Polysulfone Dialyzers Research Articles

#2548 In vitro evaluation of proenkephalin kinetics in hemofiltration and hemodialysis

Abstract Background and Aims Proenkephalin A 119-159 (penKid) is a stable surrogate marker for enkephalins (endogenous opioids regulating kidney function). PenKid plasma concentration correlates to GFR and increases in AKI, for this reason it can be used for prediction and diagnosis of AKI (even subclinical forms) and need of RRT. Furthermore, it seems to be also a reliable biomarker to predict the successful liberation from RRT and may therefore aid in the successful weaning of patients from RRT. PenKid has the perk of maintaining stable its concentration during RRT, suggesting that is barely filtered, in contrast to other biomarkers. However, with its small size of 4.5 kDa, penKid can be assumed to be freely filtered through the glomerulus and dialysis membranes. To address the issue about stable penKid plasma concentrations in RRT (no extracorporeal removal or increased production in response to impaired kidney function), we planned ex vivo experiments simulating different conditions of RRT. The aim of this study is to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively. Method The lyophilized peptide was solved in 20 mM Dipotassium phosphate, 6 mM Disodium EDTA [pH 8], avoiding concentrations higher than 1 mg/mL. The compound was diluted in 50 mL of plasma to ensure homogeneous distribution. For each experimental modality, a batch of blood of 1000 mL with adjusted hematocrit at 30% and albumin concentration of 3 g% was utilized. Blood was spiked with lyophilized synthetic penKid to achieve two target concentrations of 150 and 500 pmol/L in CVVH and CVVHD modalities, respectively. Blood was adjusted for a volume of 1000 mL, maintained at 37° and continuously stirred during the experiments. CVVH was performed with blood flow (QB) = 150 mL/min and ultrafiltration rate (QUF) = 20 mL/min to reproduce a filtration fraction of 20%. The ultrafiltrate was reinfused in the venous line to maintain initial volume. This allowed to define convective clearance and solute sieving coefficient in pure convective mode. CVVHD was performed with QB = 150 mL/min and dialysate flow (QD) = 35 mL/min (Net QUF = 0 mL/min). This allowed the calculation of diffusive clearance. A polysulfone dialyzer (AV1000 FMC, Bad Homburg, Germany) was utilized. Samples were taken at 10, 30, 60 minutes from the initiation of the circulation, in both modalities. Results Initial penKid concentrations in blood corresponded to the desired targets in all the experiments. Sieving coefficients displayed values between 0.69 and 1.5 and they appear to remain stable over time (Fig. 1). Diffusive clearance displayed values between 35 and 15.7 mL/min. Values appear to present a slight decrease over time (Fig. 2). The observed variability can be attributed to several factors: difference in plasma protein interference in various moments of the experiments, difference in concentration of penKid in plasma water versus plasma or blood, variability in the sample measurements. Conclusion Significant removal of penKid can be obtained by extracorporeal therapies both in convection (CVVH) and diffusion (CVVHD). Further investigation is needed to assess if these findings are confirmed during in vivo treatments in which penKid kinetics is affected by generation, elimination and changes in distribution volume.

In vitro evaluation of the platelet adhesion and interferon-γ production capacity of mononuclear cells coming in contact with a hydrophilic polymer-embedded polysulfone dialyzer

BackgroundA polysulfone dialysis membrane containing both polyvinylpyrrolidone (PVP) and the novel hydrophilic polymer (NV polymer) has been developed in an attempt to modify the blood contact surface of the membrane. In the present study, we performed an in vitro evaluation of the NV polymer-embedded membrane (NV membrane), focusing on the adhesion of blood cells to the membrane and the interferon (IFN)-γ production capacity of peripheral blood mononuclear cells coming in contact with the membrane.MethodsTwo membranes, the NV membrane and the conventional membrane embedded with PVP alone (CX), were evaluated simultaneously by dividing the porcine blood obtained from the same animal into two portions. The blood cell adhesion to the membranes was evaluated by measuring the hemoglobin concentrations and lactate dehydrogenase (LDH) activities in the eluates extracted from the membranes. The IFN-γ production capacity in response to phytohemagglutinin stimulation of mononuclear cells coming in contact with either membrane was evaluated.ResultsBoth the hemoglobin concentration and LDH activity, corrected by excluding erythrocytes from the eluate, were about 25% lower in the eluate from the NV membrane than in the eluate from the CX membrane. The IFN-γ production capacity of the mononuclear cells coming in contact with dialysis membrane remained unchanged for the case of the NV membrane, while it decreased for the case of the CX membrane.ConclusionsA lower degree of adhesion of blood cells to the membrane and a lower degree of reduction in the IFN-γ production capacity of mononuclear cells coming in contact with the membrane were observed for the NV membrane, as compared with the PVP membrane, which may suggest improved biocompatibility of the NV membrane.

