Biocompatibility Of Hemodialysis Membranes Research Articles

Green synthesized nano-cellulose polyethylene imine-based biological membrane

In hemodialysis process, membrane serves as a barrier between blood and the dialysate. The barrier when contacted by blood accompanied activation of coagulation, immunity, and cellular passageways. In the recent years, hemodialysis membrane's biocompatibility has become a issue which leads to reduce the performance during the separation process. In previous work, we developed and evaluated a cellulose-based membrane blended with polyaziridine or polyetyleneimine in formic acid for hydrophilicity, pure water flux, surface morphology, and permeation efficiency. Biocompatibility was accessed, by conducting cellular viability and cellular attachments tests. In this study, the membrane compared to a non-treated control, and cell viability revealed active and growing cell cultures after 14 days. During the cellular attachment experiment, cell cultures attached to the fabricated membrane simulated the formation of cell junctions, proving that the membrane is non-toxic and biocompatible. CA + PEI + FA membrane tested with a blood mimic fluid having density identical to renal patient's blood. The BSA concentration in the feed solution was the same as that in the blood of the renal patient. The results revealed that the CA + PEI + FA membrane was able to reject 99% bovine serum albumin (BSA) and 69.6% urea. Therefore, from biocompatibility and blood mimic fluid testing, it is confirmed that the CA + PEI + FA membrane is the finest implant for dialysis applications.

A critical review of recent advances in hemodialysis membranes hemocompatibility and guidelines for future development

Hemodialysis is a life-sustaining procedure for patients with end-stage renal disease (ESRD). The efficiency of hemodialysis is limited by the dialysis membrane biocompatibility and the poor clearance of middle-molecule uremic toxins. As a result, hemodialysis is associated with acute chronic side-effects that threaten patients' lives. During hemodialysis, interfacial interactions of blood-polymeric membranes result in several consequences. These interactions lead to the body's various system activations, including the coagulation of blood components, leukocytes (i.e., immune system activation) and complement activations, thrombogenesis, cytokine production, and appearance of radicals with free oxygen. Despite advances in research, the most vital issue in dialysis therapies is the biocompatibility and hemoincompatibility of the membranes. The process of enhancing membrane hemocompatibility is currently posing a global challenge. Reactions to incompatibility can cause severe injuries to the patients and result in morbidity and mortality. This critical review offers a focused analysis of the latest efforts to enhance the hemodialysis membrane's hemocompatibility as well as emphasize current research gaps. Recent innovations (since 2014) in hemodialysis membranes are analyzed in correlation to categories of modified polymer structure chemistry tuning, and surface modifications and their influences on membrane hemocompatibility. Particular attention is paid to: (1) chemical immobilization of functional groups (surface grafting); (2) layer-by-layer chemical attachment of species (LBL); (3) covalent attachment of super hydrophilic-hydrogel; (4) mixed matrix membranes (MMM); and (5) base polymer membrane modification (blending method). This critical review provides an overview of the effects the modification methods can have on biocompatibility and how they can pave the way for optimum enhancement of hemodialysis membrane biocompatibility.

Biocompatibility of Polysulfone Hemodialysis Membranes and Its Mechanisms: Involvement of Fibrinogen and Its Integrin Receptors in Activation of Platelets and Neutrophils.

