Biocompatibility assessment of haemodialysis membrane materials by proteomic investigations

Abstract

The exposure of blood to an artificial surface such as the haemodialysis membrane results in the nearly instantaneous deposition of a layer of plasma proteins. The composition of the protein layer profoundly influences all subsequent events, and to a large extent determines the biocompatibility of the biomaterial. In the present study, we examine the protein adsorption capacity and coagulation profiles of the polysulfone-based helixone material in comparison to cellulose triacetate. A differential profiling investigation using shotgun proteomics data-independent analysis was applied to eluates obtained with each membrane after a dialysis session, in order to assess the function of desorbed proteins. Functional classification and network analysis performed using bioinformatics tools shed light on the involvement of adsorbed proteins into important molecular processes, such as lipid transport and metabolism, cell growth differentiation and communication, and the coagulation cascade. The collected evidence was further validated by targeted mass spectrometry using selected reaction monitoring on proteotypic transitions of key protein effectors, confirming the different panels of adsorbed protein on each membrane. The coagulation profile during haemodialysis of patients under polysulfone-based helixone filter cartridges was also assessed showing a slightly higher platelet activation profile after the dialysis session. The overall collected evidence highlights a modulation of the coagulation biological pathway during haemodialysis, which is largely influenced by the biomaterial used.

Assessing the contact‐activation of coagulation during hemodialysis with three different polysulfone filters: A prospective randomized cross‐over trial

“…These Filters (A and C) differ in the surface area and, in a chemical perspective, for the presence in Filter C of some polyamide, which is included to enhance endotoxin retention by the membrane. Recently a proteomic investigation with membranes composed of different materials (cellulose triacetate and Helixone®) shed light on the modulation of the coagulation system and on its dependence on the biomaterial used . In this experimental study, the retention on PSf‐based Helixone® membranes of proteins associated with the coagulation cascade suggests an active role by the membrane in modulating that biological process, in keeping with recent observations of a significant coagulation activation during haemodialysis with PSf‐based materials.…”

Proteomic Characterization of a New asymmetric Cellulose Triacetate Membrane for Hemodialysis

“…ATA filter appears to retain more proteins involved in pathways related to the signaling of clathrin‐mediated endocytosis, atherosclerosis, interleukin‐12 (IL‐12) production by macrophages, and the signaling of nitric oxide and reactive oxygen species production (red dashed line in Figure A). Conversely, CTA filter retains more proteins involved in the canonical pathway of the coagulation system, in the intrinsic and extrinsic prothrombin activation pathways, and in primary immunodeficiency signaling (green dashed line in Figure A), consistent with our previous report …”

“…The levels of some blood biochemical parameters that might possibly vary during HD cycles were first measured for each subject enrolled in this study. It is known that dialysis membranes are able to retain proteins related to the extrinsic coagulation pathways and may have a modulatory effect on several biological functions and mechanisms, as well as that many endogenous chemicals may be removed from the bloodstream during HD treatment. We therefore measured parameters related to the coagulation cascade—namely prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR)—together with circulating levels of vitamin D, cholesterol, and albumin (ALB) before and after HD procedure with ATA or CTA filters.…”

“…Membrane performance can thus be evaluated in terms of removal efficiency and minimization of negative blood/membrane material interactions. Evidence accumulated over the years suggests that each single dialysis membrane has multiple and different characteristics, which affects its clearance and biocompatible properties …”

Efficacy of a Novel Granulocyte Monocyte Apheresis Adsorber Device in the Treatment of Inflammatory Bowel Diseases: A Pilot Study

“…During and after the treatment, all patients (100%, 8) with CD and 80% of patients affected by UC achieved the clinical benefit in terms of the decrease ≥ 30% of disease activity indexes (after the 5 th session of GMA: CDAI score 68.33 ± 24.83, P = 0.0003; Mayo score 5.10 ± 1.44, P = 0.00009), with a sustained improvement which lasted until the 48 th week of the monitoring (CDAI score 71.80 ± 33.09, P = 0.0002; Mayo score 4.13 ± 0.64, P = 0.00005) (Figs ).…”