Polyester Polymer Alloy Membrane Research Articles

Optimal Design of Dialyzers.

Several types of synthetic dialysis membranes, including polysulfone, polyethersulfone, and polyester polymer alloy membranes, have asymmetrical structures. Dialyzers with these membranes show higher water and solute transport performance because the actual membrane thickness, which is related to the water and solute transfer resistance, is quite small compared with that in membranes with a homogeneous structure. The performance of a dialyzer depends not only on membrane permeability to water and solutes, but also on flow conditions of the blood and dialysate, which are determined during dialyzer fabrication. Many types of high-flux dialyzers with high-performance membranes have a high internal filtration/backfiltration (IF/BF) flow rate. In the enhanced IF/BF dialyzer, membrane fouling occurs more readily than with the conventional dialyzer because of the high local transmembrane pressure needed to enhance the IF/BF flow rate. To select the optimal enhanced IF/BF dialyzer for individual patients, we need to balance the disadvantage of membrane fouling with the advantage of increased convective transport. Key Messages: The following principles should guide dialyzer development in the near term. (1) Dialyzers should show high performance for the removal of low-molecular-weight proteins related to certain complications under conditions of low albumin and amino acid loss. (2) Dialyzers with biocompatible membranes are required to prevent severe adverse reactions, even though the causal relationship between these reactions and some complications remains to be clarified.

Differences in the adsorption of nafamostat mesilate between polyester-polymer alloy and polysulfone membranes

We previously experienced severe clot formation in a polyester-polymer alloy (PEPA) dialyzer and hemodialysis (HD) circuit with nafamostat mesilate (NM) as an anticoagulant. The possibility of NM adsorption to the PEPA membrane was taken into consideration, but there was not enough information. In the present study, we evaluated differences in the adsorption of NM between a PEPA membrane (FDX-120 GW, Nikkiso, Tokyo, Japan) and two different polysulfone membranes (FX-140, Fresenius Medical Care, Tokyo, Japan; NV-15U, Toray Medical, Tokyo, Japan). We calculated the NM concentration by measuring absorbance at 241nm using a spectrometer. NM adsorption was evaluated in three ways. First, we evaluated NM adsorption to hollow fibers. Then, we passed an NM solution through dialyzers and evaluated its adsorption in a single-pass examination. Finally, we circulated an NM solution in an HD circuit using a blood pump and evaluated NM adsorption. In all the experiments, NM adsorption to the PEPA membrane was greater than that to the polysulfone membranes examined. In the blood pump experiment, the estimated adsorption quantities of NM to the PEPA membrane and the FX-140 and NV-15U polysulfone membranes were 12.0±0.1, 1.0±0.1, and 4.1±0.4mg/m2, respectively. NM adsorption was confirmed, especially in the early phase, and the PEPA membrane adsorbed greater amounts of NM than the polysulfone membranes. We should pay attention to the choice of dialyzer as well as the appropriate dose of NM administration during the preparation of HD circuits.

The past, present and future of the dialyzer.

Several types of dialysis membranes have been developed in the history of hemodialysis therapy. Regenerated cellulose had been widely used for a long time, since the beginning of dialysis therapy. Regenerated cellulose is strongly hydrophilic, which enables lower membrane thickness and miniaturization of the dialyzer. The cellulose triacetate membrane has greater performance because of the lower thickness of the membrane and its lack of swelling due to high hydrophobicity. Many types of synthetic membranes, such as polysulfone, polyethersulfone and polyester polymer alloy membranes, have asymmetrical structures. Dialyzers with these membranes show higher capacities for water and solute transport because the actual membrane thickness, which is related to the water and solute transfer resistance, is quite small compared to that in membranes with homogeneous structures. The development of highly biocompatible membranes will be required in the future so as to prevent the development of adverse reactions and related complications. The performance of a dialyzer depends not only on the membrane permeability but also on the flow conditions of the blood and dialysate. Many types of dialyzers with high-performance membranes have been developed as a result of advances in membrane and device technologies. Recently, many types of high-flux dialyzers with high-performance membranes with a high internal filtration (IF)/backfiltration (BF) flow rate have been introduced. IF-enhanced hemodialysis using an enhanced IF dialyzer seems to be more convenient than hemodiafiltration therapy because it requires no additional equipment, such as a roller pump. In the near future, dialyzers should be developed with high capacities for the removal of low-molecular-weight proteins (LMWPs) related to complications and with low capacities for the loss of albumin and amino acid. Dialyzers with a sharp cut-off membrane between LMWPs and albumin and dialyzers with a special function, i.e., an adsorptive property for some LMWPs, are required. In addition, dialyzers with biocompatible membranes are necessary to prevent severe adverse reactions, although the causal relationship between these reactions and some complications are yet to be clarified.

