Polymethylmethacrylate Membrane Research Articles

Exploration of Daptomycin Adsorption by Polymethylmethacrylate Hemofilter In Vitro.

Blood purification therapy with cytokine-adsorbing hemofilters has been used to treat sepsis-associated hypercytokinemia. Polymethylmethacrylate (PMMA) hemofilters are frequently used for this purpose; however, adsorption and removal of teicoplanin, a therapeutic agent, have been reported. Similar concerns have been shared regarding daptomycin because its structure resembles that of teicoplanin; nevertheless, there have been no reported effects associated with daptomycin in this context. We studied the adsorption of daptomycin onto a PMMA hemofilter in vitro and investigated its adsorption onto hollow fiber membranes by adding cut PMMA membranes to a daptomycin solution. Additionally, the daptomycin solution was circulated in a dialysis circuit connected to a PMMA hemofilter, and changes in daptomycin content were examined. The daptomycin content decreased immediately after adding the hollow fiber membranes, similar to that observed for teicoplanin. The daptomycin content was lower than that of the standard reagent in the dialysis circuit model, reaching values below the measurement limit after 20 min. These results suggested that daptomycin was adsorbed and removed by the PMMA hemofilter. Encountering this effect during clinical use is plausible; therefore, daptomycin administration via a PMMA hemofilter should be avoided during blood purification therapy.

Contribution of Adsorption and Hematocrit Levels to Ganciclovir Clearance in an in Vitro Continuous Hemodiafiltration Model.

Estimation of the continuous hemodiafiltration (CHDF) clearance (CLCHDF) of ganciclovir (GCV) is crucial for achieving efficient treatment outcomes. Here, we aimed to clarify the contribution of diafiltration, adsorption, and hematocrit level to the CLCHDF of GCV in an in vitro CHDF model using three membranes: polyacrylonitrile and sodium methallyl sulfonate copolymer coated with polyethylenimine (AN69ST); polymethylmethacrylate (PMMA); and polysulfone (PS). In vitro CHDF was performed with effluent flow rates (Qe) of 800, 1500, and 3000 mL/h. The initial GCV concentration was 10 µg/mL while that of human serum albumin (HSA) was 0 or 5 g/dL. The CLCHDF, diafiltration rates, and adsorption rates were calculated. The whole blood-to-plasma ratio (R) of GCV for a hematocrit of 0.1 to 0.5 was determined using blood samples with 0.5 to 100 µg/mL of GCV. The in vitro CHDF experiment using AN69ST, PMMA, and PS membranes showed that the total CLCHDF values were almost the same as the Qe and not influenced by the HSA concentration. The diafiltration rate exceeded 88.1 ± 2.8% while the adsorption rate was lower than 9.4 ± 9.4% in all conditions. The R value was 1.89 ± 0.11 and was similar at all hematocrit levels and GCV concentrations. In conclusion, diafiltration mainly contributes to the CLCHDF of GCV, rather than adsorption. Hematocrit levels might not affect the relationship between the plasma and blood CLCHDF of GCV, and the CLCHDF of GCV can be estimated from the Qe and R, at least in vitro.

Fast Fabrication Nanopores on a PMMA Membrane by a Local High Electric Field Controlled Breakdown.

The sensitivity and accuracy of nanopore sensors are severely hindered by the high noise associated with solid-state nanopores. To mitigate this issue, the deposition of organic polymer materials onto silicon nitride (SiNx) membranes has been effective in obtaining low-noise measurements. Nonetheless, the fabrication of nanopores sub-10 nm on thin polymer membranes remains a significant challenge. This work proposes a method for fabricating nanopores on polymethyl methacrylate (PMMA) membrane by the local high electrical field controlled breakdown, exploring the impact of voltage and current on the breakdown of PMMA membranes and discussing the mechanism underlying the breakdown voltage and current during the formation of nanopores. By improving the electric field application method, transient high electric fields that are one-seven times higher than the breakdown electric field can be utilized to fabricate nanopores. A comparative analysis was performed on the current noise levels of nanopores in PMMA-SiNx composite membranes and SiNx nanopores with a 5 nm diameter. The results demonstrated that the fast fabrication of nanopores on PMMA-SiNx membranes exhibited reduced current noise compared to SiNx nanopores. This finding provides evidence supporting the feasibility of utilizing this technology for efficiently fabricating low-noise nanopores on polymer composite membranes.