Activation of blood cells during hemodialysis is considered to be a significant determinant of biocompatibility of the hemodialysis membrane because it may affect patient health adversely through microvascular inflammation and oxidative stress. This study found very different cell activation among various polysulfone (PSf) hemodialysis membranes. For example, CX‐U, a conventional PSf membrane, induced marked adhesion of platelets to its surface and increased surface expression of activated CD11b and production of reactive oxygen species (ROS) by neutrophils; while NV‐U, a hydrophilic polymer‐immobilized PSf membrane, caused little platelet adhesion and slight CD11b expression and ROS production by neutrophils. Analysis of the molecular mechanisms of the above phenomena on CX‐U and NV‐U indicated that anti‐integrin GPIIb/IIIa antibody blocked platelet adhesion, and that the combination of anti‐CD11b (integrin α subunit of Mac‐1) and anti‐integrin αvβ3 antibodies blocked ROS production by neutrophils. Plasma‐derived fibrinogen, a major ligand of GPIIb/IIIa, Mac‐1, and αvβ3 on membranes, was thus analyzed and found to be more adsorbed to CX‐U than to NV‐U. Moreover, comparison between five PSf membranes showed that the number of adherent platelets and neutrophil ROS production increased with increasing fibrinogen adsorption. These results suggested that fibrinogen, adsorbed on membranes, induced GPIIb/IIIa‐mediated platelet activation and Mac‐1/αvβ3‐mediated neutrophil activation, depending on the amount of adsorption. In conclusion, the use of biocompatible membranes like NV‐U, which show lower adsorption of fibrinogen, is expected to reduce hemodialysis‐induced inflammation and oxidative stress by minimizing cell activation.

Reuse and Biocompatibility of Hemodialysis Membranes: Clinically Relevant?

The practice of reprocessing dialyzers for reuse, once predominant in the United States, has been steadily declining over the last 20 years. The professed roles of reuse in improving dialyzer membrane biocompatibility and lowering the risk of first-use syndrome have lost relevance with the advent of biocompatible dialyzer membranes and favorable sterilization techniques. The potential for cost-savings from reuse is also called into question by the easy availability of comparatively cheaper dialyzers and rising regulatory demands and operational cost of reprocessing systems. While the environmental concerns from additional dialyzer-related solid waste from rising single-use practice remains pertinent and requires development of safer dialyzer disposable system technologies, there is no meaningful medical rationale for the continued practice of dialyzer reuse in the twenty-first century.

Thrombocytopenia Associated With One Type of Polysulfone Hemodialysis Membrane: A Report of 5 Cases

Much progress has been made in the biocompatibility of hemodialysis membranes with the development of synthetic membranes. However, despite better biocompatibility, thrombocytopenia has been observed in patients who are dialyzed with various polysulfone membranes. Recent publications have attributed this phenomenon to the electron-beam sterilization of dialyzers. We report 5 cases of thrombocytopenia in patients treated by hemodialysis with an electron-beam sterilized polysulfone membrane. The thrombocytopenia resolved after switching to either of 2 polysulfone membranes, one of which also was electron-beam sterilized. Although we were unable to elucidate the exact biochemical mechanism, the cause of the thrombocytopenia in this series appears to be related to the type of polysulfone and not due to the sterilization technique.

The future of hemodialysis membranes

Hemodialytic treatment of patients with either acute or chronic renal failure has had a dramatic impact on the mortality rates of these patients. Unfortunately, this membrane-based therapy is still incomplete renal replacement, as the mortality and morbidity of these patients remain unacceptably high. Much progress must be made to improve the biocompatibility of hemodialysis membranes as well as their hydraulic and permselective properties to remove small solutes and 'middle molecules' in compact cartridges. The next directions of development will leverage materials and mechanical engineering technology, including microfluidics and nanofabrication, to further improve the clearance functions of the kidney to replicate glomerular permselectivity while retaining high rates of hydraulic permeability. The extension of membrane technology to biohybrid devices utilizing progenitor/stem cells will be another substantive advance for renal replacement therapy. The ability to not only replace solute and water clearance but also active reabsorptive transport and metabolic activity will add additional benefit to the therapy of patients suffering from renal failure. This area of translational research is rich in creative opportunities to improve the unmet medical needs of patients with either chronic or acute renal failure.