296 Severe Thrombocytopenia induced by Poly-sulfone dialyzer membrane use in hemodialysis

296 Severe Thrombocytopenia induced by Poly-sulfone dialyzer membrane use in hemodialysis

Complement-mediated dialysis reaction during regular hemodialysis treatment: a case report

BackgroundHemodialysis reactions (HDRs) are similar to complement activation-related pseudo allergy (CARPA), a hypersensitivity reaction that occurs when administering certain (nano)drugs intravenously. The pathomechanism of CARPA was described based on animal experiments. Typical CARPA-like dialysis reactions, which occur at the start of hemodialysis, have been reported using polysulfone dialyzers. However, to our knowledge, this is the first dialysis reaction that occurred towards the end of hemodialysis treatment.Case presentationThis report describes a 52-year-old Caucasian male patient who had been receiving chronic hemodialysis for 3 years and exhibited a CARPA reaction during his third hour of treatment. Upon activation of the microbubble alarm, the extracorporeal system recirculated for five minutes. Following reconnection, the patient exhibited a drop in systemic blood pressure, chest pain, and dyspnea after five minutes. Symptoms disappeared spontaneously after reducing the speed of the blood pump, placing the patient in a Trendelenburg position, and administering a bolus infusion from the dialysis machine. The remaining dialysis treatment was uneventful.ConclusionNumerous case reports about reactions occurring with modern high-efficiency polysulfone dialyzers have been published. However, due to changes in the material structure by the manufacturers, we have not encountered such cases lately. The recently reported increase in thromboxane-B2 and pulmonary arterial pressure and complement activation upon re-infusion of extracorporeal blood following dialysis may explain the reaction observed here.

Endothelial membrane mimetic coating modified dialyzer for hemocompatible and anticoagulant-free hemodialysis

Current hemodialysis requires a dilemmatic balance between under- and over-heparinization to prevent extracorporeal circuit clotting and bleeding complications. Here we report an endothelial membrane mimetic coating (EMMC) strategy to replace the systemic heparinization by enhancing the hemocompatibility and anticoagulation property of all the blood contacting surfaces. The EMMC is created by precoating of polydopamine, multi-point anchoring of a sulfobetaine and carboxyl side-chain copolymer (PSBC) and grafting of unfractionated heparin (UFH). The multi-point anchored PSBC layer forms an ultra-thin cell outer membrane zwitterion mimicking interface to enhance hemocompatibility, while the grafted UFH molecules mimic anticoagulant molecules attached on endothelial membrane to endow superior anticoagulation activity. Compared to a commercial polysulfone (PSf) dialysis membrane, the EMMC coated membrane can reduce protein adsorption, platelet adhesion and complement activation by 94.1 %, 98.9 % and 77 %, respectively. Meanwhile, anticoagulation properties, including clotting time, surface thrombus formation time and thrombin inactivation efficacy, are significantly improved compared to currently reported heparin coatings. More importantly, anticoagulant-free extracorporeal circulation using the EMMC modified PSf dialyzer circuit in a beagle dog model was performed smoothly for 2 h without any observable thrombus. Furthermore, main dialysis parameters of the modified hemodialyzer were not decreased. In conclusion, this highly hemocompatible and strong anticlotting endothelial membrane mimetic coating has great potential to replace the systemic heparinization in hemodialysis.

Bisphenol A and chlorinated derivatives of bisphenol A assessment in end stage renal disease patients: Impact of dialysis therapy