Development and application of a 3D image analysis strategy for focused ion beam - Scanning electron microscopy tomography of porous soft materials.

In recent years, the potential of porous soft materials in various device technologies has increased in importance due to applications in fields, such as wearable electronics, medicine, and transient devices. However, understanding the 3-dimensional architecture of porous soft materials at the microscale remains a challenge. Herein, we present a method to structurally analyze soft materials using Focused Ion Beam - Scanning Electron Microscopy (FIB-SEM) tomography. Two materials, polymethyl methacrylate (PMMA) membrane and pine wood veneer were chosen as test-cases. FIB-SEM was successfully used to reconstruct the true topography of these materials in 3D. Structural and physical properties were subsequently deduced from the rendered 3D models. The methodology used segmentation, coupled with optimized thresholding, image processing, and reconstruction protocols. The 3D models generated pore size distribution, pore inter-connectivity, tortuosity, thickness, and curvature data. It was shown that FIB-SEM tomography provides both an informative and visual depiction of structure. To evaluate and validate the FIB-SEM reconstructions, porous properties were generated from the physical property analysis techniques, gas adsorption analysis using Brunauer-Emmett-Teller (BET) surface area analysis and mercury intrusion porosimetry (MIP) analysis. In general, the data obtained from the FIB-SEM reconstructions was well-matched with the physical data. RESEARCH HIGHLIGHTS: Porous specimens of both synthetic and biological nature, a poly(methyl methacrylate) membrane and a pine veneer respectively, are reconstructed via FIB-SEM tomography without resin-embedding. Different thresholding and reconstruction methods are explored whereby shadowing artifacts are present with the aid of free open-source software. Reconstruction data is compared to physical data: MIP, gas adsorption isotherms which are analyzed via BET and Barrett-Joyner-Halenda (BJH) analysis to yield a full picture of the materials.

Comparative analyses of adsorbed circulating proteins in the PMMA and PES hemodiafilters in patients on predilution online hemodiafiltration.

Acute and chronic inflammation are common in patients with end-stage kidney disease (ESKD). So, the adsorption of pro-inflammatory cytokines by the hollow fiber of the dialysis membrane has been expected to modify the inflammatory dysregulation in ESKD patients. However, it remains to be determined in detail what molecules of fiber materials can preferably adsorb proteins from the circulating circuit. We aimed this study to analyze directly the adsorbed proteins in the polymethyl methacrylate (PMMA) and polyethersulfone (PES) membranes in patients on predilution online hemodiafiltration (OL-HDF). To compare the adsorbed proteins in the PMMA and PES hemodiafilters membrane, we initially performed predilution OL-HDF using the PES (MFX-25Seco) membrane while then switched to the PMMA (PMF™-A) membrane under the same condition in three patients. We extracted proteins from the collected hemodiafilters by extraction, then SDS-PAGE of the extracted sample, protein isolation, in-gel tryptic digestion, and nano-LC MS/MS analyses. The concentrations of adsorbed proteins from the PMMA and PES membrane extracts were 35.6±7.9 μg/μL and 26.1±9.2 μg/μL. SDS-PAGE analysis revealed distinct variations of adsorbed proteins mainly in the molecular weight between 10 to 25 kDa. By tryptic gel digestion and mass spectrometric analysis, the PMMA membrane exhibited higher adsorptions of β2 microglobulin, dermcidin, retinol-binding protein-4, and lambda-1 light chain than those from the PES membrane. In contrast, amyloid A-1 protein was adsorbed more potently in the PES membrane. Western blot analyses revealed that the PMMA membrane adsorbed interleukin-6 (IL-6) approximately 5 to 118 times compared to the PES membrane. These findings suggest that PMMA-based OL-HDF therapy may be useful in controlling inflammatory status in ESKD patients.

Poor removal of tedizolid during continuous hemodiafiltration: experiments using an in vitro continuous hemodiafiltration model.

