Permeability Of Dialysis Membranes Research Articles

Expanded hemodialysis: new opportunities and hopes

In the field of hemodialysis technologies, as in other fields of medicine, evolutionary changes are constantly taking place. The innovations are driven by unachieved clinical outcomes and desire to improve the quality of care of patients with CKD 5D. Recent advances in dialysis techniques resulted in the possibility to expand the permeability of dialysis membranes for a wider spectrum of uremic toxins that lead to the enhancement of long-term outcomes improving quality of life and reducing the mortality rate of dialysis patients. The inadequacy of existent dialysis techniques, at least in part, is due to the chronic accumulation of organic retention solutes of middle and large molecules, which are poorly or even not removed during dialysis.
 A gradual improvement in the elimination of uremic toxins is observed as a result of the development of new alternative approaches of hemodialysis therapy, such as high-flux hemodialysis, hemodiafiltration, expanded hemodialysis (HDx). However, some techniques have had limited success due to a host number of organizational, technological, financial and human factors. Expanded hemodialysis offers a novel blood purification technology in removal of the large spectrum of uremic toxins, in particular large medium molecules, due to the new structure of the dialysis membrane. There are a number of studies that prove the potential benefits of a new method of dialysis therapy over the previous ones, suggesting a reduction in cardiovascular mortality, vascular calcification and inflammation. In addition, there is evidence of a positive effect of HDx on the quality of life in dialysis patients. In particular, to minimize the manifestations of skin itching, restless legs syndrome, asthenic syndrome.

Advantages of expanded hemodialysis (HDx) over standard hemodialysis

Chronic kidney disease leads to the accumulation of a wide range of uremic toxins. Negative effects of uremic toxins are most likely due to the combined effects of many uremic solutes, including small molecules, middle molecules, and soluble protein-linked substances. Large and medium-sized molecules are directly associated with chronic inflammation and adverse effects, including major cardiovascular risks and consequently poor prognosis.
 Recent advances in chemical composition and new production techniques led to improved biocompatibility and selective permeability of dialysis membranes. Specifically, the creation of a new class of membranes provided the possibility to improve the clearance of medium to high molecular weight (MW) solutes (i.e. uremic toxins in the range of 5–50 kDa).
 The new HDx therapy (expanded HD) is the next evolution in hemodialysis, as it effectively targets the removal of large middle molecules. The HDx therapy is enabled by the THERANOVA dialyzer featuring an innovative membrane that combines a higher permeability than regular high-flux dialyzers with effective selectivity for large proteins.
 Expanded hemodialysis is an advanced therapy targeting large and medium-sized molecules that are currently not possible to remove by modern dialysis methods including traditional hemodialysis (HD) and hemodiafiltration (HDF). HDx became possible due to THERANOVA, a new dialyzer with an innovative membrane. The THERANOVA-based HDx provides a great new opportunity for dialysis patients, providing unique high-efficiency hemodialysis with the usage of already available infrastructure and standard HD workflows.

Expanded haemodialysis: from operational mechanism to clinical results.

Recent advances in chemical composition and new production techniques resulted in improved biocompatibility and permeability of dialysis membranes. Among these, the creation of a new class of membranes called medium cut-off (MCO) represents an important step towards improvement of clinical outcomes. Such membranes have been developed to improve the clearance of medium to high molecular weight (MW) solutes (i.e. uraemic toxins in the range of 5–50 kDa). MCO membranes have peculiar retention onset and cut-off characteristics. Due to a modified sieving profile, MCO membranes have also been described as high-retention onset. The significant internal filtration achieved in MCO haemodialysers provides a remarkable convective clearance of medium to high MW solutes. The marginal loss of albumin observed in MCO membranes compared with high cut-off membranes is considered acceptable, if not beneficial, producing a certain clearance of protein-bound solutes. The application of MCO membranes in a classic dialysis modality characterizes a new technique called expanded haemodialysis. This therapy does not need specific software or dedicated hardware, making its application possible in every setting where the quality of dialysis fluid meets current standards.

Mathematical and Experimental Validation of Flux Dialysis Method: An Improved Approach to Measure Unbound Fraction for Compounds with High Protein Binding and Other Challenging Properties.