Platelet activation through interaction with hemodialysis membranes induces neutrophils to produce reactive oxygen species

The intradialytic activation of leukocytes is one of the major causes of hemodialysis-associated complications. During hemodialysis, the formation of microaggregates consisting of platelets and neutrophils has been observed to accompany the production of reactive oxygen species (ROS) by leukocytes. In this study, we investigated the interaction of platelets and neutrophils with hemodialysis membranes in vitro to elucidate the mechanism underlying microaggregate formation and its relevance to leukocyte activation. The production of ROS in neutrophils was induced by the coincubation of neutrophils with polysulfone (PS) membranes, and was increased when platelets were present in the neutrophil suspension. Neutrophils that were incubated with polymethylmethacrylate (PMMA) membranes in the presence of platelets also produced significant levels of ROS, suggesting that the presence of platelets augmented ROS production in neutrophils. Platelets adhered more firmly to hydrophobic membranes such as PS and PMMA membranes than to hydrophilic membranes, such as those composed of regenerated cellulose (RC) or ethylene vinylalcohol copolymer (EVAL). The adhesion of platelets to dialysis membranes composed of different materials was correlated with those membranes' ability to induce platelet activation as assessed by the cell surface expression of P-selectin. Moreover, coincubation of neutrophils with platelets that had been treated with hydrophobic membranes induced a higher level of superoxide anion relative to those treated with hydrophilic membranes in association with the P-selectin-mediated microaggregate formation. These results suggest that platelets activated through interaction with hemodialysis membranes stimulate neutrophils to produce ROS via P-selectin-mediated adhesion, and that this property of adhesion to platelets is critical for the biocompatibility of hemodialysis membranes.

The AN69 Hemofiltration Membrane Has a Decreasing Effect on the Intracellular Diadenosine Pentaphosphate Concentration of Platelets

Background/Aim: The biocompatibility of hemodialysis membranes has a substantial impact on the mortality of patients with end-stage renal failure. In the present study, the effects of hemodialysis on the intracellular amount of diadenosine pentaphosphate (Ap₅A), a hydrophilic, anionic substance with a low molecular weight, was investigated. Methods: The intracellular Ap₅A concentrations were measured before and after hemodialysis using either polyacrylonitrile (AN69; n = 10) or polysulfone (n = 23) membranes. Ap₅A was isolated from platelets using affinity chromatography and reversed-phase chromatography methods. Results: The Ap₅A concentrations were quantified by ultraviolet absorption at 254 nm. The Ap₅A concentrations were significantly higher in platelets from the patients with end-stage renal failure as compared with the 21 healthy control subjects (136 ± 50 vs. 9 ± 6 fg/platelet; mean ± SEM, p < 0.01). Before hemodialysis, the intracellular Ap₅A concentrations in platelets from 10 patients with end-stage renal failure using an AN69 membrane were not significantly different from those in platelets from 23 patients using a polysulfone membrane (93 ± 39 vs. 155 ± 70 fg/platelet). However, after a hemodialysis session, the intracellular Ap₅A concentrations in platelets from patients with end-stage renal failure using an AN69 membrane were significantly lower as compared with those in platelets before hemodialysis (51 ± 18 vs. 93 ± 39 fg/platelet, p < 0.05) as well as compared with those in platelets from patients using a polysulfone membrane (51 ± 18 vs. 250 ± 59 fg/platelet, p < 0.05). Conclusions: It was found that hemofiltration by using an AN69 membrane has a direct effect on the intracellular amount of Ap₅A and that changes of intracellular hydrophilic substances are dependent on the hemodialysis membrane used.