Tedizolid is an oxazolidinone anti-MRSA drug with included in the National Health Insurance Drug Price List in 2018. The effect of hemodialysis on tedizolid phosphate concentrations has been reported; pre-dialysis concentrations decreased by 10% compared to post- dialysis concentrations. However, the material of the dialysis membrane remains unknown. In addition, there have been no reports on the effects of continuous hemodiafiltration. In this study, we investigated the effects of continuous hemodiafiltration on tedizolid using two types of dialysis membranes made of different materials. The adsorption of tedizolid, linezolid, and vancomycin to two different dialysis membranes was investigated, and the clearance of each drug was calculated by experiments using an in vitro continuous hemodiafiltration model. The adsorption of tedizolid, linezolid, and vancomycin on the dialysis membranes was examined, and no adsorption was observed. Experimental results from the continuous hemodiafiltration model showed that linezolid and vancomycin concentrations decreased over time: after two hours, the respective decreases were 26.48 ± 7.14% and 28.51 ± 2.32% for polysulfone membranes, respectively. The decrease was 23.57 ± 4.95% and 28.73 ± 5.13% for the polymethylmethacrylate membranes, respectively. These results suggested that linezolid and vancomycin were eliminated by continuous hemodiafiltration. In contrast, tedizolid phosphate and tedizolid concentrations decreased slightly in the polysulfone and polymethylmethacrylate membranes. The decrease in concentrations were 2.10 ± 0.77% and 2.97 ± 0.60% for the polysulfone membranes, respectively. For the polymethylmethacrylate membranes, the decrease in concentration were 2.01 ± 0.88% and 1.73 ± 0.27%, respectively. These results suggested that tedizolid should not be considered for dose control during continuous hemodiafiltration.

Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study

Introduction: The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α₁-Microglobulin (α₁-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α₁-m and β₂-microglobulin (β₂-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in comparison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study. Methods: Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α₁-m, β₂-m, small molecules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment. Results: Clearance rates of α₁-m at 60 min were −2.8 ± 5.2 mL/min with Pre-PS, −0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α₁-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of β₂-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS. Conclusion: The removal rate of α₁-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed β₂-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effectively removes α₁-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.

Efficacy of polymethylmethacrylate membrane hemodiafilter Filtryzer® PMF™-21A in improving pruritus in hemodialysis patients: a prospective interventional study

BackgroundHemodialysis-associated pruritus (HAP) occurs in 60–80% of hemodialysis patients. This significant complication not only decreases quality of life through sleep disturbance and depression, but also leads to poor survival outcomes. The polymethylmethacrylate (PMMA) membrane was the first synthetic polymer membrane for the hollow-fiber artificial kidney created in 1977. PMMA membrane dialyzers have been reported to be effective for improving various complaints, including pruritus, and nutritional status. In Japan, a PMMA membrane hemodiafilter Filtryzer® PMF™-A (PMF-A) was launched in November 2021 and subsequently became available for online hemodiafiltration (OHDF). This study aimed to determine whether PMF-A effectively improves pruritus in hemodialysis patients.MethodsParticipants were 20 patients (median age 74.5 years) on predilution OHDF (pre-OHDF) or postdilution OHDF (post-OHDF) using an Asymmetric Triacetate Membrane® hemodiafilter (FIX-210E eco or FIX-210S eco), who were experiencing pruritus of “very mild” or higher severity based on the Shiratori severity score either during the daytime or nighttime. After switching to post-OHDF with PMF-21A (substitution flow rate: 10 L/session), the substitution flow rate was gradually increased according to results of pruritus evaluation every 2 weeks over 3 months. The primary endpoint was the severity of pruritus evaluated using visual analogue scale (VAS) and the Shiratori severity score. Secondary endpoints included white blood cell count (WBC), hemoglobin level (Hb), platelet count (Plt), serum albumin level (Alb), high-sensitivity C-reactive protein (hsCRP), IL-6, dry weight (DW), and solute removal performance.ResultsThe median VAS score was significantly decreased 2 weeks after switching compared with baseline (44 mm) and remained significantly decreased at Week 12 (22 mm; p < 0.01). From baseline to Week 12, 16 patients (80%) showed improvement in VAS score. The percentage of patients with mild to moderate daytime pruritus according to the Shiratori severity score decreased significantly from 80.0% to 45.0% (p < 0.05), whereas no significant change was observed for nighttime pruritus (p = 0.267). Pre-dialysis serum β2-MG levels were significantly higher at Week 12 compared with baseline. No significant changes were observed in WBC, Hb, Plt, serum Alb, hsCRP, IL-6, or DW.ConclusionsOHDF with PMF-21A may be more effective in improving HAP.