Patients with end stage kidney disease treated by dialysis (ESKDD) process dialysis sessions to remove molecules usually excreted by kidneys. However, dialysis therapy could also contribute to endocrine disruptors (ED) burden. Indeed, materials like dialyzer filters, ultrapure dialysate and replacement fluid could exposed ESKDD patients to Bisphenol A (BPA) and chlorinated derivatives of BPA (ClxBPAs). Thus, our aim was to compare BPA and ClxBPAs exposure between ESKDD patients, patients with stage 5 chronic kidney disease (CKD5) not dialyzed and healthy volunteers. Then we describe the impact of a single dialysis session, according to dialysis modalities (hemodialysis therapy (HD) versus online hemodiafiltration therapy (HDF)) and materials used with pre-post BPA and ClxBPAs concentrations. The plasma levels of BPA and four ClxBPAs, were assessed for 64 ESKDD patients in pre and post dialysis samples (32 treated by HD and 32 treated by HDF) in 36 CKD5 patients and in 24 healthy volunteers. BPA plasma concentrations were 22.5 times higher for ESKDD patients in pre-dialysis samples versus healthy volunteers (2.208 ± 5.525 ng/mL versus 0.098 ± 0.169 ng/mL) (p < 0.001). BPA plasma concentrations were 16 times higher for CKD5 patients versus healthy volunteers, but it was not significant (1.606 ± 3.230 ng/mL versus 0.098 ± 0.169 ng/mL) (p > 0.05). BPA plasma concentrations for ESKDD patients in pre-dialysis samples were 1.4 times higher versus CKD5 patients (2.208 ± 5.525 ng/mL versus 1.606 ± 3.230 ng/mL) (p < 0.001). For healthy volunteers, ClxBPAs were never detected, or quantified while for CKD5 and ESKDD patients one ClxBPAs at least has been detected or quantified in 14 patients (38.8%) and 24 patients (37.5%), respectively. Dialysis therapy was inefficient to remove BPA either for HD (1.983 ± 6.042 ng/mL in pre-dialysis versus 3.675 ± 8.445 ng/mL in post-dialysis) or HDF (2.434 ± 5.042 ng/mL in pre-dialysis versus 7.462 ± 15.960 ng/mL in post dialysis) regarding pre-post BPA concentrations (p > 0.05). The same result was observed regarding ClxBPA analysis. Presence of polysulfone in dialyzer fibers overexposed ESKDD patients to BPA in pre-dialysis samples with 3.054 ± 6.770 for ESKDD patients treated with a polysulfone dialyzer versus 0.708 ± 0.638 (p = 0.040) for ESKDD patients treated without a polysulfone dialyzer and to BPA in post-dialysis samples with 6.629 ± 13.932 for ESKDD patients treated with a polysulfone dialyzer versus 3.982 ± 11.004 (p = 0.018) for ESKDD patients treated without a polysulfone dialyzer. This work is to our knowledge the first to investigate, the impact of a dialysis session and materials used on BPA and ClxBPAs plasma concentrations and to compare these concentrations to those found in CKD5 patients and in healthy volunteers.

Kinetics of Glucoregulatory Peptide Hormones during Hemodialysis with Cellulose Triacetate and Polysulfone Dialyzers in Patients with Diabetes and End-Stage Kidney Disease.

The mechanisms behind reported decreases in plasma insulin and glucagon during hemodialysis (HD) are not clear. Here, we investigated these mechanisms during HD treatment and the characteristics of insulin and glucagon removal when using two super high-flux membranes. In an experimental study, clearance, adsorption rates, and reduction rates of insulin and glucagon were investigated when using cellulose triacetate (CTA) and polysulfone (PS) membranes in a closed circuit using bovine blood. In a clinical study, 20 diabetes patients with end-stage kidney disease who were stable on HD were randomly selected for two HD sessions with two different membranes. At 1 h after the initiation of HD, insulin and glucagon clearance were measured, and the reduction rates were also investigated. In the experimental study, the PS membrane showed significantly higher clearance, adsorption rates, and reduction rates of insulin and glucagon compared with the CTA membrane. Although glucagon was detected in the ultrafiltration fluids in both membranes, insulin was absent in the PS membrane. In the clinical study, both membranes showed significant reductions in plasma insulin and glucagon at each time point. The PS membrane showed significantly higher insulin clearance and reduction rates compared with the CTA membrane. The two membranes showed no significant difference in glucagon clearance, but the glucagon reduction rate was significantly higher with the PS membrane. Our findings show that HD with the two super high-flux membranes used removes significant amounts of glucoregulatory peptide hormones from plasma in patients with diabetes and end-stage kidney disease, potentially affecting their glucose metabolism.

#3798 A MULTICENTER CLINICAL STUDY OF CELLULOSE TRIACETATE MEMBRANES AND POLYSULFONE MEMBRANE DIALYZERS IN MAINTENANCE HEMODIALYSIS PATIENTS

