Clinical trial NCT03119818: Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy
Official title: Intracellular Phosphate and Adenosine Triphosphate (ATP) Concentration Evolution by Magnetic Resonance (MR) Spectroscopy in Patients During Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End-Stage Renal Disease (ESRD)
Keywords: ESRD
hemodialysis
phosphate
ATP
magnetic resonance spectroscopy
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2017-04-19
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in phosphate intracellular concentration
timeFrame: Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
Secondary outcomes:
measure: Change in ATP intracellular concentration
timeFrame: Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
measure: Change in intracellular pH
timeFrame: Baseline, at start of HD, every 160 seconds during HD, at the end of HD and 30 minutes after HD
measure: Change in phosphatemia
timeFrame: 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
measure: Calcium balance
timeFrame: At the end of a 4 hours HD session
Other outcomes:
Locations:
city: Lyon
country: France
facility: Service de Néphrologie Pavillon P, Hôpital E. Herriot
Study officials:
affiliation: Hospices Civils de Lyon
name: Laurent JUILLARD, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chazot G, Lemoine S, Kocevar G, Kalbacher E, Sappey-Marinier D, Rouviere O, Juillard L. Intracellular Phosphate and ATP Depletion Measured by Magnetic Resonance Spectroscopy in Patients Receiving Maintenance Hemodialysis. J Am Soc Nephrol. 2021 Jan;32(1):229-237. doi: 10.1681/ASN.2020050716. Epub 2020 Oct 22.