Dose-Response Relationship of Phloretin Therapy on Water and Glucose Transport during Experimental Peritoneal Dialysis
Björk, Martin ; Martus, Giedre LU
and Öberg, Carl M.
LU
(2025)
In Kidney360
- Abstract
Background Water retention, ultrafiltration insufficiency, and metabolic complications due to abnormally high glucose concentrations are still common problems in patients treated with peritoneal dialysis. Phloretin, a nonselective inhibitor of facilitative glucose transporter channels (GLUT), has shown to improve water transport and lower glucose absorption in experimental peritoneal dialysis. However, the dose-response relationship remains unknown, and we therefore performed a dose-response study to elucidate the pharmacodynamic properties of intra-peritoneal phloretin therapy.Methods:Experimental peritoneal dialysis was performed in fifty healthy Sprague-Dawley rats, using glucose-based dialysis fluid containing five different... (More)
Background Water retention, ultrafiltration insufficiency, and metabolic complications due to abnormally high glucose concentrations are still common problems in patients treated with peritoneal dialysis. Phloretin, a nonselective inhibitor of facilitative glucose transporter channels (GLUT), has shown to improve water transport and lower glucose absorption in experimental peritoneal dialysis. However, the dose-response relationship remains unknown, and we therefore performed a dose-response study to elucidate the pharmacodynamic properties of intra-peritoneal phloretin therapy.Methods:Experimental peritoneal dialysis was performed in fifty healthy Sprague-Dawley rats, using glucose-based dialysis fluid containing five different concentrations of phloretin. We utilized radiolabeled 18F-deoxyglucose (18-FDG) to determine the plasma-to-dialysate transport. The data was then analyzed to determine the dose-response relationship of phloretin according to the Hill-model equation.Results:Intraperitoneal phloretin therapy followed a dose-response relationship where higher concentrations of phloretin lowered the diffusion capacity of 18-FDG and conventional glucose, while enhancing ultrafiltration. Phloretin showed high potency for water removal and diffusion outcomes, requiring low concentrations to achieve substantial effects.Conclusions:Intraperitoneal phloretin therapy followed a distinct dose-response relationship, showing high potency in improving ultrafiltration and reducing glucose absorption in experimental PD. These findings support the therapeutic potential of GLUT-inhibitors like phloretin and support future clinical studies to evaluate efficacy and optimal dosing in patients undergoing PD.
(Less)
- author
- Björk, Martin
; Martus, Giedre
LU
and Öberg, Carl M.
LU
- organization
- publishing date
- 2025
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Kidney360
- article number
- 10.34067/KID.0000000717
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:39847435
- scopus:85216961005
- ISSN
- 2641-7650
- DOI
- 10.34067/KID.0000000717
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: Copyright © 2025 The Author(s).
- id
- c2710a93-3eec-48f8-9aa1-9d32c9be3e64
- date added to LUP
- 2025-04-09 15:26:22
- date last changed
- 2025-07-10 03:00:18
@article{c2710a93-3eec-48f8-9aa1-9d32c9be3e64,
abstract = {{<p>Background Water retention, ultrafiltration insufficiency, and metabolic complications due to abnormally high glucose concentrations are still common problems in patients treated with peritoneal dialysis. Phloretin, a nonselective inhibitor of facilitative glucose transporter channels (GLUT), has shown to improve water transport and lower glucose absorption in experimental peritoneal dialysis. However, the dose-response relationship remains unknown, and we therefore performed a dose-response study to elucidate the pharmacodynamic properties of intra-peritoneal phloretin therapy.Methods:Experimental peritoneal dialysis was performed in fifty healthy Sprague-Dawley rats, using glucose-based dialysis fluid containing five different concentrations of phloretin. We utilized radiolabeled <sup>18</sup>F-deoxyglucose (18-FDG) to determine the plasma-to-dialysate transport. The data was then analyzed to determine the dose-response relationship of phloretin according to the Hill-model equation.Results:Intraperitoneal phloretin therapy followed a dose-response relationship where higher concentrations of phloretin lowered the diffusion capacity of 18-FDG and conventional glucose, while enhancing ultrafiltration. Phloretin showed high potency for water removal and diffusion outcomes, requiring low concentrations to achieve substantial effects.Conclusions:Intraperitoneal phloretin therapy followed a distinct dose-response relationship, showing high potency in improving ultrafiltration and reducing glucose absorption in experimental PD. These findings support the therapeutic potential of GLUT-inhibitors like phloretin and support future clinical studies to evaluate efficacy and optimal dosing in patients undergoing PD.</p>}},
author = {{Björk, Martin and Martus, Giedre and Öberg, Carl M.}},
issn = {{2641-7650}},
language = {{eng}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Kidney360}},
title = {{Dose-Response Relationship of Phloretin Therapy on Water and Glucose Transport during Experimental Peritoneal Dialysis}},
url = {{http://dx.doi.org/10.34067/KID.0000000717}},
doi = {{10.34067/KID.0000000717}},
year = {{2025}},
}