Abstract Background and Aims With the continuous improvement of dialysis membrane materials, polysulfone (PS) has replaced traditional cellulose membranes with excellent biocompatibility and dominates the market applications. In our clinical work, we found that the allergic reaction disappeared after the application of cellulose triacetate (CTA) in patients who were allergic to PS. In this study, we compared the differences in biocompatibility and solute clearance of CTA and PS dialyzers during long-term dialysis treatment. Method In this study, a multicenter clinical study was conducted, and patients attending Fuxin Mining Bureau Hospital, Northeast International Hospital and Shenyang Medical College Affiliated Central Hospital receiving maintenance hemodialysis from April 2019 to April 2020 were selected as the study population. The patients were divided into a polysulfone membrane group (n = 10) and a cellulose triacetate membrane group (n = 13) based on whether they tolerated the polysulfone membrane dialyzer, and all patients in the CTA group had an allergic reaction to the polysulfone membrane dialyzer. The effects of the two membranes on White Blood Cell (WBC), platelet (PLT), Hemoglobin(Hb), Complement3(C3), Complement4(C4), Tumor Necrosis Factor-α (TNF-α), Interleukin-1 (IL-1), interleukin-6 (IL-6), hypersensitive C-reactive protein (hs CRP), IgE, serum phosphorus (P), creatinine (CR), blood urea nitrogen (BUN), parathyroid hormone (PTH) were compared before and after the single dialysis session and after 12 months of dialysis,and Urea removal rate (URR) and spKt /V were calculated. Results There were no statistically significant differences between the two groups in the comparison of basic information such as age, gender, dialysis age and primary disease. Before the application of CTA and PS dialyzer treatment, there was no statistically significant comparison between groups for all observed indicators. After application of CTA and PS single dialysis: (i) The difference between the 2 groups of β2-MG (Z = -2.039, P = 0.041) and TNF-α (Z = -2.491, 0.013) was statistically different. (ii) There were no statistically significant differences between two groups in the comparison of hematological system, such as WBC, PLT, HB; complement, such as C3, C4; inflammatory factors, such as: IL-1, IL-6, hs CRP, IgE; uremic toxins, such as: P, CR, BUN, PTH (P&amp;gt;0.05). After the 12th month of regular hemodialysis treatment with PS and CTA: (i) The differences between the 2 groups for P (Z = -2.096, P = 0.036), BUN (Z = -2.038, P = 0.042), and spKt/V (t = -2.147, P = 0.049) were statistically significant. (ii) The difference between the 2 groups after 12 months of dialysis P (t = 0.114, P = 0.041) and before dialysis was statistically different between groups, and the other indexes mentioned above were not statistically different. Conclusion After a single dialysis session, TNF-αin the PS group was elevated and the biocompatibility of CTA was better than PS. The CTA group had better clearance of β2-MG than PS, and spKt/V reached the standard. After long-term dialysis, the effect of CTA on inflammation and complement system was not different compared with PS, and there was no difference in biocompatibility between the two membranes. spKt/V in the CTA group reached the standard, and the clearance of BUN and P was better than that of PS.

Relation Between Oxidative Stress and Carotid Artery Atherosclerosis in Hemodyalisis Patients

Abstract Oxidative stress represents a significant risk factor for the accelerated development of atherosclerosis in a population of patients on regular hemodialysis. Oxidative stress induced by hemodialysis can be triggered with both the bioincompatibility of dialysis membrane and increased endotoxin concentration in a hemodialysis solution. The aim of this study was to investigate the correlation between the parameters of oxidative stress, microinflammation, nutrition, secondary hyperparathyroidism and carotid artery intima-media thickness in patients on regular hemodialysis.One hundred and twenty five patients treated with standard hemodialysis and on-line hemodiafiltration with "high-flux" polysulfone dialysis membrane were examined. The following parameters of oxidative stress were measured : index of lipid peroxidation - measured as TBARS, nitric oxide in the form of nitrite - NO2-, super oxide anion radical - O2- and hydrogen peroxide - H2O2, catalase, superoxide dismutase (SOD) and reduced glutathione activity. For statistical analysis of results, the following tests were used: the Kolmogorov-Smirnov test, the Spirman test and the Pearson correlation test. Oxidative stress affects atherosclerosis of the carotid arteries in patients treated with regular hemodialysis and online hemodiafiltration. There is a statistically significant positive correlation between H2O2 concentration and the thickness of the carotid arteries` intima-media. High statistically significant positive correlation was found between TBARS concentration and carotid arteries intima-media thickness, while a high statistically significant negative correlation was found between SOD activity and a carotid artery intima-media thickness. There is a statistically significant negative correlation between the serum albumin and prealbumin concentration and a carotid artery intima-media thickness. Oxidative stress may be a significant risk factor for the carotid artery atherosclerosis development in patients treated with regular hemodialysis.

Perfluorooctanesulfonate Can Cause Negative Bias in Creatinine Measurement in Hemodialysis Patients Using Polysulfone Dialysis Membranes.

Serum creatinine is an important clinical marker for renal clearance. However, two conventional methods (Jaffe and enzymatic) are prone to interferences with organic compounds as compared to the standard method (isotope dilution–liquid chromatography–mass spectrometry) and can cause a significant negative bias. Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two common perfluorochemicals (PFCs) that can easily be accumulated in humans. We aimed to verify whether this bias is the result of an accumulation of PFCs. The serum creatinine values of 124 hemodialysis patients were analyzed using the three methods. We also aimed to evaluate which biochemical parameters will influence the difference between the conventional methods and the standard method. We found that a significant underestimation occurred when using the conventional methods. Albumin is an independent factor associated with negative bias, but it loses this correlation after dialysis, likely due to the removal of protein-bound uremic toxins. PFOS can cause negative bias when using the enzymatic method. Furthermore, this linear correlation is more significant in patients who used polysulfone-based dialysis membranes, possibly due to the better clearance of other uremic toxins. The serum creatinine of uremic patients can be significantly underestimated when using conventional methods. PFCs, as well the type of dialysis membrane being used, can be influencing factors.