Comparison of the cytokine adsorption ability in continuous renal replacement therapy using polyethyleneimine-coated polyacrylonitrile (AN69ST) or polymethylmethacrylate (PMMA) hemofilters: a pilot single-center open-label randomized control trial

BackgroundSepsis occurs as a result of dysregulated host response to infection. However, cytokine adsorption therapy may restore the balance of proinflammatory and anti-inflammatory mediator responses in patients with sepsis. This study aimed to determine the cytokine adsorption ability of two different types of continuous renal replacement therapy (CRRT) hemofilters for polyethyleneimine-coated polyacrylonitrile (AN69ST) (surface-treated) and polymethylmethacrylate (PMMA) CRRT.MethodsWe performed a randomized controlled trial among sepsis patients undergoing CRRT, who were randomly assigned (1:1) to receive either AN69ST or PMMA-CRRT. The primary outcome was cytokine clearance of hemofilter adsorption (CHA). The secondary endpoints were the intensive care unit (ICU) and 28-day mortalities.ResultsWe randomly selected 52 patients. Primary outcome data were available for 26 patients each in the AN69ST-CRRT and PMMA-CRRT arms. The CHA of high-mobility group box 1, tumor necrosis factor, interleukin (IL)-8, monokine induced by interferon-γ, and macrophage inflammatory protein were significantly higher in the AN69ST-CRRT group than in the PMMA-CRRT group (P < 0.001, P < 0.01, P < 0.001, P < 0.001 and P < 0.001, respectively). In contrast, the CHA of IL-6 was significantly higher in the PMMA-CRRT group than in the AN69ST-CRRT group (P < 0.001). In addition, the 28-day mortality was not significantly different between the two groups (50% in AN69ST-CRRT vs. 30.8% in PMMA-CRRT, P = 0.26).ConclusionAN69ST and PMMA membranes have different cytokine CHA in patients with sepsis. Therefore, these two hemofilters may have to be used depending on the target cytokine.Trial registration number: This study was registered in the University Hospital Medical Information Network on November 1, 2017 (Trial No: UMIN000029450, https://center6.umin.ac.jp).

Evaluation of the Effect of the PMMA Dialysis Membrane on the Level of Inflammation in Patients on Hemodialysis

Introduction: The inflammation syndrome is typical for chronic kidney disease (CKD) and increases with the progression of CKD. It is extremely important to monitor the markers of inflammation in patients with CKD, as there is a clear relationship between the level of inflammation and mortality in these patients. Currently, there is no single approach to the treatment of chronic inflammation in patients with CKD. Methods: This was a prospective open cohort study. We studied 31 patients on hemodialysis from March 1, 2020, to August 1, 2021, in 2 Moscow clinics (No. 7 and S.P. Botkin). Inclusion criteria for patients in the study were an adequate dialysis according to the KT/V index ≥1.4, absence of an active inflammatory process or infections, age over 18 years, standard hemodialysis regimen of 3 times per week, at least 4 h, levels of interleukin-6 (IL-6), IL-8, and C-reactive protein (CRP) above the reference values. Patients were transferred from hemodialysis performed using a standard polysulfone (PS) membrane to a polymethylmethacrylate (PMMA) membrane (Filtryzer BK-2.1F). For dialysis treatment in patients, blood flow rates of 250–350 mL/min were used, and the flow rate of the dialysis solution was set at 500 mL/min. The control group consisted of 19 patients, with similar inclusion parameters, who continued their treatment with hemodialysis using a PS membrane. The aim of the research was to study the effect of the dialysis membrane (Filtryzer BK-2.1F) on the level of inflammation in routine practice compared to a PS membrane. Adverse events were monitored. Results: By the end of the study, after 12 months, the levels of cytokines significantly decreased only in patients who had treatment with PMMA membrane, starting from the 3rd month of treatment, and became close to normal levels: IL-6 from 16.9 ± 8.0 to 8.5 ± 4.8 pg/mL (p ≤ 0.0001); IL-8 from 78.5 ± 11.4 to 43.6 ± 11.6 pg/mL (p ≤ 0.0001); and CRP from 10.33 ± 2.83 to 6.15 ± 1.57 mg/L (p ≤ 0.0001). Values of inflammation markers did not change in control group. Conclusion: In our study, we demonstrated for the first time a significant reduction in the level of inflammation in patients on standard hemodialysis in routine practice due to the use of PMMA membranes.

