin use during HD refusal to participate, intolerance or allergy to citrate concurrent infection poor life expectancy due to metastatic cancer, severe cirrhosis and AIDS. patients vascular access modification, patients affected by chronic liver disease, active neoplastic or inflammatory disease were excluded as well as patients receiving immunosuppressive or anti-inflammatory 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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: One group interrupted times-series design (ITS)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-dilution online hemodiafiltration<br>The study was conducted for a 28-week period in two phases: For the first 12 weeks, all of the patients were subjected to CD with pre-dilution oL-HDF.After enrollment, all patients began a 2-week run-in period with conventional dialysis fluid containing acetate and the lowest dose of unfractionated heparin. The investigator titrated the heparin dose by reducing the dose step by step, 25% in each step, until the final minimal dose was achieved. The experimental study consisted of 3 phases, 4 weeks in each phase, and the phases were separated by 1-week washout periods. The second phase will run after finishing the first phase with the same protocol but with post-dilution online HDF.There will be 2 weeks washout period before starting this phase | Procedure: Pre-dilution online hemodiafiltration with citrate dialysate<br>* After enrollment, all patients began a 2-week run-in period with conventional dialysis fluid containing acetate and the lowest dose of unfractionated heparin. The investigator titrated the heparin dose by reducing the dose step by step, 25% in each step, until the final minimal dose was achieved. The experimental study consisted of 3 phases, 4 weeks in each phase, and the phases were separated by 1-week washout periods. Phase 1 used CD with 50% of the heparin dose of the baseline. Phases 2 and 3 used 25% heparin and no heparin, respectively. New dialyzers were introduced at the beginning of each phase and the heparin dose was resumed during the washout phase. The calcium concentration in the dialysis fluid was kept constant (1.5 mmol/L) to allow evaluation of the effect of CD on calcium balance<br>Procedure: Post-dilution hemodiafiltration with citrate dialysate<br>* same protocol with post-dilution Ol-HDF in these same patients for the later 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clotting score between pre and post dilution online-hemodiafiltration | 5 grades of clotting score, Grade 1;No or very little residual blood in the filters.Grade 1;Residual blood in less than 10% of the fibers. Grade 2; Residual blood 10-25%. Grade 3; Residual blood 25-50%.Grade 4 ,Residual blood > 50% | 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life between pre and post dilution online-hemodiafiltration | KDQOL-sf score;0-100.Higher scores reflect better quality of life | 28 weeks | 
| adequacy of dialysis between pre and post dilution online-hemodiafiltration | Kt/V | 28 weeks | 
| calcium level between pre and post dilution online-hemodiafiltration | serum calcium predialysis in midweek of each phase | 28 weeks | 
| phosphorus level between pre and post dilution online-hemodiafiltration | serum calcium predialysis in midweek of each phase | 28 weeks | 
| intact parathyroid level between pre and post dilution online-hemodiafiltration | serum parathyroid level in midweek of each phase | 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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online hemodialfiltration, hemodialysis, citrate, adequacy of dialysis, heparin