End-stage Renal Disease
Conditions
Keywords
Maintenance hemodialysis or hemodiafiltration, >18 years, Stable condition
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.
Interventions
PROCEDUREHDF NaCl
PROCEDUREHemodialysis
PROCEDUREStandard Predilution Hemodiafiltration
Sponsors
EXcorLab GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HDF NaCl, Then HD, Then Standard Pre-HDF Participants first received hemodiafiltration with infusion of 5 M NaCl for 4 hours. After a washout period of 1 week, they then received 4 hours of bicarbonate hemodialysis. After another washout period of 1 week, they reveived 4 hours of standard predilution hemodiafiltration. | 3 |
| HD, Then Standard Pre-HDF, Then HDF NaCl Participants first received bicarbonate hemodialysis for 4 hours. After a washout period of 1 week, they then received 4 hours of standard predilution hemodiafiltration. After another washout period of 1 week, they reveived 4 hours of hemodiafiltration with infusion of 5 M NaCl. | 3 |
| Standard Pre-HDF, Then HDF NaCl, Then HD Participants first received standard predilution hemodiafiltration for 4 hours. After a washout period of 1 week, they then received 4 hours of hemodiafiltration with infusion of 5 M NaCl. After another washout period of 1 week, they reveived 4 hours of bicarbonate hemodialysis. | 2 |
| Total | 8 |
Baseline characteristics
| Characteristic | HD, Then Standard Pre-HDF, Then HDF NaCl | Standard Pre-HDF, Then HDF NaCl, Then HD | Total | HDF NaCl, Then HD, Then Standard Pre-HDF |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 3 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 5 Participants | 2 Participants |
| Age, Continuous | 62 years | 62 years | 62 years | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 8 Participants | 3 Participants |
| Region of Enrollment Germany | 3 participants | 2 participants | 8 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 4 Participants | 1 Participants |
| Sodium Chloride (NaCl) Infusion | 3 Participants | 2 Participants | 8 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
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
Time frame: 4 hours
Population: Per protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hemodiafiltration, NaCl Infusion | Removal of Indoxylsulfate | 34.8 percentage of reduction | Standard Deviation 23.5 |
| Hemodialysis | Removal of Indoxylsulfate | 26.5 percentage of reduction | Standard Deviation 18.1 |
| Hemodiafiltration | Removal of Indoxylsulfate | 30.9 percentage of reduction | Standard Deviation 23.9 |
Primary
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
Time frame: 4 hours
Population: Per protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hemodiafiltration, NaCl Infusion | Removal of Para-cresylsulfate | 42.0 percentage of reduction | Standard Deviation 22.1 |
| Hemodialysis | Removal of Para-cresylsulfate | 32.6 percentage of reduction | Standard Deviation 18.5 |
| Hemodiafiltration | Removal of Para-cresylsulfate | 33.6 percentage of reduction | Standard Deviation 16.1 |
Secondary
Hemocompatibility
Maximum free hemoglobin in plasma, which indicates hemolysis. Hemoglobin is released into plasma in case of red blood cell destruction.
Time frame: 4 hours
Population: Per protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hemodiafiltration, NaCl Infusion | Hemocompatibility | 0.09 percentage of total hemoglobin | Standard Deviation 0.04 |
| Hemodialysis | Hemocompatibility | 0.07 percentage of total hemoglobin | Standard Deviation 0.03 |
| Hemodiafiltration | Hemocompatibility | 0.08 percentage of total hemoglobin | Standard Deviation 0.02 |
Secondary
Plasma Sodium Concentrations
Maximum arterial sodium concentrations
Time frame: 4 hours
Population: Per protocol analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hemodiafiltration, NaCl Infusion | Plasma Sodium Concentrations | 136 mval/l | Standard Deviation 3 |
| Hemodialysis | Plasma Sodium Concentrations | 133 mval/l | Standard Deviation 2 |
| Hemodiafiltration | Plasma Sodium Concentrations | 134 mval/l | Standard Deviation 2 |