Examination of the Effect of Switching Dialysis Membranes on the Immune Response to Influenza Virus Vaccination in Hemodialysis Patients

Introduction: In this study, we examined the effect of switching dialysis membranes on the response to influenza virus vaccination in HD patients. Methods: This study consisted of two phases. In phase 1, antibody titers were measured and compared between HD patients and healthy volunteers (HVs) before and after vaccination against influenza virus. Using antibody titers 4 weeks after vaccination, HD patients and HVs were classified according to seroconversion (i.e., antibody titers against all four strains were >20-fold) or non-seroconversion (i.e., antibody titer against at least one strain was <20-fold). In the phase 2, we examined whether the change in the dialysis membrane from a polysulfone (PS) to a polymethyl methacrylate (PMMA) membrane affected the response to vaccination in HD patients without seroconversion in response to the vaccine the previous year. Patients with seroconversion and non-seroconversion were classified as responders and nonresponders, respectively. Additionally, we compared clinical data. Results: In the phase 1, 110 HD patients and 80 HVs were enrolled, and their seroconversion rates were 58.6% and 72.5%, respectively. In the phase 2, 20 HD patients without seroconversion in response to the vaccine the previous year were enrolled, and the dialyzer membrane was changed to PMMA 5 months before annual vaccination. After annual vaccination, 5 and 15 HD patients were categorized as responders and nonresponders, respectively. In the responders, β2-microglobulin, white blood cell counts, platelet counts, and serum albumin levels (Alb) were all higher than in the nonresponders. Conclusion: The responsiveness to vaccination against influenza virus was lower in HD patients compared with HVs. Changing the dialysis membrane from PS to PMMA appeared to affect the response to vaccination in HD patients.

Protein-Bound Uremic Toxins and Inflammation Process in Hemodialysis Patients: Is There a Role for Adsorption Hemodiafiltration?

Introduction: Despite major advances in the field of dialysis, there are still some unmet needs such as reducing inflammation through adequate depuration. It is well known that the wide spectrum of pro-inflammatory and pro-atherosclerotic uremic toxins are inefficiently removed by current dialysis techniques. Adsorption seems to be an extra tool to remove toxins, but its effect and optimization have not been widely studied. The aim of this report was to present preliminary results regarding the possibility of performing hemodiafiltration with a highly adsorptive polymethylmethacrylate membrane. Methods: The study was first conducted in 10 patients in which the safety and feasibility of hemodiafiltration with PMMA BG-U 2.1 membrane were tested through measurement of hemolysis indices, transmembrane pressures, and dialysis adequacy. Twenty patients were prospectively observed for 18-month period in which they consecutively underwent standard hemodialysis, standard post-dilution hemodiafiltration, and polymethylmethacrylate-based post-dilution hemodiafiltration. Protein-bound uremic toxins concentrations and inflammatory markers were measured throughout the observed period. Results: HDF-PMMA was inferior to HDF in convective volume, but KT/V was similar, and no differences were noted in operating pressures during the two treatments. During HDF-PMMA period of treatment, we observed a significant reduction of CPR levels, and HDF-PMMA was superior to all other treatments in hepcidin removal even if this did not significantly affect hemoglobin levels. HDF-PMMA could significantly reduce indoxyl sulfate (indoxyl) concentration over a period of 6 months but not for p-cresyl sulfate (p-cresyl). Conclusion: PMMA BG-U 2.1 membrane can be safely and efficiently used in hemodiafiltration. Moreover, as these preliminary results show, adding adsorption properties to convection and diffusion enabled an increased removal of indoxyl uremic toxin associated to a reduction in inflammation markers as CRP and hepcidin without any negative impact on albumin levels.