A flux dialysis method to measure unbound fraction (fu) of compounds with high protein binding and other challenging properties was tested and validated. This method is based on the principle that the initial flux rate of a compound through a size-excluding dialysis membrane is proportional to the product of the compound initial concentration, fu, and unbound dialysis membrane permeability (Pmem). Therefore, fu can be determined from the initial concentration and flux rate, assuming membrane Pmem is known. Compound initial flux rates for 14 compounds were determined by dialyzing human plasma containing compound (donor side) versus compound-free plasma (receiver side) and measuring the rate of compound appearance into the receiver side. Eleven compounds had known fu values obtained from conventional methods (ranging from 0.000013 to 0.22); three compounds (bedaquiline, lapatinib, and pibrentasvir) had previously qualified fu values (e.g., <0.001).Pmem estimated from flux rates and known fu values did not meaningfully differ among the compounds and were consistent with previously published values, indicating that Pmem is a constant for the dialysis membrane. This Pmem constant and the individual compound flux rates were used to calculate fu values. The flux dialysis fu values for the 11 compounds were in good agreement with their reported fu values (all within 2.5-fold; R2 = 0.980), confirming the validity of the method. Furthermore, the flux dialysis method allowed discrete fu to be estimated for the three compounds with previously qualified fu Theoretical and experimental advantages of the flux dialysis method over other dialysis-based protein binding methods are discussed.

Precise Quantitative Assessment of the Clinical Performances of Two High-Flux Polysulfone Hemodialyzers in Hemodialysis: Validation of a Blood-Based Simple Kinetic Model Versus Direct Dialysis Quantification.

Highly permeable dialysis membranes with better design filters have contributed to improved solute removal and dialysis efficacy. However, solute membrane permeability needs to be well controlled to avoid increased loss of albumin that is considered to be detrimental for dialysis patients. A novel high-flux dialyzer type (FX CorDiax; Fresenius Medical Care) incorporating an advanced polysulfone membrane modified with nano-controlled spinning technology to enhance the elimination of a broader spectrum of uremic toxins has been released. The aim of this study was to compare in the clinical setting two dialyzer types having the same surface area, the current (FX dialyzer) and the new dialyzer generation (FX CorDiax), with respect to solute removal capacity over a broad spectrum of markers, including assessment of albumin loss based on a direct dialysis quantification method. We performed a crossover study following an A1-B-A2 design involving 10 patients. Phase A1 was 1 week of thrice-weekly bicarbonate hemodialysis with the FX dialyzer, 4 h per treatment; phase B was performed with a similar treatment regimen but with a new FX CorDiax dialyzer and finally the phase A2 was repeated with FX dialyzer as the former phase. Solute removal markers of interest were assessed from blood samples taken before and after treatment and from total spent dialysate collection (direct dialysis quantification) permitting a mass transfer calculation (mg/session into total spent dialysate/ultrafiltrate). On the blood side, there were no significant differences in the solute percent reduction between FX CorDiax 80 and FX 80. On the dialysate side, no difference was observed regarding eliminated mass of different solutes including β2 -microglobulin (143.1 ± 33.6 vs. 138.3 ± 41.9 mg, P = 0.8), while the solute mass removal of total protein (1.65 ± 0.51 vs. 2.14 ± 0.75 g, P = 0.04), and albumin (0.41 ± 0.21 vs. 1.22 ± 0.51 g, P < 0.001) were significantly less for FX CorDiax 80 compared to the FX 80 dialyzer. The results of this cross-over study indicate that the new FX CorDiax dialyzer has highly effective removal of middle molecules, without any concomitant increase in total protein and albumin loss. The clinical relevance and potential benefit of this finding needs to be determined.

Evaluation of blood adsorption onto dialysis membranes by time-of-flight secondary ion mass spectrometry and near-field infrared microscopy.

