Intracellular Phosphate and ATP Depletion Measured by Magnetic Resonance Spectroscopy in Patients Receiving Maintenance Hemodialysis

Abstract

Background: The precise origin of phosphate that is removed during hemodialysis remains unclear; only a minority comes from the extracellular space. One possibility is that the remaining phosphate originates from the intracellular compartment, but there have been no available data from direct assessment of intracellular phosphate in patients undergoing hemodialysis.

Methods: We used phosphorus magnetic resonance spectroscopy to quantify intracellular inorganic phosphate (Pi), phosphocreatine (PCr), and βATP. In our pilot, single-center, prospective study, 11 patients with ESKD underwent phosphorus (31P) magnetic resonance spectroscopy examination during a 4-hour hemodialysis treatment. Spectra were acquired every 152 seconds during the hemodialysis session. The primary outcome was a change in the PCr-Pi ratio during the session.

Results: During the first hour of hemodialysis, mean phosphatemia decreased significantly (-41%; P<0.001); thereafter, it decreased more slowly until the end of the session. We found a significant increase in the PCr-Pi ratio (+23%; P=0.001) during dialysis, indicating a reduction in intracellular Pi concentration. The PCr-βATP ratio increased significantly (+31%; P=0.001) over a similar time period, indicating a reduction in βATP. The change of the PCr-βATP ratio was significantly correlated to the change of depurated Pi.

Conclusions: Phosphorus magnetic resonance spectroscopy examination of patients with ESKD during hemodialysis treatment confirmed that depurated Pi originates from the intracellular compartment. This finding raises the possibility that excessive dialytic depuration of phosphate might adversely affect the intracellular availability of high-energy phosphates and ultimately, cellular metabolism. Further studies are needed to investigate the relationship between objective and subjective effects of hemodialysis and decreases of intracellular Pi and βATP content.

Clinical trial registry name and registration number: Intracellular Phosphate Concentration Evolution During Hemodialysis by MR Spectroscopy (CIPHEMO), NCT03119818.

Keywords: cell transfer; chronic hemodialysis; hyperphosphatemia.

Copyright © 2021 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

31P-MRS MR spectrum acquisition from calf's muscle. (A) Axial T1-weighted MRI of the calf muscle showing the localization of the 31P-MRS acquisition from the volume of interest (red box) and (B) the acquired MR spectrum showing the different phosphorus containing compounds (Pi; PCr; and α-, β-, and γATP resonance peaks).

Figure 2.

No hemodynamic instability occurred during HD session. Systolic and diastolic BPs (millimeters of mercury) measured every hour until T240 minutes.

Figure 3.

Decrease of urea during HD session. Urea (millimoles per liter) measured every 15 minutes the first hour and then every hour until T240 minutes.

Figure 4.

Decrease of intracellular Pi regarding decrease of extracellular Pi during a HD session. (A) Cumulative concentration of mean phosphate removal (in millimoles) during the HD session. (B) Phosphatemia level changes over the time. (C) PCr-Pi ratio changes over HD session. Dashed lines note the first hours of treatment when Pi starts to decrease.

Figure 5.

Decrease of ATP during a HD session. (A) PCr-βATP over the time. The rate of PCR-Pi changes during the HD session increased significantly using a mixed effects regression model (+31%, P=0.001). (B) Correlation between changes of the PCr-βATP ratios and the depurated phosphate content using the Spearman test (P=0.002). (C) Correlation between the PCr-βATP ratios and the phosphatemia-depurated Pi using the Spearman test (P=0.01).

Figure 6.

Normalization of the acid base status during HD session. Measurements (mean ± SD) during the HD session of (A) bicarbonates concentration, (B) blood pH, and (C) intracellular pH.