In vitro analysis of factors affecting the continuous hemodiafiltration clearance of teicoplanin.

In the treatment of sepsis, continuous hemodiafiltration (CHDF) and the administration of antibiotics such as teicoplanin (TEIC) are frequently performed in parallel. We aimed to clarify the factors influencing the CHDF clearance (CLCHDF ) of TEIC using a polymethylmethacrylate (PMMA) membrane or a polyacrylonitrile and sodium methallyl sulfonate copolymer membrane coated with polyethylenimine (AN69ST). We also investigated whether the adsorption of TEIC onto the hemofilters inhibits the adsorption of interleukin (IL)-6 onto the membranes. TEIC, human serum albumin (HSA), and IL-6 were incubated with pieces of hemofilter membranes and adsorption rates were calculated. The CLCHDF , diafiltration rate, and adsorption rate of TEIC were calculated using an in vitro CHDF circuit model. The adsorption rates of TEIC onto the pieces of PMMA and AN69ST membranes ranged from 15.0% to 100% and from -10% to 5%, respectively. The adsorption rate of IL-6 was similar with or without TEIC. The CLCHDF and adsorption rate of TEIC under PMMA-CHDF depended on HSA, but not on effluent flow rate (Qe). The CLCHDF under AN69ST-CHDF depended on HSA and Qe. The observed CLCHDF under AN69ST-CHDF was similar to the predicted value (the product of Qe and the plasma unbound fraction). The observed CLCHDF under PMMA-CHDF was 2.0-7.8 times greater than the predicted value. Adsorption mainly contributes to the CLCHDF of TEIC using PMMA membranes, whereas diafiltration mainly contributes to the CLCHDF of TEIC using AN69ST membranes. TEIC adsorption might not affect the adsorption of IL-6 onto PMMA membrane.

A Larger Membrane Area Increases Cytokine Removal in Polymethyl Methacrylate Hemofilters.

Blood purification is performed to control cytokines in critically ill patients. The relationship between the clearance (CL) and the membrane area during adsorption is not clear. We hypothesized that the CL increases with the hydrophobic area when hydrophobic binding contributes to cytokine adsorption. We investigated the relationship between the hemofilter membrane area and the CL of the high mobility group box 1 protein (HMGB-1) and interleukin-6 (IL-6). We performed experimental hemofiltration in vitro using polymethyl methacrylate membranes CH-1.8W (1.8 m2) and CH-1.0N (1.0 m2), as well as polysulfone membrane NV-18X (1.8 m2). After adding 100 mg of HMGB1 or 10 μg of IL-6 into the test solution, experimental hemofiltration was conducted for 360 min in a closed-loop circulation system, and the same amount of HMGB1 and IL-6 was added after 180 min. With CH-1.8W and CH-1.0N, both HMGB-1 and IL-6 showed a rapid concentration decrease of more than 70% at 180 min and 360 min after the re-addition. At 15 min, the CL of HMGB-1 was CH-1.8W: 28.4 and CH-1.0N: 19.8, and that of IL-6 was CH-1.8W: 41.1 and CH-1.0N: 25.4. CH-1.8W and CH-1.0N removed HMGB1 and IL-6 by adsorption and CH-1.8W was superior in CL, which increased with a greater membrane area.

Clinical efficacy of blood purification using a polymethylmethacrylate hemofilter for the treatment of severe acute pancreatitis.

