Targeting Albumin Binding Function as a Therapy Goal in Liver Failure: Development of a Novel Adsorbent for Albumin Dialysis

Abstract

Liver failure results in impaired hepatic detoxification combined with diminished albumin synthesis and is associated with secondary organ failure. The accumulation of liver toxins has shown to saturate albumin binding sites. This was previously demonstrated by an in vitro test for albumin binding capacity (ABiC) that has shown to inversely correlate with the established MELD (Model for End-Stage Liver Disease) score. In this study, we introduced a new adsorbent material for albumin dialysis treatments that improves albumin binding capacity. The new charcoal adsorbent was developed by an evolutionary test schedule. Batch testing of charcoals was performed as steady-state experiments. The charcoal reflecting the highest increase in albumin binding capacity was then introduced to kinetic models: Perfusion tests were designed to evaluate adsorption capacity and kinetics for liver failure marker toxins. A dynamic recirculation model for liver failure was used for upscaling and comparison against conventional MARS adsorbents as the gold standard in an albumin dialysis setting. Batch tests revealed that powdered activated Hepalbin charcoal displayed the highest ABiC score. Hepalbin charcoal also demonstrated higher adsorptive capacity and kinetics for liver failure marker toxins as determined by perfusion tests. These findings translated to tests of upscaled adsorbents in a dynamic model for liver failure: upscaled Hepalbin adsorbent removes bile acids, direct bilirubin and indirect bilirubin significantly better than MARS adsorbents and significantly increases ABiC. The novel adsorbent Hepalbin offers a significant improvement over both MARS adsorbents concerning liver failure marker toxin removal and ABiC improvement.

Similarities, Differences, and Potential Synergies in the Mechanism of Action of Albumin Dialysis Using the MARS Albumin Dialysis Device and the CytoSorb Hemoperfusion Device in the Treatment of Liver Failure

“…The recirculation circuit contains albumin-enriched dialysate (400 mL 20% human serum albumin [HSA] in dialysate solution). Due to known saturation effects of MARS adsorbents diaMARS AC250 and diaMARS IE 250 during MARS treatments [20-23], MARS adsorbents were exchanged with a Hepalbin adsorbent (Hepalbin Cluster 12 ; Albutec GmbH, Rostock, Germany), previously shown to have improved adsorbent capacity [24]. This allows for a comparison of albumin dialysis and hemoperfusion concerning toxin transfer.…”

Extracorporeal albumin dialysis in critically ill patients with liver failure: Comparison of four different devices—A retrospective analysis

“… 3 The cluster incorporates powdered activated Hepalbin charcoal on a cellulose framework combined with a cationic binding polymer. 4 ADVOS uses the aforementioned circuits, incorporated into a separate machine setup, but albumin is regenerated by adding acid and bases. 5 SPAD represent a rapid and easy to setup ECAD system using conventional hemodialysis machines.…”

Functionalization of Poly(styrene-co-methyl methacrylate) Particles for Selective Removal of Bilirubin

“…There have been different approaches used in the development of bilirubin-capturing materials [ 3 , 4 , 5 , 6 , 7 ]. Thus far, materials based on polystyrene, polystyrene-divinylbenzene [ 8 ], anion exchange resins [ 9 ], activated carbon, cellulose matrix combined with cationic binding polymers [ 10 ] and even bile acid inhibitors based on sodium salts [ 11 ], have been described to remove bilirubin. Unfortunately, these systems have generally shown low selectivity and capacity [ 12 ].…”