Blood adsorption onto the inside surface of hollow fiber dialysis membranes was investigated by means of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and near-field infrared microscopy (NFIR) in order to evaluate the biocompatibility and permeability of dialysis membranes. TOF-SIMS is useful for the imaging of particular molecules with a high spatial resolution of approximately 100nm. In contrast, infrared spectra provide quantitative information and NFIR enables analysis with a high spatial resolution of less than 1μm, which is close to the resolution of TOF-SIMS. A comparison was made of one of the most widely used dialysis membranes made of polysulfone (PSf), that has an asymmetric and inhomogeneous pore structure, and a newly developed asymmetric cellulose triacetate (ATA) membrane that also has an asymmetric pore structure, even though the conventional cellulose triacetate membrane has a symmetric and homogeneous pore structure. As a result, it was demonstrated that blood adsorption on the inside surface of the ATA membrane is more reduced than that on the PSf membrane. Graphical abstract Analysis of blood adsorption on inside surface of hollow fiber membrane.

Analytical and Finite Element Modeling of Nanomembranes for Miniaturized, Continuous Hemodialysis.

Hemodialysis involves large, periodic treatment doses using large-area membranes. If the permeability of dialysis membranes could be increased, it would reduce the necessary dialyzer size and could enable a wearable device that administers a continuous, low dose treatment of chronic kidney disease. This paper explores the application of ultrathin silicon membranes to this purpose, by way of analytical and finite element models of diffusive and convective transport of plasma solutes during hemodialysis, which we show to be predictive of experimental results. A proof-of-concept miniature nanomembrane dialyzer design is then proposed and analytically predicted to clear uremic toxins at near-ideal levels, as measured by several markers of dialysis adequacy. This work suggests the feasibility of miniature nanomembrane-based dialyzers that achieve therapeutic levels of uremic toxin clearance for patients with kidney failure.

Joint Modeling of All-Cause Mortality and Longitudinally Measured Serum Albumin

In clinical studies, longitudinal and survival data are often obtained simultaneously from the same individual. Linear mixed effects models are widely used for analyzing longitudinal continuous outcome data, while survival models are used for analyzing time-to-event data. It is a common practice to analyze these longitudinal and time-to-event data separately. However, when multivariate outcomes are obtained from a given individual, they can be correlated by nature, and one can attain considerable gain in efficiency by jointly analyzing the outcomes. An objective of this study is to analyze such multivariate data by jointly modeling longitudinally measured continuous outcomes and time-to-event data. In this joint modeling, we formulate a joint likelihood function for both outcomes and use the maximum likelihood method to estimate the parameters in the two sub-models (longitudinal and survival models). We demonstrate the merits of joint modeling by considering a joint analysis of longitudinally measured serum albumin (biomarker) and time-to-all-cause mortality data obtained from a hemodialysis (HEMO) study. This HEMO study was a large NIH (National Institute of Health) sponsored multicenter clinical trial contrasting the effects of dialysis dose and dialysis membrane permeability in end-stage renal disease patients receiving hemodialysis. We find that the parameter estimates obtained under joint modeling of HEMO data are more efficient than those obtained under separate modeling of the outcome variables.

Effects of a polyelectrolyte additive on the selective dialysis membrane permeability for low-molecular-weight proteins

Improving the sieving characteristics of dialysis membranes enhances the clearance of low-molecular-weight (LMW) proteins and may have an impact on outcome in patients receiving haemodialysis. To approach this goal, a novel polyelectrolyte additive process was applied to a polyethersulphone (PES) membrane. Polyelectrolyte-modified PES was characterized in vitro by measuring complement activation and sieving coefficients of cytochrome c and serum albumin. In a prospective, randomized, cross-over study, instantaneous plasma water clearances and reduction rates of LMW proteins [beta(2)-microglobulin (b2m), cystatin c, myoglobin, retinol binding protein] were determined in eight patients receiving dialysis treatment with PES in comparison with polysulphone (PSU). Biocompatibility was assessed by determination of transient leucopenia, plasma levels of complement C5a, thrombin-antithrombin III (TAT), myeloperoxidase (MPO) and elastase (ELT). PES showed a steeper sieving profile and lower complement activation in vitro compared with PSU. Instantaneous clearance (69 +/- 8 vs. 58 +/- 3 ml/min; P < 0.001) and reduction rate (72.3 +/- 1 5% vs 66.2 +/- 6.1%; P < 0.001) of b2m were significantly higher with PES as compared with PSU. With higher molecular weight of proteins, differences in the solute removal between PES and PSU further increased, whereas albumin loss remained low (PES, 0.53 +/- 0.17 vs PSU, <0.22 g/dialysis). MPO, ELT and TAT did not differ between the two membranes. In contrast, leucopenia was less pronounced and C5a generation was significantly lower during dialysis with PES. Polyelectrolyte modification of PES results in a higher LMW protein removal and in optimized biocompatibility. Whether these findings translate into better outcome of patients receiving haemodialysis requires further studies.