BackgroundSevere acute pancreatitis (SAP) is a systemic inflammatory disease, and it can often complicate into acute kidney injury (AKI) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study aimed to evaluate the clinical effectiveness of blood purification using a polymethylmethacrylate (PMMA) hemofilter.MethodsWe retrospectively examined 54 patients, who were diagnosed with SAP according to the Japanese criteria from January 2011 to December 2019.ResultsOf a total of 54 SAP patients, 26 patients progressively developed AKI and required continuous hemodialysis with a PMMA membrane hemofilter (PMMA-CHD). Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were significantly higher in patients requiring PMMA-CHD than in patients not requiring hemodialysis. The lung injury scores were also significantly higher in patients requiring PMMA-CHD. Of the 26 patients, 16 patients developed ALI/ARDS and required mechanical ventilation. A total of seven patients developed severe ALI/ARDS and received additional intermittent hemodiafiltration using a PMMA hemofilter (PMMA-HDF). Although the length of intensive care unit stay was significantly longer in patients with severe ALI/ARDS, blood purification therapy was discontinued in all the patients. The survival rates at the time of discharge were 92.3% and 92.9% in patients with and without PMMA-CHD, respectively. These real mortality ratios were obviously lower than the estimated mortality ratios predicted by APACHE II scores.ConclusionsThese finding suggest that the blood purification using a PMMA hemofilter would be effective for the treatment of AKI and ALI/ARDS in SAP patients.

MO272: Effect of the Hollow Fiber Diameter and Membrane Surface Area of the Polymethyl Methacrylate Membrane Filter Used in Continuous Renal Replacement Therapy on the Lifetime of the Filter

Abstract BACKGROUND AND AIMS When polymethyl methacrylate (PMMA) membranes are used in renal replacement therapy, inflammatory cytokines and other substances are removed by adsorption. However, these filters are also prone to clogging and the filter lifetimes are likely to be short. In the present study, we investigated the effects of the hollow fiber inner diameter and membrane area of PMMA membranes on the filter lifetime and protein removal performance using an in vitro continuous hemofiltration (CHF) experimental model with porcine blood. METHOD Three filters with different hollow fiber inner diameters and membrane areas were used: CH-1.0N (membrane area, 1.0 m2; hollow fiber inner diameter, 200 µm), CH-1.0W (prototype: 1.0 m2; 240 µm), and CH-1.8W (1.8 m2; 240 µm). Blood samples from one pig were divided into three portions, and in vitro CHF experiments for each filter were performed at QB = 100 mL/min and QS = QF = 10 mL/min. The pressure changes, total protein concentration in the blood, and total protein amount in the filtrate were measured during the experiments. From the results of the pressure changes, the time for the TMP to reach 200 mmHg (corresponding to the time when the membrane pores were clogged) and the time for the pressure drop through the filter to reach 200 mmHg (corresponding to the time when the hollow fibers were clogged) were calculated as the filter lifetime for comparative evaluation. RESULTS The time for the TMP to reach 200 mmHg was significantly longer with CH-1.8W than that with CH-1.0N or CH-1.0W (Friedman test, P &amp;lt; .05, n = 15). The time for the pressure drop through the filter to reach 200 mmHg was significantly longer with CH-1.8W than that with CH-1.0N or CH-1.0W (Friedman test, P &amp;lt; 0.05, n = 15). The results suggest that an increased membrane surface area is an essential factor for extending the filter lifetime. The total protein adsorption was significantly higher for the CH-1.0W and CH-1.8W filters than for the CH-1.0N filter (two-way ANOVA and post hoc Tukey test, P &amp;lt; 0.01, n = 15). Thus, the membranes with larger hollow fiber inner diameters (CH-1.8W and CH-1.0W) adsorbed more protein. CONCLUSION A larger membrane area contributes to a longer filter lifetime, whereas increase in the hollow fiber inner diameter does not. On the other hand, the protein removal performance, especially the adsorption performance, was higher for membranes with larger hollow fiber inner diameters.

Committee report: Questionnaire survey on the treatment of COVID-19 in patients receiving dialysis therapy

BackgroundPatients with coronavirus disease 2019 (COVID-19) who receive dialysis therapy develop more severe disease and have a poorer prognosis than patients who do not. Although various data on the treatment of patients not receiving dialysis therapy have been reported, clinical practice for patients on dialysis is challenging as data is limited. The Infection Control Committee of the Japanese Society for Dialysis Therapy decided to clarify the status of treatment in COVID-19 patients on dialysis.MethodsA questionnaire survey of 105 centers that had treated at least five COVID-19 patients on dialysis was conducted in August 2021.ResultsSixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities.ConclusionsOur survey revealed a variety of treatment practices in each facility. Further evidence and innovations are required to improve the prognosis of patients with COVID-19 receiving dialysis therapy.