Vitamin E-coated dialyzer alleviates erythrocyte deformability dysfunction in patients with end-stage renal disease undergoing hemodialysis.

Patients with end-stage renal disease (ESRD) are characterized by augmented oxidative stress (OS) due to the imbalance between the generation of increased concentrations of oxidative molecules and decreased antioxidant capacity. Vitamin E-coated dialyzer membranes (VEMs) have previously been reported to alleviate the imbalance of redox metabolism in patients with ESRD undergoing hemodialysis (HD); however, their effect on the deformability of red blood cells (RBCs) remains unknown. In the present study, 48 patients with ESRD undergoing HD were enrolled and randomly assigned into two groups: HD with VEMs (VEM group; n=24) and HD with polysulfone dialyzer membranes (PM group; n=24), and another 24 healthy volunteers served as the control group. The present study investigated the morphological changes and deformability of RBCs in patients with ESRD and healthy volunteers. The concentration of serum vitamin E, the parameters of antioxidant stress and OS, and the degree of oxidative phosphorylation and clustering of anion exchanger 1 (Band 3) in RBCs were measured. The results obtained suggested that VEM treatment markedly ameliorated the abnormalities of RBC morphology and deformability in patients with ESRD undergoing HD. Mechanistic studies showed that VEM treatment led to a marked improvement in the concentration of serum vitamin E, which was positively associated with the restored antioxidant capacity, and decreased oxidative phosphorylation and clustering of Band 3 in RBCs of patients with ESRD undergoing HD. Taken together, the results of the present study have demonstrated that VEM treatment effectively restored the imbalance of redox metabolism, and improved the oxidative phosphorylation and clustering of Band 3 in RBCs of patients with ESRD undergoing HD via delivering vitamin E, which may alleviate the abnormal morphological and mechanical properties of RBCs. These findings are anticipated to be useful with respect to improving the nursing care and cure rate of patients with ESRD.

MO643: Haemoperfusion Combined with Standard Haemodialysis May Have a Beneficial Effect on Serum Beta-2 Microglobulin Levels in Chronic Haemodialysis Patients

Abstract BACKGROUND AND AIMS Standard haemodialysis (HD) with low-flux membranes does not provide adequate middle molecular weight (MMW) clearance of uraemic toxins [1] and on-line haemodiafiltration (OL-HDF) may not be easily applicable and cost effective in some centres. We investigated whether low-flux conventional HD combined with hemoperfusion (HP) may offer any benefit regarding serum beta-2 microglobulin (β2M) levels as a surrogate of middle molecules in patients haemodialyzed for many years and we compared the method-combination with OL-HDF. METHOD We studied 24 stable anuric patients during 6 months, under standard medical therapy, aged 69 years (46–90), M: F = 20:4, on chronic HD for 84 (65–286) months, who formed three groups: A (GrA), B (GrB) and C (GrC). Each group included 8 age- and HD vintage-matched patients respectively. In GrA patients, a type HA130 cartridge for HP was connected in parallel to the low-flux polysulfone dialyzer and this combination of standard HD with HP (HD + HP) was used once a week for the first month, once every 2 weeks for the second month and once a month for the next 4 months. GrB patients underwent only standard HD treatment with low-flux polysulfone membranes and GrC patients were treated with OL-HDF. In all three groups serum β2M levels were determined at months 0 (M0) and 6 (M6), before (pre-dialysis, preD) and after (post-dialysis, postD) the second weekly session. RESULTS Serum preD β2M levels ​​were similar in GrA and GrB at M0 (44.1 ± 8.6 versus 34.6 ± 16.2 mg/L; P = NS) and at M6 (46.1 ± 7.6 versus 41.1 ± 18.9 mg/L; P = NS). In GrC, preD-β2M values were lower compared with GrA at both M0 (31.1 ± 4.2 mg/L; P = .008) and M6 (33.8 ± 6.82 mg/L; P = .02). In GrC, serum postD-β2M levels ​​decreased significantly at both M0 (7.4 ± 1.9 mg/L; P &amp;lt; .001) and M6 (9.9 ± 3.8 mg/L; P&amp;lt;.001). The postD reduction was maintained, with no difference between M0 and M6. An improvement/decrease in β2M values ​was observed only in GrA between M0 and M6 (−5.8 ± 7.2 versus 1.8 ± 5mg/L; P = .03) but not in GBr. CONCLUSION OL-HDF is obviously the most effective method for elimination of MMW uraemic toxins and in particular β2M [2–3]. Interestingly, the combination HD + HP seems to be more effective than low-flux HD alone [4] and it could be useful for specific patient cases in daily clinical practice in order to prevent or delay the onset and deterioration of symptomatic amyloidosis. Possible result improvement with a more frequent use of HD + HP needs further investigation.

