Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy

Not Applicable

Completed

• Conditions: End-Stage Renal Disease (ESRD)
• Interventions: Device: Phosphorus (31P) magnetic resonance spectroscopy; Other: Hemodialysis

• Registration Number: NCT03119818
• Lead Sponsor: Hospices Civils de Lyon

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2017-04
• Study First Submitted: 2017-04-11
• Study First Submitted QC: 2017-04-18
• Study First Posted: 2017-04-19
• Study Start: 2017-06-14
• Primary Completion: 2017-07-29
• Study Completion: 2017-07-29
• Last Update Submitted: 2018-02-23
• Last Update Posted: 2018-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients suffering from ESRD treated by chronic hemodialysis	Phosphorus (31P) magnetic resonance spectroscopy	Patients aged from 18 to 80 years old, suffering from ESRD, treated by chronic hemodialysis since at least 6 months and whose phosphatemia at the beginning of HD sessions ranged from 1.5 to 3 mmol/L. Phosphorus (31P) magnetic resonance spectroscopy will be performed in these patients during hemodialysis in order to measure intracellular phosphate and ATP concentrations and intracellular pH evolution during hemodialysis.
Patients suffering from ESRD treated by chronic hemodialysis	Hemodialysis	Patients aged from 18 to 80 years old, suffering from ESRD, treated by chronic hemodialysis since at least 6 months and whose phosphatemia at the beginning of HD sessions ranged from 1.5 to 3 mmol/L. Phosphorus (31P) magnetic resonance spectroscopy will be performed in these patients during hemodialysis in order to measure intracellular phosphate and ATP concentrations and intracellular pH evolution during hemodialysis.

Primary Outcome Measures

Name	Time	Method
Change in phosphate intracellular concentration	Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD	Measurement of phosphate intracellular concentration evolution during a 4 hours hemodialysis (HD) session using phosphorus magnetic resonance spectroscopy.

Secondary Outcome Measures

Name	Time	Method
Change in ATP intracellular concentration	Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD	Measurement of ATP intracellular concentration evolution during a 4 hours HD session using phosphorus magnetic resonance spectroscopy.
Change in intracellular pH	Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD	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 (δ-3.27)/(5.69-δ), with δ being the difference (in parts per million) between inorganic phosphate (Pi) and phosphocreatine (PCr) resonance frequencies.
Change in phosphatemia	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	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 (δ-3.27)/(5.69-δ), with δ being the difference (in parts per million) between Pi (inorganic phosphate) and PCr (phosphocreatine) resonance frequencies.
Calcium balance	At the end of a 4 hours HD session	Calcium balance will be measured using the formula: (Cae - Cab)(Ve - UF)+(Cae \* UF), where Cae is the calcium in the effluent, Cab is the calcium in the dialysis solution, Ve is the volume of effluent, and UF is the ultrafiltration.

Trial Locations

Locations (1)

Service de Néphrologie Pavillon P, Hôpital E. Herriot; 🇫🇷 Lyon, France