UNRESOLVED ISSUES IN DIALYSIS: Ultrapure Dialysate: Facts and Myths

ABSTRACTDuring hemodialysis, blood comes in contact with a large volume of dialysate. Since the purity of dialysate has been linked to acute and long‐term complications in hemodialysis patients, the limit of bacterial and endotoxin contamination has been reduced in recent years. Questions have been raised as to whether ultrapure dialysate is required to prevent such complications; in particular, the chronic inflammatory status frequently found in chronically hemodialyzed patients. In vivo and in vitro data suggest that cytokine stimulation in the blood depends on the concentration of bacteria or endotoxin in the dialysate and on the endotoxin permeability of the dialysis membrane. It is not proven whether ultrapure dialysate reduces significantly proinflammatory cytokine generation compared with standard dialysate within the limits of recent recommendations, if rather impermeable dialysis membranes are used. Cuprophane membranes are more permeable to cytokine‐inducing substances compared with synthetic membranes such as polysulfone and polyamide. Clinical reports have also attempted to link several acute and chronic complications of hemodialysis to dialysate purity. To date, however, there is no large randomized clinical trial demonstrating that ultrapure dialysate significantly reduces biomarkers of inflammation and other consequential putative complications, including dialysis‐related amyloidosis, erythropoietin requirement, and cardiovascular morbidity and mortality. In conclusion, based on the existing clinical data, ultrapure dialysate is recommended in the setting of suboptimal bacteriologic quality of standard dialysate and the use of permeable dialysis membranes.

Lymphocyte Apoptosis: Role of Uremia and Permeability of Dialysis Membrane

Background: Uremia is associated to host defense mechanism disorders. Lymphocyte apoptosis, which may cause alteration of the immune system, is increased in uremic patients. The aim of the present study was to determine if, in addition to uremia, dialysis membranes with different biocompatibility and permeability have an effect on lymphocyte apoptosis. Methods: Cell apoptosis and Fas expression were assessed using flow cytometry in four groups of patients: (1) uremic non-dialyzed (Non-D) patients; (2) hemodialysis (HD) patients on hemophan; (3) low-flux polysulfone, and (4) high-flux polysulfone membrane. Ten healthy volunteers were used ascontrols. Results: At baseline, lymphocytes from patients on hemophan showed an increase in apoptosis (18.4 ± 6.9%) as compared with Non-D (7.2 ± 2.8%; p < 0.001), low-flux (6.4 ± 2.4%; p < 0.001), high-flux (2.6 ± 1.2%; p < 0.001) and controls (2.0 ± 1.0%; p < 0.001). Fas expression was similar in lymphocytes from Non-D and hemophan dialyzed patients (40.5 ± 5% vs. 40.4 ± 6%), and in both groups it was greater than low-flux (30%±7%; p < 0.001), high-flux (11 ± 4%; p < 0.001) and controls (12.6 ± 3%; p < 0.001). When lymphocytes were cultured for 48 h, apoptosis was similar in Non-D and hemophan (27.0 ± 4.3% vs. 27.1 ± 6.9%); apoptosis of lymphocyte from patients on low-flux (14.1 ± 3.5%) was greater than on high-flux polysulfone membrane (7.0 ± 2.0%; p < 0.001). Conclusion: These findings suggest that in dialysis patients lymphocyte apoptosis is influenced not only by the biocompatibility but also by the permeability of the dialysis membrane.