A pilot study comparing the efficiency of a novel asymmetric cellulose triacetate (ATA) dialyser membrane (Solacea-190H) to a standard high flux polysulfone dialyser membrane (FX-80) in the setting of extended hours haemodialysis.

AimTo compare small, middle and large‐middle molecule clearance; and expression of markers of inflammation, between Solacea‐190H (asymmetric cellulose triacetate [ATA]) and FX‐80 dialysers in long‐hour haemodialysis patients.MethodsThis pilot, randomized cross‐over trial recruited 10 home haemodialysis patients. The total study duration was 8 weeks, using each dialyser for 4 weeks. Removal of small (urea, phosphate, creatinine and indoxyl sulfate [IS]), middle and large‐middle molecules (beta‐2 microglobulin [β2M], albumin), markers of inflammation (interleukin‐6 [IL‐6], malondialdehyde‐modified low density lipoprotein [MDA‐LDL] and alpha‐1 microglobulin [α1M]), was evaluated in serum and dialysate samples.ResultsReduction ratios [RR] were calculated for variables at the fourth week of each dialyzer sequence and results expressed as difference in mean RR between dialyzers. There was no difference in clearance of small molecules, with difference in mean RR for urea −2.43 (95% CI ‐6.44, 1.57; p = .19), creatinine −1.82 (95% CI ‐5.50, 1.85; p = .28) and phosphate −2.61 (95% CI −12.45, 7.23; p = .55); clearance of middle and large‐middle molecules with difference in mean RR (range) for β2M 2.2 (95% CI −3.2, 7.7; p = .35), IS 1.8 (95% CI −9.5, 13; p = .72) and albumin −0.6 (95% CI −5.5, 4.2; p = .77). There was lack of induction of markers of inflammation, including IL‐6 15.2 (95% CI −31.9, 62.2; p = .47), MDA‐LDL −8.1 (95% CI ‐22.1, 5.8; p = .21) and α1M −3.50 (95% CI −29.2, 22.2; p = .76). Dialysate removal results were concurrent.ConclusionThis study showed no difference in clearance of small, middle and large‐middle molecules, nor expression of markers of inflammation between dialysers.

Replication of fouling in vitro in hollow fiber dialyzers by albumin immobilization.

For designing and evaluating the dialyzer and investigating the optimal therapeutic conditions, in vitro studies bring us many useful findings. In hemodialysis, however, the membrane fouling due to protein molecules reduces solute removal performance. Therefore, we investigated a method for replicating the fouling in dialyzers in aqueous experiments. After the albumin solution was circulated in the test circuit with a dialyzer, a glutaraldehyde solution was pumped into the dialyzer to immobilize albumin on the hollow fiber membrane. Under various immobilization conditions, the permeability of creatinine and vitamin B12 was evaluated by dialysis experiments. The creatinine clearance after immobilization of albumin was decreased, suggesting pore plugging by our fouling replication method. The glutaraldehyde crosslinked albumin molecules that adhered them to the membrane firmly. Moreover, the degree of fouling may be controlled by changing the concentration of albumin solution and the volume of glutaraldehyde solution used for immobilization. Our fouling replication method was applied to three types of polyester polymer alloy (PEPA) dialyzers and one polysulfone (PSf) dialyzer. This method enables to evaluate the permeability of various dialyzers with fouling in vitro that will be of great help in collecting data for designing dialyzers.

Impact of Intestinal Microbiota on Quality of Life (QoL) of Hemodialysis Patients

Chronic kidney disease is a global problem. Increasing evidence suggests that interstinal microflore is altered in patients with Chronic Kidney Disease (CKD).The gut microbiome is a key driver of chronic inflammation. Many of uremic retention solutes are produced by dysbiotic intestinal microflore that may have a great impact on survival of the CKD patients. Our sample study consisted of 147 patients (78 female, 69 male age 18-75) undergoing hemodialysis in one dialysis center. Data were collected by the completion of a scpecially designed questionnaire. Patients received hemodialysis therapy for 4-5 hours sessions, three times weekly using polysulfone dialyzers. It was revealed significant alteration of the colonic bacterial flora in hemodialysis patients, with the excess of the uremic toxin producing bacteria. Also, there was strict correlation between gut dysbiosis and HD patent's QoL.