Biocompatibility of Hemodialysis Membranes: Interrelations between Plasma Complement and Cytokine Levels

Hemodialysis (HD) membrane biocompatibility is defined as absence of complement activation. We have recently shown that circulating levels of interleukin (IL) 1 and IL-2 predict death and survival, respectively, of HD patients. Studies have assessed IL-1 in treatments with biocompatible and less biocompatible dialysis membranes, but no study has correlated circulating levels of all these immunoreactants. We assessed these immunoreactants, and temperature as an outcome, during HD in patients treated with different membranes. Twelve stable patients, receiving thrice-weekly chronic bicarbonate HD, were randomly dialyzed with three different types of membranes, composed of: Cuprophan, cuprammonium rayon modified cellulose, and Hemophan. Blood was drawn from the arterial line port before (Pre) and 15, 30, and 60 min during and after (Post) HD. Patients’ temperatures were measured before and after each treatment. The plasma concentrations of IL-1 and IL-2 and factors C3a and C5a were assessed by ELISA. There were no differences between baseline levels of any of the immunoreactants in patients treated with different dialyzers. C3a, C5a, and IL-1 levels increased significantly during HD treatments with all three different membranes. C3a, C5a, and IL-1 levels during Cuprophan and Hemophan treatments were significantly higher than the levels during modified cellulose treatment at 30 and 60 min and Post (p < 0.01). For all the immunoreactants, however, the Post levels were higher than the Pre levels. In contrast to IL-1, there were no differences in mean IL-2 levels during treatments when different membranes were compared. There were few correlations of plasma C3a and C5a levels with plasma IL-1 levels, but there was only one treatment time in one dialyzer group during which IL-2 and any of the other factors were correlated. Pre and Post temperature values and percent change in temperature were not correlated with any of the immunoreactants measured. These data show that C3a, C5a, and IL-1 responses are similar, but not identical, during treatments with different membranes. The response of circulating IL-2 levels to treatments is quite different from that of plasma C3a, C5a and IL-1 levels and suggests that these changes are not solely due to treatment factors. Treatment with modified cellulose membranes is associated with a different immunoreactive profile as compared with patients dialyzed using other cellulose membranes. We suggest that circulating IL-1 levels are good biocompatibility markers.

Prospective randomized study of hemodialysis membrane biocompatibility in acute renal failure

Prospective randomized study of hemodialysis membrane biocompatibility in acute renal failure

Rapid activation of the complement system by cuprophane depends on complement component C4

Rapid activation of the complement system by cuprophane depends on complement component C4

Determination of contact phase activation by the measurement of the activity of supernatant and membrane surface-adsorbed factor XII (FXII): Its relevance as a useful parameter for thein vitro assessment of haemodialysis membranes

We investigated hemodialysis membrane biocompatibility with respect to contact phase activation by determination of FXII-like activity (FXIIA) on the membrane surface and in the supernatant phase, during plasma contact with various hemodialysis membranes using an in vitro incubation test cell. The results were compared to the influence of these membranes on the activation of purified FXII. A time course for the generation of activated FXII using purified FXII solution at physiologic concentrations on two similar negatively charged polymers was performed. The membranes assessed were regenerated cellulose (Cuprophan; Akzo Faser AG, Germany), modified cellulosic (Hemophan; Akzo Faser AG), acrylonitrile-sodium methallyl copolymer-based membrane AN69S (Hospal, France), and SPAN, a new polyacrylonitrile-based copolymer (akzo Nobel AG). The plasma FXIIA at the membranes surface was significantly different between the membranes, while the supernatant phase FXIIA exhibited no significant differences. In contrast, activation of purified FXII in a plasma-free system with respect to supernatant activity indicated significant differences between the materials. A similar finding for the membrane-bound factor XIIA was also observed when purified factor XII was used. The membrane-bound FXIIA values observed in the plasma system containing heparin were significantly greater than in citrated plasma. This demonstrated the strong influence of heparin and the interaction of other plasma components to the membrane surface on the activation of contact phase of coagulation.

The role of platelet-activating factor in the biocompatibility of hemodialysis membranes.

