Effect of Varied Dialysate Bicarbonate Levels on Phosphate and Potassium Removal

Effect of Varied Dialysate Bicarbonate Levels on Phosphate and Potassium Removal: A Pilot Study

Modeling of bicarbonate within the dialysate fluid, specifically a lower than standard concentration has been suggested in facilitating the removal of phosphate and potassium. To test this hypothesis, the study will use a cross-over study design to evaluate phosphate and potassium removal during dialysis by altering bicarbonate concentration in dialysis fluid (i.e. high bicarbonate, standard bicarbonate washout, low bicarbonate), and compare the effects of the different dialysate bicarbonate concentrations on the removal of phosphate and potassium during hemodialysis

Study Overview

• Status: Completed
• Conditions: Chronic Dialysis Patients
• Intervention / Treatment: Drug: Bicarbonate hemodialysis solution (low concentration); Drug: Bicarbonate hemodialysis solution (high concentration)

Detailed Description

Elevation of blood phosphate levels in chronic dialysis patients is associated with increased mortality due to cardiovascular events, and if sustained leads to hyperactivity of parathyroid glands and renal bone disease. Similarly, increased calcium-phosphate product as a result of elevated levels of phosphate in the blood is an additional risk factor for vascular calcification. Elevated blood potassium levels is another major electrolyte disorder in patients with advanced renal disease which is potentially life threatening. Therefore control of blood phosphate and potassium levels is a fundamental component of treatment for end stage renal disease. Management of hyperelectrolyte levels in renal failure patients requires restriction of phosphate and potassium intake through dietary measures, promotion of excretion via GI tract through medication delivery (i.e. supplementary binders), and removal through dialysis. All these strategies come with limitations however, specifically adherence to dietary restrictions and medication compliance is poor due to lack of immediate repercussions, as well as the complex kinetics involved with removal via dialysis given the dependence on duration and frequency of dialysis whose manipulation is limited by time considerations for the patient and scheduling issues in the dialysis unit.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients 0-18 years old
• Patients receiving maintenance hemodialysis* for a total of 9-15 hours per week
• Pre-dialysis serum potassium value between 4.0 and 6.5 mmol/L on the first day of the treatment protocol
• Pre-dialysis serum phosphate value greater than low normal for age on the first day of the treatment protocol
• Pre-dialysis serum bicarbonate (total CO2) value between 18 and 30 mmol/L on the first day of the treatment protocol
• Pre-dialysis corrected calcium value between 1.80-2.85 mmol/L on the first day of the treatment protocol

Exclusion Criteria:

• Hemodynamically unstable patients (requiring inotropes or midodrine for support).
• Pre-dialysis potassium value < 4.0 or > 6.5 mmol/L on the first day of the treatment protocol
• Pre-dialysis serum phosphate value less than low normal for age on the first day of the treatment protocol (i.e. hypophosphatemia)
• Pre-dialysis serum bicarbonate (total CO2) value <18 or > 30 mmol/L on the first day of the treatment protocol
• Pre-dialysis corrected calcium <1.8 and >2.85 mmol/L on the first day of the treatment protocol
• Patients mechanically ventilated
• Drugs that could modify internal phosphate and potassium balance such as insulin, bicarbonate injection, hypertonic dextrose solution or mannitol infusion during HD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hemodialysis patients; Each patient will be evaluated during a total of 3.5 weeks correlating to routine dialysis treatment appointments. Each participant will start with low bicarbonate, followed by the washout phase (standard bicarbonate), then high bicarbonate, finishing with the follow up period. Dialysis prescription is standardized for each patient throughout the entire 3.5 week study period.

