Comparison Cytokine Clearance Between SLED-f Using High Cut-off Dialyzer and High-flux Dialyzer in Septic AKI Patients

Study Overview
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Brief Summary
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Hypercytokinemia contributes a major role in the pathogenesis and is associated with the high mortality in sepsis-related acute kidney injury(AKI). This pilot randomized controlled trial was conducted in sepsis-related AKI patients to compare the efficacy of cytokine removal including interleukin(IL)-6, IL-8, IL-10, and tumor necrotic factor(TNF)-α by six-hour SLED-f between using HCO dialyzer(HCO-SLED-f) and HF dialyzer(HF-SLED-f).

Detailed Description
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Hypercytokinemia contributes a major role in the pathogenesis and is associated with the high mortality in sepsis-related acute kidney injury(AKI). Reductions of these cytokines have been reported to improve clinical outcomes. Online sustained low-efficiency diafiltration(SLED-f) using traditional high-flux(HF) dialyzer could remove some cytokines. Interestingly, the potential of enhancing cytokine removal by using newly designed high cut-off(HCO) dialyzer that could theoretically remove larger molecular weight solutes has never been studied in SLED-f before.This pilot randomized controlled trial was conducted in sepsis-related AKI patients to compare the efficacy of cytokine removal including interleukin(IL)-6, IL-8, IL-10, and tumor necrotic factor(TNF)-α by six-hour SLED-f between using HCO dialyzer(HCO-SLED-f,n=8) and HF dialyzer(HF-SLED-f,n=8).

Official Title
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Comparison Cytokine Clearance Between Sustained Low-Efficiency Diafiltration (SLED-f) Using High Cut-off Dialyzer and High-flux Dialyzer in Septic AKI Patients

Conditions
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Acute Kidney Injury, Sepsis

Intervention / Treatment
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* Procedure: SLED-f with HCO dialyzer
* Procedure: SLED-f with HF dialyzer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sepsis Acute kidney injury stage 3 Exclusion Criteria: Profound hemodynamic instability with more than one inotropic drug Pregnancy Breast-feeding Delayed receiving antibiotic up to 6 hours after beginning of septic shock.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SLED-f with HCO dialyzer<br>Online sustained low-efficiency diafiltration (online SLED-f) using novel high cut-off dialyzer which had larger pore size than standard high-flux dialyzer was assigned as the new intervention to compare the efficacy of cytokine removals with the control arm. | Procedure: SLED-f with HCO dialyzer<br>* Online SLED-f with high cut-off dialyzers were performed using the Fresenius 5008S hemodiafiltration machines (Fresenius Medical Care, Bad Homburg, Germany). Super-flux, Sureflux 150FH (Nipro Corporation, Osaka, Japan; cellulose triacetate material, pore size 78 A◦, Kuf 66.9 mL/hr/mmHg, surface area 1.5 m2) were used. Dialysis time and blood flow rate were 6 hours and 200 mL/min, respectively. The predilution reinfusion fluid rate and dialysate flow rate were 80 and 220 mL/min, respectively (the total dialysis fluid flow rate was 300 mL/min).<br>|
| Active Comparator: SLED-f with HF dialyzer<br>Online sustained low-efficiency diafiltration (online SLED-f) using standard high-flux dialyzer in septic acute kidney injury patients was assigned as the control group | Procedure: SLED-f with HF dialyzer<br>* Online SLED-f with standard high-flux dialyzers were performed using the same Fresenius 5008S hemodiafiltration machines (Fresenius Medical Care, Bad Homburg, Germany). High-flux ELISIO 150H (Nipro Corporation, Osaka, Japan; polynephron material, pore size 50-60 A◦, Kuf 67 mL/hr/mmHg, surface area 1.5 m2) were used. Dialysis time and blood flow rate were 6 hours and 200 mL/min, respectively. The predilution reinfusion fluid rate and dialysate flow rate were 80 and 220 mL/min, respectively (the total dialysis fluid flow rate was 300 mL/min).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IL-6 Clearance | Simultaneous pre-and post-dialyzer blood samples from arterial and venous sampling ports were collected at 30 minutes after the treatment was started for determination of dialyzer clearances. | At 30 minutes after the treatment was started | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urea percentage of reduction ratio | Blood samples were taken from patients before and at the end of 6-hour in the first online SLED-f session. The percentage of reduction ratio were calculated from the before and ending samples. | At time 0-hour and 6-hour of the study SLED-f session | 
| Beta2-microglobulin percentage of reduction ratio | Blood samples were taken from patients before and at the end of 6-hour in the first online SLED-f session. The percentage of reduction ratio were calculated from the before and ending samples. | At time 0-hour and 6-hour of the study SLED-f session | 
| IL-10 Clearances | Simultaneous pre-and post-dialyzer blood samples from arterial and venous sampling ports were collected at 30 minutes after the treatment was started for determination of dialyzer clearances. | At 30 minutes after the treatment was started | 
| TNF-α Clearances | Simultaneous pre-and post-dialyzer blood samples from arterial and venous sampling ports were collected at 30 minutes after the treatment was started for determination of dialyzer clearances. | At 30 minutes after the treatment was started | 
| Intradialytic hypotension | The hypotensive events were records | During 6 hours of SLED-f session | 
| Albumin loss in spent dialysate | Continuous sampling of spent effluent dialysate and ultrafiltrate were carried out with a collection pump inserted into the effluent outlet line via a special connector for total albumin loss determination | During 6 hours of SLED-f session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sustained low-efficiency diafiltration (SLED-f), high cut-off dialyzer, cytokines