Visualization of distribution of endotoxin trapped in an endotoxin-blocking filtration membrane

Since the finding of β 2-microglobulin as a causal substance in the carpal tunnel syndrome of chronic hemodialysis patients, removal of β 2-microglobulin has been performed using highly permeable dialysis membranes with larger pores. Such large-pore membranes tend to allow endotoxins (Et), harmful substances contained in dialysate, to enter blood. At present, as a countermeasure, Et-blocking filtration membranes are used to remove Et from dialysate. However, Et removal mechanism by these membranes has not been clarified yet. The objective of this study is thus to visualize distribution of fluorescence-labeled Et trapped inside the polyester–polymer alloy (PEPA) membrane, a widely used Et-blocking filtration membrane using a confocal laser scanning fluorescence microscope (CLSFM). Et were observed mainly in the outer skin layer of the hollow fiber, while some in the void and inner skin layers. No Et were present inside the hollow fiber. In conclusion, we succeeded in visualization of Et distribution inside the Et-blocking filtration membrane using CLSFM. This novel visualization technique may allow evaluation of distribution of Et trapped inside various kinds of Et-blocking filtration membranes.

Impact of Hemodialysis Membrane and Permeability on Neutrophil Transmigration in vitro

Background/Aim: The impact of dialysis membrane permeability on neutrophil transmigration properties in vitro was examined in the present study. This issue has not been fully scrutinized before. Methods: We studied the capacity of neutrophils collected from a group of dialysis patients randomly treated with cuprophan, low- or high-flux polysulfone, to transmigrate in vitro through a membrane covered with fibronectin (a main constituent of the endothelial basement membrane). The hemodialysis-induced quantitative changes in expression of adhesion molecules were examined in parallel. Results: At the end of dialysis, neutrophils collected from patients treated with high-flux polysulfone dialyzers had a significantly higher transmigration index than neutrophils from patients treated with low-flux polysulfone membrane (p < 0.01) or cuprophan membrane (p < 0.01), and approached the level of transmigration observed in neutrophils collected from healthy controls. In the groups treated with low-flux polysulfone and cuprophan dialyzers, the transmigration capacity was significantly lower (p < 0.02) compared to neutrophils from healthy subjects. We also noted that differences between low- and high-flux polysulfone dialysis, in the context of transmigration properties, were not mirrored by changes in adhesion phenotype, which strengthens the view that there is no strict relationship between these two features. Conclusion: The study demonstrates that high-flux polysulfone dialysis, as opposed to low-flux polysulfone and cuprophan treatment, improves the transmigration properties of circulating neutrophils, despite similar effects on adhesion molecule phenotypes. A plausible mechanism is that potentially toxic middle range molecules that inhibit neutrophil migration are more efficiently eliminated during high-flux polysulfone dialysis, but this explanation requires further support.

Does treatment modality have an impact on anemia in patients with chronic renal failure? Effect of low- and high-flux biocompatible dialysis.

Renal anemia significantly affects the morbidity and mortality of dialysis patients. The aim of the present study was to establish whether the severity of anemia and success of its treatment differs when using high-flux (HF) or low-flux (LF) hemodialysis. Twenty-five patients on long-term hemodialysis with a mean hematocrit (Hct) of 33%, S alb of 36 g/L, and Kt/V urea of 1.5 were divided into Groups X (n = 13) and Y (n = 12) in a prospective randomized crossover study. Group X was initially treated with LF hemodialysis to be followed by HF hemodialysis for 8 weeks each time. Group Y started with 8 week HF hemodialysis and continued, after crossover, with 8 weeks of LF hemodialysis. HF and LF hemodialysis were performed with polysulfone dialyzers F 7HPS and F60S (Fresenius Medical Care, Bad Homburg, Germany). Hct values, examined at 2 week intervals, did not differ significantly between Groups X and Y during 16 weeks of the study at any measuring interval. In another analysis, all results of HF hemodialysis (first 8 weeks of Y + second 8 weeks of X) were pooled as were all data of LF hemodialysis (first 8 weeks of X + second 8 weeks of Y). No significant relationships were noted between duration of treatment with HF hemodialysis and Hct (n = 72, rS = 0.11, p = 0.36) and between duration of LF hemodialysis and Hct (n = 74, rS = 0.02, p = 0.87) in the newly formed groups. The Hct measured during HF hemodialysis and LF hemodialysis did not differ significantly. Analysis of variance did not reveal a relationship between Hct and the HF or LF membrane. As HF and LF hemodialysis differed significantly in Kt/V urea, the variables were adjusted to identical Kt/V urea using analysis of covariance. No relationship between Hct and dialysis membrane permeability was demonstrated even in this case. Use of biocompatible LF and HF membranes in standard hemodialysis modes under conditions of adequate dose of dialysis and the time period studied did not result in different effects on anemia.