Nanoscale analysis of hydrophilicity–hydrophobicity distribution on inner surfaces of wet dialysis membranes by atomic force microscopy

Because protein adsorption depends significantly on the hydrophilicity–hydrophobicity of surfaces, it is important to evaluate nanoscale surface properties for improvement of the biocompatibility of dialysis membranes. The objective of the present study is to establish a nanoscale analytical method, which is independent of the test environment, for determining the hydrophilicity–hydrophobicity distribution on the inner surfaces of dialysis membranes. The hydrophobic adhesive forces to the wet dialysis membrane inner surfaces were determined using a hydrophobized atomic force microscopy probe, and the hydrophilicity–hydrophobicity distribution on the surfaces was visualized two-dimensionally at the nanoscale level. In addition, the relative intensity of hydrophobicity was examined by determining the ratio of the adhesive force to the test membrane inner surfaces to that to hydrophobized mica. The polysulfone (PSf) and polyester polymer alloy (PEPA) dialysis membranes decreased relative intensity of hydrophobicity on the inner surface with the addition of polyvinylpyrrolidone (PVP). The PEPA membrane inner surface had a more uniform hydrophilicity–hydrophobicity distribution with the PVP addition. On the other hand, the distribution on the PSf membrane inner surface remained uneven despite PVP addition. Our results demonstrate that it is possible to evaluate the hydrophilicity–hydrophobicity distributions on the surfaces of wet dialysis membranes using a hydrophobized probe.

Characterization of Insulin Adsorption Behavior of Dialyzer Membranes Used in Hemodialysis

Although it has been reported that plasma insulin is removed by hemodialysis (HD), the mechanism for this has not been elucidated. We investigated the mechanism of insulin removal during HD treatment and the characteristics of insulin removal with three high-flux membranes. In our in vivo study, 20 stable diabetic patients on HD were randomly selected for three HD sessions with three different membranes: polysulfone (PS), cellulose triacetate (CTA), and polyester polymer alloy (PEPA). Blood samples were obtained from the blood tubing at the arterial (A) site at the beginning and end of the sixth HD session to investigate insulin reduction in patients. At 1 h after the initiation of dialysis, blood samples were obtained from both the A and venous sites of the dialyzer to investigate the insulin clearance with the different membranes. There was a significant reduction in patients' plasma insulin at each time point with each of the three membranes. The insulin clearance with the PS membrane was significantly higher than that with the CTA and PEPA membranes. Although no difference was observed in the plasma insulin reduction rate between the three membranes in the total subject group, there was a significantly higher reduction rate with the PS membrane in insulin-dependent diabetes mellitus subjects. The clearance of insulin in in vitro tests was significantly higher with the PS and PEPA membranes than with the CTA membrane in both new and clinically used dialyzers. Insulin was not detected in the dialysate or ultrafiltration fluids in either the in vivo or in vitro studies. The mechanism of plasma insulin clearance by HD is mainly by adsorption, and the amount of insulin adsorbed differed depending on the dialyzer membrane used.

Functional-group analysis of polyvinylpyrrolidone on the inner surface of hollow-fiber dialysis membranes, by near-field infrared microspectroscopy

Near-field infrared microspectroscopy (NFIR) is a newly developed surface analysis method that is based on functional-group analysis and has a high spatial resolution. The objective of the present study is to perform nanoscale functional-group analysis of dialysis membrane surfaces by using NFIR. We focused on polyvinylpyrrolidone (PVP), which is employed as an additive to hydrophilize and create pores in synthetic polymer dialysis membranes, and evaluated the PVP distribution on the inner surface of the dialysis membranes. Dialysis membranes made from polysulfone (PSf) and polyester–polymer alloy (PEPA) were first assessed by NFIR and then by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). The nanoscale NFIR analysis showed heterogeneous distribution of PVP on the PSf membrane even though the amount of PVP on the membrane surface was high. PVP was homogeneously distributed on the PEPA membrane even though the amount of PVP on the membrane surface was low. In contrast, the microscale ATR-FTIR results showed that PVP was homogeneously distributed on both PSf and PEPA membranes. PVP-rich and PVP-poor regions were distinguishable by NFIR and not by ATR-FTIR, because the spatial resolution of NFIR is higher than that of ATR-FTIR. This study demonstrates for the first time that NFIR can provide nanoscale chemical information on the structures of porous membranes.

