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Smart module for removal of protein bound uremic toxins for artificial kidneys
Jeroen Vollenbroek, Fokko Wieringa, Karin Gerritsen, Joachim Jankowski, Lucas Lindeboom, Rosalinde Masereeuw, Leonard van Schelven
Session: Poster Session 1 (Even numbers)
Session starts: Thursday 26 January, 16:00
Presentation starts: 16:00



Jeroen Vollenbroek (UMC Utrecht Department of Nephrology and Hypertension)
Fokko Wieringa (IMEC Eindhoven, Eindhoven, the Netherlands)
Karin Gerritsen (UMC Utrecht Department of Nephrology and Hypertension)
Joachim Jankowski (Institute for Molecular Cardiovascular Research & AMICARE Institute, RWTH Aachen)
Lucas Lindeboom (IMEC Eindhoven, Eindhoven, the Netherlands)
Rosalinde Masereeuw (Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University)
Leonard van Schelven (UMC Utrecht department of Medical Technology and Clinical Physics )


Abstract:
Most End Stage Kidney Disease (ESKD) patients rely on hemodialysis to remove toxins from their blood. During hemodialysis, toxins smaller than 20-45 kDa are filtered out of the bloodstream into the dialysate. Some small toxins, the Protein Bound Uremic Toxins (PBUTs), are difficult to remove since they are bound to large proteins (e.g. albumin ~66 kDa) [1]. Whereas healthy kidneys can actively and very efficiently secrete these PBUTs, hemodialysis only removes the unbound fraction [2]. PBUTs-accumulation is implicated with injury to the heart, blood vessels, brain and nerves. Simply increasing filter pore size is not an option since the binding blood proteins are vital and should not be removed [1]. The Multi-compatible Implantable Toxin Removal Augmentation Module (MI-TRAM) may greatly enhance PBUT-removal by loosening PBUTs from blood proteins, thereby increasing the free fraction that will be filtered out. A consortium from RWTH Aachen, UMC Utrecht, Utrecht University and IMEC is working on this. High strength, high frequency electromagnetic (EM) fields will be used to shake the electrostatic bonds between blood proteins and PBUTs [3-5]. In vitro experiments by prof. Jankowski, already demonstrated significantly improved PBUT removal using bulky equipment [3]. The MI-TRAM chip, developed by IMEC, is a miniaturized version of this system, compatible with wearable, portable or implantable artificial kidney systems. The chip integrates sensors to monitor hematocrit level, total body water and body temperature. We have built a setup with in-tube stainless steel connectors applying the EM fields across the dialysis membrane and are developing an electrical model for the response and behaviour of the system. In the near future, we will perform in vitro dialysis experiments with the MI-TRAM chip for performance testing, calibration, optimization of field strength and frequencies. Both conventional and novel dialysis membranes will be tested for PBUT removal efficiency enhancement. After successful in vitro testing, we will proceed with in vivo efficacy and safety experiments in a uremic large animal model [6], followed by clinical trials. MI-TRAM has the potential for a rapid clinical introduction of this technology to the benefit of ESKD patients. References: [1] Vanholder R, et al., Toxins 2018, 10, 33. https://doi.org/10.3390/toxins10010033 [2] Masereeuw R, et al., Semin Nephrol. 2014 Mar;34(2):191-208. [3] Patent US2014246367(A1): Jankowski J, et al., Priority year 2011. [4] Patent WO2014095072(A1): Tschulena U, et al., Priority year 2012. [5] Patent EA201500722(A1): Jankowski J, et al., Priority year 2013. [6] Van Gelder et al, Biology 2021, 10, 292. https://doi.org/10.3390/biology10040292