A Bifunctional Adsorber Particle for the Removal of Hydrophobic Uremic Toxins from Whole Blood of Renal Failure Patients

Abstract

Hydrophobic uremic toxins accumulate in patients with chronic kidney disease, contributing to a highly increased cardiovascular risk. The clearance of these uremic toxins using current hemodialysis techniques is limited due to their hydrophobicity and their high binding affinity to plasma proteins. Adsorber techniques may be an appropriate alternative to increase hydrophobic uremic toxin removal. We developed an extracorporeal, whole-blood bifunctional adsorber particle consisting of a porous, activated charcoal core with a hydrophilic polyvinylpyrrolidone surface coating. The adsorption capacity was quantified using analytical chromatography after perfusion of the particles with an albumin solution or blood, each containing mixtures of hydrophobic uremic toxins. A time-dependent increase in hydrophobic uremic toxin adsorption was depicted and all toxins showed a high binding affinity to the adsorber particles. Further, the particle showed a sufficient hemocompatibility without significant effects on complement component 5a, thrombin-antithrombin III complex, or thrombocyte concentration in blood in vitro, although leukocyte counts were slightly reduced. In conclusion, the bifunctional adsorber particle with cross-linked polyvinylpyrrolidone coating showed a high adsorption capacity without adverse effects on hemocompatibility in vitro. Thus, it may be an interesting candidate for further in vivo studies with the aim to increase the efficiency of conventional dialysis techniques.

Strategies for optimizing urea removal to enable portable kidney dialysis: A reappraisal

“…Though a critical need for portable dialysis, it must be emphasized that urea removal/degradation to regenerate the dialysate solution is only one of the several challenges that remain to be solved for a safe and reliable portable dialysis device. The removal of non-urea uremic toxins has been addressed using sorbent 83,86,99,106,121 and is still being researched with great interests. 122 Still other challenges include blood access, blood compatibility, infection resistance, miniaturization, and safety monitors, among others.…”

“…With a combined mass of over 23.0 g, these uremic retention solutes will interfere with the urea removal process regardless of the method chosen. Removal of these nonurea uremic retention solutes will likely be achieved through adsorption [80][81][82][83][84][85][86] or new removal schemes such as competitive binding 87 in a dedicated unit.…”

Uremic Toxins Affecting Cardiovascular Calcification: A Systematic Review

“…Applying alternative elimination principles in combination with classical filtration and diffusion technologies might be helpful to achieve a more effective removal of protein-bound uremic toxins in the future. This could include the adsorption of protein-bound uremic toxins [73][74][75][76][77], also in combination with fractionated plasma separation [77]. Furthermore, a high-frequency field could enhance the release of hydrophobic uremic toxins from plasma protein complexes and thereby increase their removal from blood during dialysis (patent numbers: WO2013004604A1, EP2729198A1, US20140246367A1).…”

A critical review of hemoperfusion adsorbents: materials, functionalization and matrix structure selection

“…However, it is clinically inaccessible due to plethora of adverse effects. 97 The commercially packed microsphere columns for hemoperfusion are shown in interaction showed superior mechanical strength, self-anticoagulation capability and robust adsorption capacities for diverse kinds of toxins, owing to the dual-network structure, heparin-mimicking gel structure and strong charge and π-π interactions, respectively. 33 The satisfactory adsorption capability and convenience without extra injection of heparin makes this method a potential strategy for future clinical chronic liver and chronic renal failure treatment.…”