A Comparative Assessment of Human Serum Proteins Interactions with Hemodialysis Clinical Membranes using Molecular Dynamics Simulation

AbstractEnd stage renal disease (ESRD) affects ≈10% of the world's population. Hemodialysis (HD) is a life‐sustaining extracorporeal blood purifying treatment for ESRD patients. Despite the advances in technology, the hemoincompatibility of the dialyzers leads to a high morbidity and mortality rate. Decreasing interactions between polymers and blood constituents will result in controlled binding of human serum proteins to the surface and consequently enhanced biocompatibility. This study aims to assess the interaction energy between common hemodialysis polymer structures and human serum proteins using molecular dynamics simulation to offer a framework for understanding the dominant interactions as a reference for material development. Molecular dynamics and molecular docking simulations are conducted for calculating polymerprotein binding energies. Common serum proteins are selected for protein models. Poly aryl ether sulfone (PAES) with and without polyvinyl pyrrolidone (PVP), polyvinylidene fluoride (PVDF), cellulose triacetate (CTA), polyacrylonitrile (PAN), and polymethyl methacrylate (PMMA) membrane structures are chosen as the different classes of dialyzers. The van der Waals interactions between polymers and proteins dominate the binding energies sequence. Molecular docking results of the affinity between protein receptors‐ligands are aligned with the MD binding interaction.

New polymethylmethacrylate membrane, NF-U, improves nutritional status and reduces patient-reported symptoms in older dialysis patients

IntroductionWe previously reported the nutritional advantage of polymethylmethacrylate (PMMA) membranes to prevent the progression of malnutrition in dialysis patients. In this study, we examined whether a new PMMA dialyzer, NF-U, has advantages to improve the nutritional condition, patient-reported symptoms, and other clinical parameters in older dialysis patients.MethodsWe selected ten older chronic dialysis patients who were treated with NF-U for improving their worsening nutritional parameters and retrospectively evaluated nutrition and patient-reported symptoms. Patient-reported symptoms were surveyed by our original questionnaire including 20 items of symptom.ResultsSerum albumin concentration, geriatric nutritional risk index, and percent creatinine generation rate increased from 3.01 ± 0.16 to 3.25 ± 0.17 g/dL, 87.7 ± 5.8 to 91.4 ± 6.2, 100.2 ± 21.6 to 111.9 ± 20.9% at 1 and 4 months after switching to NF-U, respectively. For patient-reported outcomes, fatigue and the total score of patient-reported outcomes were improved after switching to NF-U.ConclusionOur results suggest that NF-U is a good choice for older dialysis patients to ameliorate their nutritional status and patient-reported outcomes.

Comprehensive analysis of cytokine adsorption properties of polymethyl methacrylate (PMMA) membrane material

In acute kidney injury caused by sepsis (septic AKI), excessive production of inflammatory mediators is believed to be involved in deterioration of the disease. Renal replacement therapy using a polymethyl methacrylate (PMMA) membrane hemofilter improves the pathological condition of septic AKI by adsorbing and removing inflammatory cytokines. However, the adsorption properties of the PMMA membrane are unclear. In this study, we comprehensively analyzed the adsorption of 48 different cytokines in human plasma to PMMA and polysulfone (PS) membranes. Seventy-nine percent (38/48) of the cytokines were adsorbed more efficiently to the PMMA membrane than the PS membrane, which indicates that the PMMA membrane has high cytokine adsorption ability. The adsorption rate tended to be higher for the cytokines with lower molecular weight, and there was a significant correlation between the molecular weight of the cytokines and the adsorption rates. Electron microscopy showed that the PMMA hollow fiber membrane had a uniform internal structure from the inner to the outer layers of the membrane and had nano-pores inside the membrane that may have contributed to the adsorption of proteins with a specific molecular weight range. The clinical efficacy of a PMMA membrane hemofilter with cytokine adsorption properties against septic AKI needs further investigation including the evaluation of filtration performance of the hemofilters.