Sodium Chloride and Protein-Bound Toxin Removal in Hemodiafiltration

Study Overview
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Brief Summary
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An increase of the free fraction may allow a better removal of of protein-bound uremic toxins during dialysis. During predilution hemodiafiltration, the sodium chloride (NaCl) concentration will be increased in the infusion fluid at a target NaCl concentration and the effect on the removal of protein-bound toxins will be determined. Comparisons will be made to standard hemodialysis and hemodiafiltration.

Detailed Description
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Eight maintenance dialysis patients will be enrolled in a prospective, randomized, crossover trial. HD will be compared with online pre-dilution HDF and HDF at increased plasma ionic strength. The ionic strength will be increased using an infusion fluid with hypertonic [Na+] by isovolumetric adding of a 5000 mmol/L NaCl solution. Blood and dialysate flowrates (250 and 575 mL/min, respectively), treatment time (240 min), and high-flux dialyser (surface area 2.1 sqm, PUREMA H) will be always kept identical. Anticoagulation with standard or fractionated heparin will be unchanged adopted from the patients' routinely used regimen. In both HDF modes, the infusion flow rate will be 125 mL/min. In HDF at increased plasma ionic strength, the infusate [Na+] will be adjusted to approach 240 mmol/L in plasma entering the dialyser and the dialysate [Na+] will be set at the technically feasible minimum of 130 mmol/L. Blood samples will be drawn from the arterial and venous blood lines and, if applicable, from the blood tubing connecting the two dialyzers at 0, 15, 30, 60, 120, 180, and 240 min. Samples at 240 min will be drawn after reducing the blood flow rate to 50 mL/min for 30 s and the dialysate flow turned off. A fraction of the spent dialysate will be continuously collected. Removal of the free and total fraction of para-cresyl sulfate and indoxyl sulfate will be determined by reduction ratios, dialytic clearances and mass in dialysate Hemocompatibility will be assessed by WBC and platelet counts, free Hb, LDH, C5a and TAT. [Na+] will be monitored in both arterial (i.e. before NaCl infusion) and venous blood of the extracorporeal system.

Official Title
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Impact of an Increased Sodium Chloride Concentration in the Infusion Fluid of Predilution Hemodiafiltration on the Removal of Protein-Bound Uremic Toxins

Conditions
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End-stage Renal Disease

Intervention / Treatment
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* Procedure: HDF NaCl
* Procedure: Hemodialysis
* Procedure: Standard Predilution Hemodiafiltration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: End-stage renal disease Maintenance hemodialysis or hemodiafiltration for more than 3 months Stable clinical condition > 18 years Exclusion Criteria: Life expectancy less than 1 year Pregnancy Active infectious disease

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HDF NaCl, Then HD, Then Standard Pre-HDF<br>Participants first receive hemodiafiltration with infusion of 5 M NaCl for 4 hours. After a washout period of 1 week, they then receive 4 hours of bicarbonate hemodialysis. After another washout period of 1 week, they reveive 4 hours of standard predilution hemodiafiltration. | Procedure: HDF NaCl<br> <br> * Other names: Standard Predilution Hemodiafiltration;Procedure: Hemodialysis<br> <br> * Other names: HDF NaCl;Procedure: Standard Predilution Hemodiafiltration<br> <br> * Other names: Hemodialysis;|
| Experimental: HD, Then Standard Pre-HDF, Then HDF NaCl<br>Participants first receive bicarbonate hemodialysis for 4 hours. After a washout period of 1 week, they then receive 4 hours of standard predilution hemodiafiltration. After another washout period of 1 week, they reveive 4 hours of hemodiafiltration with infusion of 5 M NaCl. | Procedure: HDF NaCl<br> <br> * Other names: Standard Predilution Hemodiafiltration;Procedure: Hemodialysis<br> <br> * Other names: HDF NaCl;Procedure: Standard Predilution Hemodiafiltration<br> <br> * Other names: Hemodialysis;|
| Experimental: Standard Pre-HDF, Then HDF NaCl, Then HD<br>Participants first receive standard predilution hemodiafiltration for 4 hours. After a washout period of 1 week, they then receive hemodiafiltration with infusion of 5 M NaCl 4 hours of. After another washout period of 1 week, they reveive 4 hours of bicarbonate hemodialysis. | Procedure: HDF NaCl<br> <br> * Other names: Standard Predilution Hemodiafiltration;Procedure: Hemodialysis<br> <br> * Other names: HDF NaCl;Procedure: Standard Predilution Hemodiafiltration<br> <br> * Other names: Hemodialysis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Removal of Para-cresylsulfate | Determination of reduction ratio, which is the ratio of a solute concentration in plasma at baseline and at the end of the intervention | 4 hours | 
| Removal of Indoxylsulfate | Determination of the reduction ratio, which is the ratio of a solute concentration in plasma at baseline and at the end of the intervention | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Sodium Concentrations | Maximum arterial sodium concentrations | 4 hours | 
| Hemocompatibility | Maximum free hemoglobin in plasma, which indicates hemolysis. Hemoglobin is released into plasma in case of red blood cell destruction. | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Maintenance hemodialysis or hemodiafiltration, >18 years, Stable condition