Filtration of native and glycated β2-microglobulin by charged and neutral dialysis membranes

It has been postulated that protein glycation and formation of advanced glycation end products (AGE) are among toxic factors in chronic uremia, whether the renal disease is of diabetic or nondiabetic origin. In this setting, AGE-modified beta2-microglobulin (beta2m) may favor dialysis beta2m-related dialysis amyloidosis. Consequently, efficient removal of modified beta2m by highly permeable dialysis membranes is as important as removal of native beta2m to postpone the development of dialysis amyloidosis. To define the role of dialysis membrane surface electronegativity on plasma protein transfer, an in vitro model was used to test the interactions of native and glycated beta2m with various highly permeable dialysis membranes. An experimental circuit with minidialyzers was used. The neutral high-flux polysulfone membrane (PS), the electronegative polymethylmetacrylate membrane (PMMA), the electronegative AN69 membrane and a modified AN69 membrane, the surface of which was neutralized with polyethyleneimine (AN69-PEI), were tested using both native beta2m and the more acidic glycated beta2m. Protein mass transfer and binding to the membrane were measured. Mass transfer of glycated beta2m was significantly decreased through all membranes tested when compared with native beta2m. This result was due to the increased molecular weight of beta2m, which became less permeable to porous membranes, whereas adsorption of both native and glycated beta2m to membranes, due to ionic interactions, decreased similarly with AN69 and AN69-PEI, but remained unchanged with PS and PMMA. Moreover, surface neutralization of AN69 membrane did not alter its core binding capacity, since beta2m absorption accounted for 98 and 97% and glycated beta2m for 83.7 and 81.4% of the protein removed with AN69 and AN69-PEI, respectively. Clearance of glycated beta2m through highly permeable neutral and negatively charged membranes was lower than that of native beta2m, reflecting a decreased sieving coefficient for the neoformed higher molecular weight and conformationally altered molecule. The binding capacity of the neutral PS was roughly half that of the charged membranes. Neutralizing surface electronegativity of the AN69 membrane with PEI did not alter its binding capacity. These results suggest that it would be useful for dialysis protocols to include comparative studies of both serum native and modified beta2m in order to prevent beta2m-amyloidosis.

非対称構造を有する透析膜の膜内拡散係数および阻止率とそれらのファウリングによる変化

One of the factors to reduce the performance of a hemodialyzer during clinical treatment is membrane fouling caused by protein adsorption. Highly permeable dialysis membranes recently developed are of asymmetrical structure and the reduction in permeability after protein adsorption may vary with their asymmetrical structure. Intramembrane diffusion coefficients and rejection factor for several solutes of polysulfone membranes having asymmetrical structure were measured before and after plasma protein adsorption. Ratio of intramembrane diffusion coefficient to diffusion coefficient in water for higher molecular weight solutes is reduced after plasma protein adsorption, but that for lower molecular weight solutes is slightly reduced. Rejection factor after plasma protein adsorption increases at lower filtration flux especially for smaller molecules, but that at higher filtration flux hardly changes.

Effect of Ultrasonic Irradiation on Permeability of Dialysis Membrane

The application of ultrasound for accelerating the diffusion of electrolytes through a membrane has been attempted. However, the effect of ultrasound on membrane permeability was not clarified in previous studies. we report the relationship between the time of ultrasound irradiation to membrane and permeability of the membrane, and the relationship between sound pressure and the membrane lifetime. Experiments were conducted using a cellophane membrane which had been irradiated for a certain time by ultrasound of different sound pressures at a frequency of 27.5 kHz, and the permeability of the membrane was examined with 1 wt% NaCl solution at 25° C. It was found that the membrane permeability increases with irradiation time. Furthermore, the lifetime of membrane decreases with increasing sound pressure. The degradation of the permeability by ultrasound is due to ultrasonic cavitation.