Drug: Bicarbonate hemodialysis solution (low concentration); One-week experimental session (3 dialysis treatments) with low dialysate bicarbonate (28 mmol/L); Drug: Bicarbonate hemodialysis solution (high concentration); One-week experimental session with high dialysate bicarbonate (38 mmol/L)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phosphate/Potassium Removal	The amount of phosphate/potassium removed with each dialysis as measured from dialysate aliquots and total calculated volume of dialysate. The following formula will be used to calculate Phosphate (PO4) and Potassium (K) mass removal (mmol/treatment): Calculation based on the concentration of K/PO4 (mmol/L) in dialysate x (calculated volume of dialysate + calculated volume of ultrafiltrate)	Dialysis Treatment 1 (Day 1) - Pre and Post dialysis (0hrs and 4hours)
Phosphate/Potassium Removal	The amount of phosphate/potassium removed with each dialysis as measured from dialysate aliquots and total calculated volume of dialysate. The following formula will be used to calculate Phosphate (PO4) and Potassium (K) mass removal (mmol/treatment): Calculation based on the concentration of K/PO4 (mmol/L) in dialysate x (calculated volume of dialysate + calculated volume of ultrafiltrate)	Dialysis Treatment 2 (Day 2) - Pre and Post dialysis (0hrs and 4hours)
Phosphate/Potassium Removal	The amount of phosphate/potassium removed with each dialysis as measured from dialysate aliquots and total calculated volume of dialysate. The following formula will be used to calculate Phosphate (PO4) and Potassium (K) mass removal (mmol/treatment): Calculation based on the concentration of K/PO4 (mmol/L) in dialysate x (calculated volume of dialysate + calculated volume of ultrafiltrate)	Dialysis Treatment 3 (Day 3) - Pre and Post dialysis (0hrs, 4hours, 5hours)
Phosphate/Potassium Removal	The amount of phosphate/potassium removed with each dialysis as measured from dialysate aliquots and total calculated volume of dialysate. The following formula will be used to calculate Phosphate (PO4) and Potassium (K) mass removal (mmol/treatment): Calculation based on the concentration of K/PO4 (mmol/L) in dialysate x (calculated volume of dialysate + calculated volume of ultrafiltrate)	Dialysis Treatment 7 (Day 15) - Pre and Post dialysis (0hrs, 4hours)
Phosphate/Potassium Removal	The amount of phosphate/potassium removed with each dialysis as measured from dialysate aliquots and total calculated volume of dialysate. The following formula will be used to calculate Phosphate (PO4) and Potassium (K) mass removal (mmol/treatment): Calculation based on the concentration of K/PO4 (mmol/L) in dialysate x (calculated volume of dialysate + calculated volume of ultrafiltrate)	Dialysis Treatment 8 (Day 16) - Pre and Post dialysis (0hrs, 4hours)
Phosphate/Potassium Removal	The amount of phosphate/potassium removed with each dialysis as measured from dialysate aliquots and total calculated volume of dialysate. The following formula will be used to calculate Phosphate (PO4) and Potassium (K) mass removal (mmol/treatment): Calculation based on the concentration of K/PO4 (mmol/L) in dialysate x (calculated volume of dialysate + calculated volume of ultrafiltrate)	Dialysis Treatment 9 (Day 17) - Pre and Post dialysis (0hrs, 4hours, 5hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Phosphate Levels	Measurement of the biochemical (serum) parameters of Phosphate for each dialysis treatment	Baseline and Post Dialysis (4hours)
Plasma Potassium Levels	Measurement of the biochemical (serum) parameters of Potassium for each dialysis treatment	Pre and Post Dialysis
Total Plasma CO2 (bicarbonate)	Measurement of the biochemical (serum) parameters of CO2 (bicarbonate) for each dialysis treatment	Pre and Post Dialysis (0 and 4hours)
Corrected Calcium Measurement	Biochemical measurement of the blood for corrected caclium (calcium and albumin) for each dialysis treatment	Pre and Post Dialysis (0 and 4hours)
Dialysis Adequacy (Kt/ V)	Measurement of Blood urea will be performed for each dialysis treatment.	Pre and Post Dialysis (0 and 4hours)
Dialysis Adequacy (Urea Reduction Ratio -URR)	Measurement of Blood urea will be performed for each dialysis treatment.	Pre and Post Dialysis (0 and 4hours)

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Denis Geary, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 23, 2013
• First Submitted That Met QC Criteria: August 23, 2013
• First Posted (Estimate): August 28, 2013

Study Record Updates

• Last Update Posted (Estimate): May 28, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: pediatrics; phosphate and postassium revmoval; dialysate bicarbonate modeling
• Additional Relevant MeSH Terms: Dialysis Solutions; Pharmaceutical Solutions; Hemodialysis Solutions
• Other Study ID Numbers: 1000014657