Extracorporeal treatments for acute or chronic replacement of organ function still represent a challenge for today’s technology. Activation of fluid phase (complement, coagulation, fibrinolysis) and cellular systems (leukocytes, platelets) is known to occur in hemodialysis (1). Among other biochemical indications of leukocyte activation as a conseguence of blood-surface interactions such as oxygen radicals, release of granulocyte proteinases, monocyte prostaglandin release and cytokine generation, platelet-activating factor (PAF) has drawn interest in various biocompatibility studies (reviewed in 1–5). PAF is a phospholipid mediator of inflammation with different biologic properties relevant for the development of inflammation and septic shock (7–11). PAF may act at concentrations of 10−12M and requires an ether linkage at the sn-1 position of the glycerol backbone, a short acyl chain, usually an acetyl residue, at the sn-2 position, and the polar head group of choline or ethanolamine at the sn-3 position (7–8). However, it has been shown recently that PAF belongs to a family of structurally related phospholipid molecules of biologic origin that shares many physiologic activities (12). PAF is considered a mediator of cell-to-cell communication that may function both as an intracellular and intracellular messenger. PAF is produced after immunologic or nor immunologic challenge by a variety of cells such as monocytes/macrophages, polymorphonuclear neutrophils, basophils and platelets, that may participate in the development of inflammatory reaction (13). In addition, human endothelial cells were found to produce PAF after stimulation by several inflammatory mediators including thrombin, angiotensin II, vasopressin, leukotriene C4 and D4, histamine, bradykinin, elastase, catheprin G, and plastic (14–18). PAF acts in an autocrine and paracrine way through a specific receptor for which a cDNA has been cloned (19,20). The receptor belongs to the family of “serpentine” receptors containing sever a-helical domains that weave in and out plasma membrane and it interacts with a G protein, which activates a phosphatidylinositol-specific phospholipase C (19,20). PAF receptors exist in all cells that are known targets for PAF. Recently, also human cultured endothelial cells have been shown to express PAF receptors (21). PAF promotes the permeability of the EC monolayer leading to cell retraction and formation of intracellular gaps (22). PAF induces in vitro migration of endothelial cells and promotes in vivo angiogenesis by a heparin-dependent mechanism (21). The aim of the present review is to briefly summarize early evidence for a role of PAF in bioincompatibility events and to highlight recent advances and their possible potential practical application in testing polymer biocompatibility.KeywordsGlyceryl EtherShort Acyl ChainHaemodialysis MembraneExtracorporeal TreatmentSpontaneous AdherenceThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Ｉｎｔｅｒｌｅｕｋｉｎ‐８の遺伝子発現および血しょう濃度に対する血液透析の影響からみた透析膜の生体適合性

Ｉｎｔｅｒｌｅｕｋｉｎ‐８の遺伝子発現および血しょう濃度に対する血液透析の影響からみた透析膜の生体適合性

Biocompatibility of hemodialysis membranes: a study in healthy subjects.

The effect of blood-membrane interaction on several biocompatibility parameters has been investigated. Four groups of healthy subjects underwent sham hemodialysis, i.e. the establishment of blood-dialysis membrane contact, but without circulating dialysate, using cellulose-based membranes (regenerated cellulose and cellulose acetate) or synthetic membranes (polysulfone and polyacrilonitrile). Contact between blood and cellulose-based membranes resulted in pronounced complement activation and leukopenia whereas contact between blood and synthetic membranes induced weak complement reaction. The release of granulocytic elastase comparable to that obtained during clinical dialysis seemed to correlate directly with the types of membrane used. The gradual increase in the level of plasma elastase during blood-membrane contact, as opposed to the transient nature of the increase in the levels of complement, suggests that different mechanisms are responsible for these reactions. Nutritional implications of dialysis membrane bioincompatibility are discussed in the light of recently published metabolic data obtained in these subjects.

Biocompatibility of artificial organs: an overview.

Papers that are presented in this symposium on biocompatibility of foreign surfaces used in artificial organs are commented upon and set in an overall context of the biocompatibility of foreign surfaces to blood. A working formulation of the events comprising lack of biocompatibility of hemodialysis membranes to the complement system is given as a possible model to which other foreign surfaces may be compared.