Evaluation of Two Non-Invasive Extracorporeal Strategies for Enhancing Protein-Bound Uremic Toxin Removal During Hemodialysis.
7 affiliations
- 1Department of Nephrology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.
- 2IMEC the Netherlands-Health Research, 5656 AE Eindhoven, The Netherlands.
- 3European Kidney Health Alliance (EKHA), 1000 Brussels, Belgium.
- 4Department of Medical Technology and Clinical Physics, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.
- 5Division of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.
- 6Aachen-Maastricht Institute for Cardiorenal Disease (AMICARE), University Hospital RWTH Aachen, 52074 Aachen, Germany.
- 7BIOS Lab on a Chip Group, Faculty of EEMCS, University of Twente, 7500 AE Enschede, The Netherlands.
Abstract
Current hemodialysis (HD) methods inefficiently remove protein-bound uremic toxins (PBUTs) due to their high binding affinity to plasma proteins, mainly albumin. This study aimed to investigate electromagnetic (EM) fields and temperature as potential extracorporeal, non-systemic methods to increase HD PBUT clearance. PBUT release was measured in infusible (caprylate-stabilized) albumin solutions spiked with indoxyl sulfate (IS) using an in vitro dialysis setup including a real-time, in-line IS-sensor. No measurable influence on PBUT release was observed during EM field-tests (f = 1-600 MHz, E <= 1 kV/m), but temperature tests (35-40 °C range) showed an absolute increase in IS free fraction of 0.7%/°C. Furthermore, static equilibrium dialysis tests, including IS, p-cresyl sulfate (pCS) and hippuric acid (HA), showed a free fraction increase for all three PBUTs upon a temperature increase from 37 °C to 43 °C (IS 1.30-fold, pCS 1.12-fold, HA 1.15-fold). Mathematical modeling showed a 1.14-fold decrease in plasma IS concentration after 5 weeks of HD, and exploratory hemocompatibility tests did not reveal pronounced changes over 15 heating cycles at 43 °C under static conditions. Extracorporeal temperature elevation is a promising technique to enhance PBUT removal during hemodialysis, which may be easily combined with current HD machines, does not break sterility, and avoids elevating free PBUTs inside the body.
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BibTeX
@article{bras2026evaluation,
title = {{Evaluation of Two Non-Invasive Extracorporeal Strategies for Enhancing Protein-Bound Uremic Toxin Removal During Hemodialysis.}},
author = {João G Brás and Fokko P Wieringa and Babette H Lentferink and Simon Kootwijk and Albert H Westra and Leonard J van Schelven and Mies van Steenbergen and Joachim Jankowski and Marianne C Verhaar and Karin G F Gerritsen and Jeroen C Vollenbroek},
journal = {Toxins},
year = {2026},
month = oct,
doi = {10.3390/toxins18100443},
url = {https://europepmc.org/article/MED/42931534},
note = {CC BY},
}
RIS
TY - JOUR
TI - Evaluation of Two Non-Invasive Extracorporeal Strategies for Enhancing Protein-Bound Uremic Toxin Removal During Hemodialysis.
AU - João G Brás
AU - Fokko P Wieringa
AU - Babette H Lentferink
AU - Simon Kootwijk
AU - Albert H Westra
AU - Leonard J van Schelven
AU - Mies van Steenbergen
AU - Joachim Jankowski
AU - Marianne C Verhaar
AU - Karin G F Gerritsen
AU - Jeroen C Vollenbroek
PY - 2026
DA - 2026/10/13
JO - Toxins
DO - 10.3390/toxins18100443
UR - https://europepmc.org/article/MED/42931534
AB - Current hemodialysis (HD) methods inefficiently remove protein-bound uremic toxins (PBUTs) due to their high binding affinity to plasma proteins, mainly albumin. This study aimed to investigate electromagnetic (EM) fields and temperature as potential extracorporeal, non-systemic methods to increase HD PBUT clearance. PBUT release was measured in infusible (caprylate-stabilized) albumin solutions spiked with indoxyl sulfate (IS) using an in vitro dialysis setup including a real-time, in-line IS-sensor. No measurable influence on PBUT release was observed during EM field-tests (f = 1-600 MHz, E <= 1 kV/m), but temperature tests (35-40 °C range) showed an absolute increase in IS free fraction of 0.7%/°C. Furthermore, static equilibrium dialysis tests, including IS, p-cresyl sulfate (pCS) and hippuric acid (HA), showed a free fraction increase for all three PBUTs upon a temperature increase from 37 °C to 43 °C (IS 1.30-fold, pCS 1.12-fold, HA 1.15-fold). Mathematical modeling showed a 1.14-fold decrease in plasma IS concentration after 5 weeks of HD, and exploratory hemocompatibility tests did not reveal pronounced changes over 15 heating cycles at 43 °C under static conditions. Extracorporeal temperature elevation is a promising technique to enhance PBUT removal during hemodialysis, which may be easily combined with current HD machines, does not break sterility, and avoids elevating free PBUTs inside the body.
SN - 2072-6651
ER -