Sodium Chloride and Protein-Bound Toxin Removal in Hemodiafiltration

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

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.

Study Overview

• Status: Completed
• Conditions: End-stage Renal Disease
• Intervention / Treatment: Procedure: HDF NaCl; Procedure: Hemodialysis; Procedure: Standard Predilution 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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Elsenfeld, Bavaria, Germany, 63820
      • Dialysis Center Elsenfeld

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HDF NaCl, Then HD, Then Standard Pre-HDF; 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; Other Names: Hemodialysis; Standard Predilution Hemodiafiltration; Procedure: Hemodialysis; Other Names: Standard Predilution Hemodiafiltration; HDF NaCl; Procedure: Standard Predilution Hemodiafiltration; Other Names: Hemodialysis; HDF NaCl
EXPERIMENTAL: HD, Then Standard Pre-HDF, Then 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.	Procedure: HDF NaCl; Other Names: Hemodialysis; Standard Predilution Hemodiafiltration; Procedure: Hemodialysis; Other Names: Standard Predilution Hemodiafiltration; HDF NaCl; Procedure: Standard Predilution Hemodiafiltration; Other Names: Hemodialysis; HDF NaCl
EXPERIMENTAL: Standard Pre-HDF, Then HDF NaCl, Then HD; 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; Other Names: Hemodialysis; Standard Predilution Hemodiafiltration; Procedure: Hemodialysis; Other Names: Standard Predilution Hemodiafiltration; HDF NaCl; Procedure: Standard Predilution Hemodiafiltration; Other Names: Hemodialysis; HDF NaCl

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: EXcorLab GmbH
• Investigators: Principal Investigator: Detlef H Krieter, MD, Wuerzburg University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2013
• Primary Completion (ACTUAL): March 30, 2015
• Study Completion (ACTUAL): August 10, 2015

Study Registration Dates

• First Submitted: August 10, 2013
• First Submitted That Met QC Criteria: August 14, 2013
• First Posted (ESTIMATE): August 16, 2013

Study Record Updates

• Last Update Posted (ACTUAL): January 16, 2019
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Maintenance hemodialysis or hemodiafiltration; >18 years; Stable condition
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: KSSA0113