Sodium Chloride and Protein-Bound Toxin Removal in Hemodiafiltration

Not Applicable

Completed

Conditions: End-stage Renal Disease

Interventions: Procedure: HDF NaCl
Procedure: Hemodialysis
Procedure: Standard Predilution Hemodiafiltration

Registration Number: NCT01923961

Lead Sponsor: EXcorLab GmbH

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
HDF NaCl, Then HD, Then Standard Pre-HDF	HDF NaCl	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.
HD, Then Standard Pre-HDF, Then HDF NaCl	HDF NaCl	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.
HDF NaCl, Then HD, Then Standard Pre-HDF	Standard Predilution Hemodiafiltration	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.
HDF NaCl, Then HD, Then Standard Pre-HDF	Hemodialysis	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.
HD, Then Standard Pre-HDF, Then HDF NaCl	Hemodialysis	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.
Standard Pre-HDF, Then HDF NaCl, Then HD	Hemodialysis	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.
Standard Pre-HDF, Then HDF NaCl, Then HD	Standard Predilution Hemodiafiltration	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.
Standard Pre-HDF, Then HDF NaCl, Then HD	HDF NaCl	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.
HD, Then Standard Pre-HDF, Then HDF NaCl	Standard Predilution Hemodiafiltration	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.

Primary Outcome Measures

Name	Time	Method
Removal of Para-cresylsulfate	4 hours	Determination of reduction ratio, which is the ratio of a solute concentration in plasma at baseline and at the end of the intervention
Removal of Indoxylsulfate	4 hours	Determination of the reduction ratio, which is the ratio of a solute concentration in plasma at baseline and at the end of the intervention

Secondary Outcome Measures

Name	Time	Method
Plasma Sodium Concentrations	4 hours	Maximum arterial sodium concentrations
Hemocompatibility	4 hours	Maximum free hemoglobin in plasma, which indicates hemolysis. Hemoglobin is released into plasma in case of red blood cell destruction.