Impact of Intestinal Microbiota on Quality of Life (QoL) of Hemodialysis Patients

Chronic kidney disease is a global problem. Increasing evidence suggests that interstinal microflore is altered in patients with Chronic Kidney Disease (CKD).The gut microbiome is a key driver of chronic inflammation. Many of uremic retention solutes are produced by dysbiotic intestinal microflore that may have a great impact on survival of the CKD patients. Our sample study consisted of 147 patients (78 female, 69 male age 18-75) undergoing hemodialysis in one dialysis center. Data were collected by the completion of a scpecially designed questionnaire. Patients received hemodialysis therapy for 4-5 hours sessions, three times weekly using polysulfone dialyzers. It was revealed significant alteration of the colonic bacterial flora in hemodialysis patients, with the excess of the uremic toxin producing bacteria. Also, there was strict correlation between gut dysbiosis and HD patent's QoL.

Clinical advantages of a newly launched anti-thrombotic PMMA membrane for the nutritional status and dialysis-related symptoms in older chronic dialysis patients: a multicenter pilot study

BackgroundMalnutrition that is associated with inflammation is a key factor of poor outcome in chronic hemodialysis patients, especially in older dialysis patients. Polymethyl methacrylate (PMMA) membrane has been reported to improve the inflammatory status by removing pro-inflammatory cytokines via adsorption. However, older dialysis patients occasionally have multiple uncomfortable dialysis-related symptoms, which decrease their quality of life and survival rate. We investigated whether a new PMMA membrane, Filtryzer NF, can improve malnutrition and dialysis-related symptoms in older hemodialysis patients.MethodsPatients over 70 years of age who were dialyzed using a polysulfone (PS) membrane were enrolled and randomly allocated into one of two groups: control or NF. In the NF group, the PS dialyzers were changed to NF, whereas in the control group, the PS membrane was continuously used. The primary outcome was the malnutrition–inflammation score (MIS). Secondary outcomes were C-reactive protein, normalized protein catabolism rate, percent of creatinine generation rate, arm circumference, and eight dialysis-related symptoms. The primary and secondary outcomes were measured every 3 months for 1 year.ResultsFifty-four hemodialysis patients were randomly assigned to the NF group (n = 28) or the control group (n = 26). During the 12-month study period, 11 and 10 patients were withdrawn from the NF and control groups, respectively. There was no significant difference in the MIS between the groups during the study or between the beginning and the end of the study within each group. For the secondary outcomes, there was a significant reduction in the total score of dialysis-related symptoms in the NF group but not in the control group. During the study period, the total dialysis-related symptoms score in the NF group was significantly decreased from 6 (range, 1–16) to 3 (range, 0–11) (median [minimum–maximum], p < 0.05). Other secondary outcomes were not different between the groups or between the beginning and the end of the study.ConclusionsThis study showed no advantage for the nutritional status in older hemodialysis patients using NF compared with PS. However, our results indicated that NF may improve several dialysis-related symptoms. To clarify this clinical finding, large-scale prospective randomized clinical trials are required.Trial registrationThis study was registered with the Clinical Trials Registry of the University Hospital Medical Information Network (registration ID, UMIN000032990).

Performance and Hemocompatibility of a Novel Polysulfone Dialyzer: A Randomized Controlled Trial.

High-flux dialyzers effectively remove uremic toxins, are hemocompatible to minimize intradialytic humoral and cellular stimulation, and have long-term effects on patient outcomes. A new dialyzer with a modified membrane surface has been tested for performance and hemocompatibility. This multicenter, prospective, randomized, crossover study involved the application of the new polysulfone-based FX CorAL 600 (Fresenius Medical Care, Bad Homburg, Germany), the polyarylethersulfone-based Polyflux 170H (Baxter Healthcare Corporation, Deerfield, IL), and the cellulose triacetate-based SureFlux 17UX (Nipro Medical Europe, Mechelen, Belgium), for 1 week each, to assess the noninferiority of the FX CorAL 600's removal rate of β2-microglobulin. Performance was assessed by removal rate and clearance of small- and medium-sized molecules. Hemocompatibility was assessed through markers of complement, cell activation, contact activation, and coagulation. Of 70 patients, 58 composed the intention-to-treat population. The FX CorAL 600's removal rate of β2-microglobulin was noninferior to both comparators (P<0.001 versus SureFlux 17UX; P=0.0006 versus Polyflux 170H), and superior to the SureFlux 17UX. The activation of C3a and C5a with FX CorAL 600 was significantly lower 15 minutes after treatment start than with SureFlux 17UX. The activation of sC5b-9 with FX CorAL 600 was significantly lower over the whole treatment than with SureFlux 17UX, and lower after 60 minutes than with the Polyflux 170H. The treatments with FX CorAL 600 were well tolerated. FX CorAL 600 efficiently removed small- and medium-sized molecules, showed a favorable hemocompatibility profile, and was associated with a low frequency of adverse events in this study, with a limited patient number and follow-up time. Further studies, with longer observation times, are warranted to provide further evidence supporting the use of the new dialyzer in a wide range of therapeutic options, and for long-term treatment of patients on hemodialysis, to minimize the potential effects on inflammatory processes.

