Abstract
End stage renal disease (ESRD) patients depend on hemodialysis (HD) as a life-sustaining treatment, but HD membrane properties play a critical role in blood activation during HD and can lead to severe patient outcomes. This study reports on a series of investigations on the common clinical HD membranes available in Canadian hospitals to explore the key reasons behind their susceptibility to blood activation and unstable cytokine. Clinical HD membranes composed of cellulose triacetate (CTA) and polyvinylpyrrolidone: polyarylethersulfone (PAES: PVP) were thoroughly characterized in terms of morphology and chemical composition. Membrane-surface interactions with uremic blood samples after HD treatment were probed using Fourier Transform Infra-Red (FTIR) and Raman spectroscopic techniques in order to understand changes in chemistry on membrane fibers. In addition, as part of this innovative study, we utilized Molecular Modeling Docking to examine the interactions of human blood proteins and membrane models to gain an in-depth understanding of functional group types responsible for perceived interactions. In-vitro adsorption of fibrinogen on different clinical HD membranes was compared at similar clinical operating conditions. Samples were collected from dialysis patients to ascertain the extent of inflammatory biomarkers released, before, during (30 and 90 min) and after dialysis (4 h). Collected blood samples were analyzed using Luminex assays for the inflammatory biomarkers of Serpin/Antithrombin-III, Properdin, C5a, 1L-1α, 1L-1β, TNF-α, IL6, and vWF. We have likewise incubated uremic blood in vitro with the two membrane materials to determine the impact that membrane materials pose in favor of activation away from the hydrodynamics influences. The results of our morphological, chemical, spectroscopic, and in vitro incubation analyses indicate that CTA membranes have a smoother surface and higher biocompatibility than PAES: PVP membranes, however, it has smaller pore size distribution, which results in poor clearance of a broad spectrum of uremic toxins. However, the rougher surface and greater hydrophilicity of PAES: PVP membranes increases red blood cell rupture at the membrane surface, which promotes protein adsorption and biochemical cascade reactions. Molecular docking studies indicate sulfone functional groups play an important role in the adsorption of proteins and receptors. PAES: PVP membranes result in slower but greater adsorption of fibrinogen, but are more likely to experience reversible and irreversible fouling as well as backfiltration. Our major finding is that a single dialysis session, even with a more biocompatible membrane such as CTA, increases the levels of complement and inflammation factors, but to a milder extent than dialysis with a PAES membrane.