Next Extracorporeal Albumin Detoxification/Dialysis (NxECAD) Based on Purified Albumin Dialysate, but Not MARS, Reverses Leukocyte Dysfunction Due to Cholestasis in Multiorgan Failure

Background: Albumin bound toxins (ABT) contribute to renal, -multiorgan failure, and immune paralysis. On top of providing renal support therapy, one goal of extracorporeal albumin detoxification/dialysis (ECAD) is to remove ABT to accelerate resolution of secondary organ failures. Recent research has revealed that elevated levels of certain bile acids due to cholestasis cause leucocyte dysfunction. The aim of this study was to compare the effect of extracorporeal Albumin Dialysis (ECAD) using MARS and NxECAD employing enhanced efficacy charcoal for dialysate albumin recycling, on patient’s leucocyte function. Methods: In an RCT, subjects with progressive jaundice and/or HE and/or RF and/or PR were treated first with one ECAD (MARS or NxECAD) and afterwards crossed over to the other. Pre-and post-values of markers for ABT, Safety and other clinical parameters were compared. Pre- and post-treatment plasma samples were tested for efficacy of ABT removal by Albumin Binding Functions (ABF) using two different methods (dansylsarcosine binding and dodecanoic acid binding by Electron Spin Resonance-ESR-Spectroscopy), concentrations of Bile Acids and suppressive effects on leucocyte function. Results: The percentage of phagocytotic granulocytes remained unchanged when samples before and after MARS were compared. However, it increased significantly when samples pre-NxECAD were compared to samples post NxECAD. Total Bile Acids were reduced significantly by MARS and NxECAD, the change from baseline (CFBL) during NxECAD was significantly higher than for MARS. In parallel, patient`s Albumin Binding Function increased significantly during NxECAD treatments, but not during MARS. Analysis of granulocyte phagocytosis confirmed a reduction due to the disease which could NOT be reversed by MARS, but significantly recovered during NxECAD. Conclusion: Since ECAD appears to have an efficacy dependent effect on reversing leucocyte dysfunction related to accumulation of albumin bound toxins, further clinical studies should investigate if these laboratory findings translate into a reduction of infection rates, improvement of antibiotic response and ultimately survival in subjects with liver failure on extracorporeal support. Funding: Government Support – Non-U.S.