Effect of packing density of hollow fibers on solute removal performances of dialyzers

Solute removal performances of dialyzers are dependent not only on the solute permeabilities of the membrane but also on the module design. We have investigated how the packing density of hollow fiber (PDF) affects the solute removal performances. A series of 4 polyester polymer alloy membrane test dialyzers were assembled with varying PDFs of 29.6%, 35.3%, 44.1%, and 53.1%. Clearances (C(L)) were measured in vitro for creatinine (MW113), vitamin B(12) (MW1355), and chymotrypsin (MW25300) with various Q(B)=100 to 400 and Q(D)=350 to 650 mL/min in the absence of net ultrafiltration. When Q(B) was <or=300 mL/min, no significant changes were found in creatinine C(L) with the increase of PDF up to 35.3%. A slightly greater increase was found in C(L) when Q(B)=400 mL/min. Clearances for vitamin B(12), however, increased with the increase of PDF in the range of 29.6% to 35.3%. The effects of PDF on C(L) were greater with larger Q(B). More importantly, an abrupt increase of C(L) was found when PDF was increased from 44.1% to 53.1%. According to a rigorous mathematical model, this may be caused by the internal filtration, which is reverse ultrafiltration occurring in a dialyzer at any given time. No significant increase was found in chymotrypsin C(L) when the PDF was <or=35.3%, which suggested that C(L) for large molecules was strongly dependent on the solute permeability rather than the conditions of flow patterns. A very steep increase was also found in C(L) for chymotrypsin when the PDF was >44.1%, which was also considered to be due to the internal filtration. Packing density of hollow fiber can be optimized in terms of solute removal performances when the target solute and therapeutic conditions are specified.

Nanotechnological Characterization of Human Serum Albumin Adsorption on Wet Synthetic Polymer Dialysis Membrane Surfaces

The objective of the present study was to evaluate the characteristics of protein adsorption on the inner surface of various dialysis membranes, to develop protein adsorption-resistant biocompatible dialysis membranes. The adsorption force of human serum albumin (HSA) on the inner surface of a dialysis membrane and the smoothness of the membrane were evaluated from a nanoscale perspective by atomic force microscopy. The content ratio of the hydrophilic polymer, polyvinylpyrrolidone (PVP), was determined by attenuated total reflection Fourier transform infrared spectroscopy. Nine synthetic-polymer dialysis membranes on the market made of polysulfone (PSF), polyethersulfone (PES), polyester polymer-alloy (PEPA), and ethylene vinylalcohol (EVAL) were used in the present study. The HSA adsorption force on the surface of the hydrophobic polymer PEPA membrane was higher than that on the hydrophilic polymer EVAL membrane surface. It has been considered beneficial, for decreasing the HSA adsorption force, to cover a hydrophobic polymer membrane surface with PVP. However, there were some areas on PVP-containing membrane surfaces at which much higher HSA adsorption forces were observed. The HSA adsorption force gave a nearly linear correlation with the surface roughness on the PSF membrane surface. However, the HSA adsorption force was uncorrelated with the PVP content ratio for any of the PSF membrane surfaces tested. In conclusion, protein adsorption can be minimized by the use of dialysis membranes made of hydrophobic polymers containing PVP with a smooth surface.

Effects of fluid flow on elution of hydrophilic modifier from dialysis membrane surfaces

When uremic blood flows through dialyzers during hemodialysis, dialysis membrane surfaces are exposed to shear stress and internal filtration, which may affect the surface characteristics of the dialysis membranes. In the present study, we evaluated changes in the characteristics of membrane surfaces caused by shear stress and internal filtration using blood substitutes: water purified by reverse osmosis and 6.7 wt% dextran70 solution. We focused on the levels of a hydrophilic modifier, polyvinylpyrrolidone (PVP), on the membrane surface measured by attenuated total reflectance Fourier transform infrared spectroscopy. Experiments involving 4 h dialysis, 0-144 h shear-stress loading, and 4 h dead-end filtration were performed using polyester-polymer alloy (PEPA) and polysulfone (PS) membranes. After the dialysis experiments with accompanying internal filtration, average PVP retention on the PEPA membrane surface was 93.7% in all areas, whereas that on the PS membrane surface was 98.9% in all areas. After the shear-stress loading experiments, PVP retention on the PEPA membrane surface decreased as shear-stress loading time and the magnitude of shear stress increased. However, with the PS membrane, PVP retention scarcely changed. After the dead-end filtration experiments, PVP retention decreased in all areas for both PEPA and PS membranes, but PVP retention on the PEPA membrane surface was lower than that on the PS membrane surface. PVP on the PEPA membrane surface was eluted by both shear stress and internal filtration, while that on the PS membrane surface was eluted only by internal filtration.

