Assessment of hemodialysis clinical practices using polyaryl ether sulfone-polyvinylpyrrolidone (PAES: PVP) clinical membrane: Modeling of in vitro fibrinogen adsorption, in situ synchrotron-based imaging, and clinical inflammatory biomarkers investigations

Abstract

Protein adsorption in highly undesirable in hemodialysis (HD) since it leads to activation biochemical cascades and membrane fouling. The present study aims to obtain an in-depth understanding of the influence of clinical practice on in-vitro adsorption of fibrinogen (FB) and inflammatory biomarkers released in patients’ uremic blood during and after HD. A mathematical model to predict human serum FB adsorption to Polyaryl Ether Sulfone-Polyvinylpyrrolidone (PAES: PVP) HD hemodialysis membrane currently used in Canadian hospitals was obtained function of feed flow rate, dialysate flow rate and treatment time. Advanced imaging and spectroscopy techniques were applied to assess the occurrence of FB adsorption. A UV/vis spectroscopic was utilized to measure quantitatively the FB adsorption during simulated HD session. In-situ Synchrotron-based X-ray microtomography (SR-µCT) is an innovative technique and was used in this study to evaluate the in vitro adsorption of conjugated human serum FB in each membrane layer. In-situ SR-µCT showed more severe fouling between intermediate and lower layers of the investigated region. Furthermore, the clinical data was used to correlate the adsorption of FB to inflammatory and thrombotic responses experienced by HD patients. Samples were collected from dialysis patients to ascertain the extent of inflammatory biomarkers released, before, during and after dialysis. 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. The results showed that the hydrodynamic conditions affect both the concentration of FB adsorbed and the time of saturation, and the results presented demonstrate how the clinical operating conditions can be manipulated to control protein adsorption during hemodialysis. In addition, the inflammatory biomarker released during the in vitro incubation of the membrane in uremic blood was compared to the ones released during dialysis at the same duration was compared to examine the influence of hydrodynamics conditions. The clinical study demonstrated how the hydrodynamic conditions influence complement activation, inflammatory and thrombotic responses. Overall, patients treated at lower flow rate demonstrated a more inflammatory profile and stronger tendencies to coagulation and clotting.