Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy

End-Stage Renal Disease (ESRD) Clinical Trial

— CIPHEMO  

Official title:

Intracellular Phosphate and Adenosine Triphosphate (ATP) Concentration Evolution by Magnetic Resonance (MR) Spectroscopy in Patients During Hemodialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03119818
• Other study ID #: 69HCL17_0047
• Status: Completed
• Phase: N/A
• First received: April 11, 2017
• Last updated: February 23, 2018
• Start date: June 14, 2017
• Est. completion date: July 29, 2017

Study information

• Verified date: April 2017
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

End-stage renal disease is associated with hyperphosphatemia due to a decrease of renal phosphate excretion. This hyperphosphatemia is associated with an increase of cardiovascular risk and mortality. Thus, three therapeutic options have been developed: dietary restriction, administration of phosphate binders and phosphorus clearance by hemodialysis (HD).

During a standard HD session, around 600 to 700mg phosphate is removed from the plasma, whereas it contains only 90 mg inorganic phosphate (Pi); 85% of phosphate is stored in bones and teeth in hydroxyapatite form, 14% is stored in the intracellular space (90% organic phosphate and 10% Pi), and 1% remains in the extracellular space.

Currently, the source of Pi cleared during HD remains to be determined. Phosphorus (31P) magnetic resonance spectroscopy allows reliable, dynamic and non-invasive measurements of phosphate intracellular concentration. The investigator's team recently published data obtained in anephric pigs, suggesting that phosphate intracellular concentration increases during a HD session. In parallel, we showed that ATP intracellular concentration decreased. These results suggest that the source of Pi cleared during HD could be located inside the cell.

In this study, investigators will measure intracellular phosphate and ATP concentrations and intracellular potential of hydrogen (pH) evolution during hemodialysis in 12 patients suffering from end-stage renal disease by MR spectroscopy.

If these results were confirmed in humans, it could explain, at least in part, HD intolerance in some patients and would lead to modify therapeutic approaches of hyperphosphatemia, for example, by modifying HD sessions time.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: July 29, 2017
• Est. primary completion date: July 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patient suffering from end-stage renal disease, treated by chronic hemodialysis since at less 6 months

• Phosphatemia (at the start of the session) = 1,5 mmol/L and = 3 mmol/L

• written consent signed

Exclusion Criteria:

• Major subject protected by law

• Prisoners or subjects who are involuntarily incarcerated

• Denutrition (weight loss = 5 kg in one months/10 kg in 6 months, Body Mass Index (BMI) = 21 kg/m2, albuminemia = 35 g/L)

• Obesity (BMI = 30 kg/m2)

• Phosphatemia at the start of the dialysis < 1,5 mmol/L or > 3 mmol/L

• Secondary hyperparathyroidism with parathormone (PTH) = 1000 pg/mL

• Adynamic osteopathy (PTH = 50 pg/mL)

• Hypoparathyroidism with a history of parathyroidectomy

• Hemoglobin = 100 g/L

• Contraindication to heparin

• Temporary vascular access

• Contraindication to resonance magnetic spectroscopy (pacemaker or insulin pump, metallic valvular prosthesis, valvular prosthesis not compatible with resonance magnetic spectroscopy, dental appliance, intracerebral clip, claustrophobic subject).

• Simultaneous participation to another research protocol

• Patient not affiliated to a social security system

Related Conditions & MeSH terms

• End-Stage Renal Disease (ESRD)
• Kidney Failure, Chronic

Intervention

Device:
• Phosphorus (31P) magnetic resonance spectroscopy
Phosphorus MR spectroscopy realized using a 3-Tesla MR imaging system. A twenty-cm circular surface coil will be set to the 31P resonance frequency and placed over the leg muscle region to obtain spectroscopy acquisitions. 31P MR spectra will be acquired before, during (every 160 seconds), and 30 minutes after dialysis. 31P MR system data will be analyzed using jMRUI Software. Five different peaks will be analyzed: inorganic phosphate, phosphocreatine, a-, ß-, and ?-ATP.

Other:
• Hemodialysis
Hemodialysis realized using a 5008 generator, a portable plant, a FX80 Dialyzer, a dialyzing solution with a standard electrolytes composition. The dialysis generator will be placed outside of the MRI examination room. The dialysis lines will pass through a wave guide to connect patients positioned on the bed of the MRI. A suitably trained nurse will proceed to the cannulation of the fistula, the connection of the catheter, and the monitoring of the clinical tolerance of the session.

Locations

Country	Name	City	State
France	Service de Néphrologie Pavillon P, Hôpital E. Herriot	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in phosphate intracellular concentration	Measurement of phosphate intracellular concentration evolution during a 4 hours hemodialysis (HD) session using phosphorus magnetic resonance spectroscopy.	Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Secondary	Change in ATP intracellular concentration	Measurement of ATP intracellular concentration evolution during a 4 hours HD session using phosphorus magnetic resonance spectroscopy.	Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Secondary	Change in intracellular pH	Measurement of intracellular pH evolution during a 4 hours HD session using phosphorus magnetic resonance spectroscopy. Intracellular pH will be calculated using the Henderson-Hasselbach formula: Ph = 6.75 + log (d-3.27)/(5.69-d), with d being the difference (in parts per million) between inorganic phosphate (Pi) and phosphocreatine (PCr) resonance frequencies.	Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Secondary	Change in phosphatemia	Measurement of intracellular pH evolution during a 4 hours HD session using phosphorus magnetic resonance spectroscopy. Intracellular pH will be calculated using the Henderson-Hasselbach formula: Ph = 6.75 + log (d-3.27)/(5.69-d), with d being the difference (in parts per million) between Pi (inorganic phosphate) and PCr (phosphocreatine) resonance frequencies.	At start of HD, every 15 minutes during first hour of HD, then every hour during HD, at the end of HD and 30 minutes after HD
Secondary	Calcium balance	Calcium balance will be measured using the formula: (Cae - Cab)(Ve - UF)+(Cae * UF), where Cae is the calcium in the ef?uent, Cab is the calcium in the dialysis solution, Ve is the volume of ef?uent, and UF is the ultra?ltration.	At the end of a 4 hours HD session