Case studies of clinical hemodialysis membranes: influences of membrane morphology and biocompatibility on uremic blood-membrane interactions and inflammatory biomarkers

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.

Effects of mussel‐inspired co‐deposition of 2‐hydroxymethyl methacrylate and poly (2‐methoxyethyl acrylate) on the hydrophilicity and binding tendency of common hemodialysis membranes: Molecular dynamics simulations and molecular docking studies

“…34 Our research group recently reported a series of investigations on the common clinical HD membranes available in Canadian hospitals (PAES and CTA) to explore the key reasons behind their susceptibility to blood activation and unstable cytokines. [35][36][37] We also reported the improved biocompatibility of PES clinical HD membranes modified with novel ZW copolymers. 29 We also reported how undesired reactions are related to the bio-incompatibility of dialysis membranes and summarized recent advances in hemocompatibility and guidelines for future HD membrane development.…”

“…The binding interactions of the human serum proteins to the membrane is the initial step of the membrane fouling in the hemodialysis process which leads to performance loss. 35,46,47 Accordingly, binding tendency reflects the initial step of fouling and activation of proteins when the HD process starts. concentration of such compounds in the blood, in the case of hypertension as a common side effect of hemodialysis).…”

Hemodialysis-Related Complement and Contact Pathway Activation and Cardiovascular Risk: A Narrative Review

“…Consequently, the CTA membranes resulted in poorer clearance of uremic toxins, but exhibited lower fibrinogen adsorption and caused a less severe increase in complement and inflammatory factors. 51 Studies have also compared the biocompatibility of different types of polysulfone dialyzers. 50 , 52 A study by Koga et al 52 showed that 5 different polysulfone hemodialysis membranes caused different levels of cell activation, fibrin absorption, and oxidative stress, with NV-U membranes proving to be the most biocompatible.…”

Evaluating Fertilizer-Drawn Forward Osmosis Performance in Treating Anaerobic Palm Oil Mill Effluent

“…For the active layer of the CTA membrane, the major spectral feature was the band around 1733 cm −1 that corresponds to the ester carbonyl group (C=O ester), and other characteristic peaks around 1042 and 1230 cm −1 can be assigned to asymmetric and symmetric stretching of C–O bonds [ 43 , 44 ]. The small shoulder around 2960 cm −1 accounted for the C–H bonds [ 45 ]. Figure 15 b compares the AL surface of the CTA membrane for pristine, fouled, and cleaned membranes.…”