Abstract
The number of patients with chronic kidney disease increases while the number of available donor organs stays at approximately the same level. Unavoidable accumulation of the uremic toxins and cytokines for these patients comes as the result of malfunctioning kidneys and their high levels in the blood result in high morbidity and mortality. Unfortunately, the existing methods, like hemodialysis and hemofiltration, provide only partial removal of uremic toxins and/or cytokines from patients’ blood. Consequently, there is an increasing need for the development of the extracorporeal treatments which will enable removal of broad spectrum of uremic toxins that are usually removed by healthy kidneys. Therefore, in this work we developed and tested ordered mesoporous carbons as new sorbents with dual porosity (micro/meso) that provide selective and efficient removal of a broad range of uremic toxins from human plasma. The new sorbents, CMK-3 are developed by nanocasting methods and have two distinct pore domains, i.e. micropores and mesopores, therefore show high adsorption capacity towards small water soluble toxins (creatinine), protein-bound molecules (indoxyl sulfate and hippuric acid), middle molecules (β-2-microglobulin) and cytokines of different size (IL-6 and IL-8). Our results show that small amounts of CMK-3 could provide selective and complete blood purification.
Highlights
Example, clinically relevant blood purification methods like Adsorbents Recirculation System (MARS, Gambro), Prometheus System (Fresenius Medical Care) and Coupled Plasma Plasma Filtration and Adsorption (Bellco) successfully use both adsorption and membrane-based techniques to remove the toxins from patients[3]
Recently our laboratory successfully combined the benefits of adsorption and diffusion in one membrane, the mixed matrix membrane (MMM), which consists of two layers: a selective inner layer which is responsible for blood contact and selectivity and an outer layer where adsorptive particles are incorporated in a highly porous membrane matrix[4,5]
For the proof of concept here, we investigated the removal of a broad range of toxins from human plasma by CMK-3 type adsorbent, including small water soluble molecules, like creatinine (113 Da), middle molecules, like β2m (11.6 kDa), and PBTs like hippuric acid (179 Da, 48% bound to HSA) and indoxyl sulfate (213 Da, 98% bound to HSA), as well as the removal of two cytokines, IL-6 and IL-8 (24 kDa and 8 kDa respectively)
Summary
Example, clinically relevant blood purification methods like Adsorbents Recirculation System (MARS, Gambro), Prometheus System (Fresenius Medical Care) and Coupled Plasma Plasma Filtration and Adsorption (Bellco) successfully use both adsorption and membrane-based techniques to remove the toxins from patients[3]. Due to the carbon precursor pyrolysis process these rods are microporous (0.8–1 nm), and are responsible for the efficient adsorption of small water soluble molecules and PBTs. The space between the rods creates the well-defined and tuneable mesoporous system (5 nm in our case) that should achieve the removal of middle molecules and cytokines without blocking the micropores. For the proof of concept here, we investigated the removal of a broad range of toxins from human plasma by CMK-3 type adsorbent, including small water soluble molecules, like creatinine (113 Da), middle molecules, like β2m (11.6 kDa), and PBTs like hippuric acid (179 Da, 48% bound to HSA) and indoxyl sulfate (213 Da, 98% bound to HSA), as well as the removal of two cytokines, IL-6 and IL-8 (24 kDa and 8 kDa respectively). Norit A Supra was previously used by our laboratory in MMM and showed good ability to remove creatinine and PBTs from human plasma, while Takeda was used practically as a negative control
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