Rebound of plasma vancomycin levels after haemodialysis with highly permeable membranes.

Vancomycin is usually given only once a week to haemodialysis (HD) patients. If highly permeable dialysis membranes are used, however, high clearance values have been reported, so the aim of the study was to determine whether high clearance of vancomycin resulted in sufficient drug elimination to induce subtherapeutic plasma levels after one week. In 18 chronic HD patients, treated with polysulfone dialyzers (1.2 m2), the pharmacokinetics of vancomycin were studied after administration of 1 g. Concentrations were determined by fluorescence polarisation immunoassay. At a blood flow of 219 ml.min-1, HD clearance of vancomycin was 62.3 ml.min-1. Immediately after dialysis plasma concentrations were 38% lower than predialysis levels. However, marked rebound in the vancomycin level was observed 5 h later, resulting in plasma levels only 16% lower than prior to dialysis. 3 HD treatments in 1 week removed about one third of the initial dose. After one week 15 of 18 patients still had a therapeutic plasma level (greater than 4 micrograms.ml-1). In conclusion, polysulfone membranes show high clearance of vancomycin. However, transfer of drug from blood to dialysate appears to be faster than from tissues to blood. Because of a marked rebound in plasma level after treatment, therapeutic drug concentrations will still be present in most patients after one week.

特集：血液透析膜の最近の進歩 Ｈｉｇｈｌｙ ｐｅｒｍｅａｂｌｅ ｍｅｍｂｒａｎｅの溶質透過性の検討

A few highly permeable dialysis membranes have been developed so far to remove beta-2-microglobulin having a molecular weight of 11, 800 that was identified as a new form of amyloid protein from patients on long-term hemodialysis. The present study is to evaluate the solute permeability for low molecular weight proteins such as beta-2-microglobulin of the highly permeable dialysis membranes by varying technical methods.The membranes tested included conventional and highly permeable dialysis membranes made of regenerated cellulose, and also highly permeable dialysis membranes of polysulfone and polyacrylonitrile as a reference. Solute permeability was determined by 1) the Wilson-plot method, 2) the microanalysis method with radioisotope-labeled solutes and 3) the photometric measurement. Test solutes were vitamin B12 beta-2-microglobulin, cytochrome-C and myoglobin.The highly permeable dialysis membranes of regenerated cellulose had higher surface porosities and pore sizes calculated from solute and pure water permeabilities and water content data that were practically the same as synthetic polymer membranes. This demonstrates that advanced membrane preparation techniques are capable of forming great surface porosity and large pore size on regenerated cellulose dialysis membranes.The Wilson-plot method is incapable of determination of diffusive permeability without ultrafiltration. Continuous measurements of optical density of a test solution in a hollow with optical fibers are well suited for precise determination of solute permeability by diffusion.The removed amount of beta-2-microglobulin calculated from solute permeability data of the most highly permeable dialysis membranes may not exceed the generated amount of beta-2-microglobulin.

Structure and permeability of dialysis membranes sterilized by various methods.

Appropriate design of dialysis membranes requires correct values of structural parameters such as pore radius, surface porosity, water content and tortuosity. It is impossible, however, to find the pore radius of dialysis membranes using a mercury porosimeter or an electron microscope because the pores are only several tens of angstroms in radius. Consequently, diffusional and convectional procedures such as the Lw method that uses both pure water permeability and water content, the Lw and Pm method which uses both solute and pure water permeability, and the sigma method which uses the reflection coefficient, have been employed extensively to determine the pore radius of dialysis membranes. The structural parameters of symmetric membranes are determined from water content, solute and pure water permeability data based on the Lw and Pm method combined with the tortuous pore model we have proposed. Determination of the structural parameters of microfiltration membranes for plasma separation having huge pores by various methods is required to verify the method of characterizing dialysis membranes based on the tortuous pore model. A dyeing method is also suitable for characterizing dialysis membranes of regenerated cellulose. Pore model studies using permeability and water content data for sterilized and treated membranes facilitate optimal design of dialysis membranes for clinical applications.