The influence of hemodialysis membranes on the plasma insulin level of diabetic patients on maintenance hemodialysis

The aim of the present study was to evaluate the alteration in plasma immunoreactive insulin (IRI) concentrations due to hemodialysis (HD) treatment by using three types of membranes in diabetic HD patients. We recruited 20 outpatients on maintenance HD with diabetes for this crossover study. HD was performed using membranes made of cellulose triacetate (CTA), polyester-polymer alloy (PEPA), and polysulphone (PS). These membranes were used for 2 weeks (6 HD sessions) in each patient in a randomized order decided by drawing lots. Blood samples were obtained at the beginning and end of the HD session from the blood tubing at the arterial (A) site. At 60 min after the initiation of dialysis, blood samples were obtained from the blood tubing at both the A and venous (V) sites of the dialyzer. The plasma IRI levels decreased significantly at the sites an hour after initiating HD in all membranes. The clearance of IRI was significantly higher in the case of the PS membrane when compared with the CTA and PEPA membranes. It was concluded that plasma insulin is cleared by HD, and the rate differs for each membrane. Plasma insulin clearance with the PS membrane is higher than that with the PEPA and CTA membranes.

Blood compatibility and filtration characteristics of a newly developed polyester polymer alloy membrane

Many synthetic polymeric membranes have been widely used for blood purification therapies for removing larger solutes and for better blood compatibility. Five different filters with polyester polymer alloy (PEPA) membrane (Nikkiso) that included polyvinylpyrrolidone (PVP), that is, standard-pore-size FLX (PEPA with PVP(-)), standard-pore-size FDX (PEPA with PVP(+)), new FDX (PEPA with PVP(++)), larger-pore-size FDY (PEPA with PVP(+)), and new FDY (PEPA with PVP(++)), were evaluated in terms of in vivo blood compatibility and aqueous in vitro sieving coefficient (s.c.) for albumin. FDY showed excellent small changes in C3a concentration during the treatment right after switching from polysulfone membrane, leaving no significant changes in other blood-compatible indices. New FDY, in contrast, showed less biocompatible characteristics in terms of C3a, which may be caused by increased use of PVP. FLX (no PVP) showed the highest s.c. for albumin. With a hydrophilic agent (PVP), the s.c. was greatly reduced in FDX. By enlarging the pore diameter in FDY, the s.c. increased in accordance with the enlargement. Generally speaking, polysulfone filters with PVP(+++) reach the peak s.c. value approximately 10 min after starting the experiment. The s.c. of the PEPA membrane with no or small amount of PVP, which showed excellent blood compatibility, never showed peaks, whereas the peak s.c. values were found in new PEPA with increased amount of PVP that showed higher C3a changes. The separation characteristics of aqueous albumin may be related to its blood compatibility.

Blood Compatibility and Filtration: Characteristics of Newly Developed Polyester Polymer Alloy Membrane

Many synthetic polymeric membranes have been widely used for blood purification therapies. Among them polyester polymer alloy (PEPA) membrane shows unique blood compatibility and filtration characteristics.Objective: To evaluate blood compatibility and filtration characteristics of 3 different PEPA membranes, including FLX (PEPA only), FDX (PEPA with polyvinylpyrrolidone, (PVP) as a hydrophilic agent), and FDY (PEPA with PVP) that has larger pore diameter.Methods: Ultrafilters with 3 PEPA membranes (FLX, FDX, FDY, Nikkiso, Tokyo) were compared with those with polysulfone (PS; NK‐PS, Nikkiso, Tokyo) for blood compatibility in vivo. Also, ultrafilters with PEPA, PS, and cellulose triacetate (CTA; FB‐110GA, Nipro, Osaka) membranes were also investigated for filtration characteristics of albumin in aqueous in vitro.Results: FDY, the latest version of the three PEPA, showed excellent small changes in C5a concentration during the treatment right after switching from PS membrane, leaving no significant changes in other biocompatible indices. First 60 min of the time course of s.c. for albumin were shown below taken under aqueous low albumin concentration, i.e., 2.42 × 10−3 kg/dm3. The time‐dependent patterns were totally different from each other in 5 filters. Generally speaking, PS takes a peak value 20–40 min after starting the experiment, depending on the flow conditions. Since PEPA is a hydrophobic material, it showed high s.c. for albumin in FLX (PEPA with no PVP) and never reached plateau. With a hydrophilic agent (PVP), the s.c. greatly reduced in FDX and showed little time‐dependent change. By enlarging the pore diameter in FDY, the s.c. increased in accordance with the enlargement.Conclusion: Newly developed PEPA with PVP has excellent blood compatibility and has unique separation characteristics for albumin.