Effect of Varied Dialysate Bicarbonate Levels on Phosphate and Potassium Removal

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Chronic Dialysis Patients

Intervention / Treatment
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* Drug: Bicarbonate hemodialysis solution (low concentration)
* Drug: Bicarbonate hemodialysis solution (high concentration)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum 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
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemodialysis patients<br>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)<br>* One-week experimental session (3 dialysis treatments) with low dialysate bicarbonate (28 mmol/L)<br>Drug: Bicarbonate hemodialysis solution (high concentration)<br>* One-week experimental session with high dialysate bicarbonate (38 mmol/L)<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatrics, phosphate and postassium revmoval, dialysate bicarbonate modeling