MO666INVESTIGATIONS INTO DIFFERENCES AND SIMILARITIES BETWEEN SHORT DAILY HIGH-FLUX HEMODIALYSIS AND SHORT DAILY ON-LINE HEMODIAFILTRATION

Abstract Background and Aims Short daily hemodialysis (SDHD) has improved outcomes observed in conventional thrice-weekly hemodialysis (CHD). Analogously, short daily hemodiafiltration (SDHDF) has also improved outcomes observed in conventional thrice-weekly hemodiafiltration (CHDF). Furthermore, while high-volume CHDF has been proclaimed to be superior to CHD, there have been no studies comparing SDHDF to SDHD. We performed a comparison of clinical, laboratory, echocardiographic and quality of life features in dialysis patients treated by SDHD or SDHDF. Method Twelve patients (mean age 60.8±15.4 years; 7 males; AVF 7, AVG 1, Catheter 4) on regular in-center SDHD program were studied in a longitudinal, prospective, non-randomized, single-subject A-B-A design comparing high-flux SDHD to post-dilution on-line SDHDF. Patients had been for at least 6 months on SDHD (105-150min, 6x/week; SDHD1) and were clinically stable before conversion to SDHDF (105-150min, 6x/week, mean total convective volume of 63.57±5.44 L per week) for 6 months. Following that, all patients were switched back to SDHD for another 6 months (SDHD2). Data were collected at the end of each period. Dialysis parameters throughout the study were matched and set as follows: high-flux polysulfone dialyzers (BBraun Xevonta Hi 23®), blood flow 300–350 mL/min, dialysate flow 500 mL/min and ultra-purified water (Aquaboss heat disinfection osmosis). The results were expressed as mean ± standard deviation. Each patient served as his/her own control. Repeated measures analysis of variance (ANOVA) were used. Results Slightly higher predialysis mean arterial pressure (MAP) levels were observed during SDHDF (102.51±11.28 mmHg) compared to SDHD1 (MAP 95.5±9.82 mmHg, p&amp;lt;0.01) or to SDHD2 (97.61±11.19 mmHg, p=0.03), without significant differences in intradialytic blood pressure variability. Similarly, there was an increase in predialysis hemoglobin levels (Hb) during SDHDF (Hb 12.39±1.2 g/dL), compared to SDHD1 (Hb 11.30±1.09 g/dL, p=0.02) or to SDHD2 (Hb 11.23±1.84 g/dL, p&amp;lt;0.01), although there were no significant differences in erythropoietin-stimulating agent or iron supplementation weekly doses, transferrin saturation rates or ferritin levels. Solute kinetics measurements showed higher myoglobin clearance during SDHDF (45.95±11.0 mL/min) compared to SDHD1 (20.11±5.2 mL/min, p&amp;lt;0.01) or to SDHD2 (21.39±3.55 mL/min, p&amp;lt;0.01). Likewise, there was a slight increase in β2-microglobulin removal in SDHDF (64.92±10.4 mL/min) compared to SDHD1 (59.78±17.0 mL/min, p&amp;lt;0.01) or to SDHD1 (53.01±7.71 mL/min, p&amp;lt;0.01), whereas there were no significant differences in urea and creatinine clearances. On the other hand, predialysis osteometabolic (serum PTH, calcium, phosphate, alkaline phosphatase, sodium, potassium, glucose and glycated hemoglobin), inflammatory (serum c-reactive protein and interleukin-6) or nutritional (serum albumin, total protein and lipid profile) parameters did not change significantly during the study. Left ventricular mass index, left atrial volume index and global longitudinal strain, assessed by echocardiography at the end of all 3 periods, were similar, as well as brain natriuretic peptide and homocysteine serum levels. Additionally, there were no significant changes in any quality of life features evaluated by Kidney Disease Quality of Life-Short Form, or symptoms assessed by Edmonton Symptom Assessment System Revised Renal, throughout the full course of the study. Conclusion In spite of mild increase of predialysis mean arterial pressure and hemoglobin levels along with greater removal of middle molecular weight solutes, no others clinical, laboratory, echocardiographic or quality of life findings differed significantly during the three periods. Together, these data do not provide evidence of clinically meaningful benefit from on-line hemodiafiltration over high-flux hemodialysis, both performed six times a week.

MO387CLINICAL PERFORMANCE, HEMOCOMPATIBILITY AND SAFETY OF A NEW DIALYZER WITH A MODIFIED POLYSULFONE MEMBRANE

Abstract Background and Aims Hemodialyzers containing membranes made from a blend of polysulfone and polyvinylpyrrolidone (PVP) are widely used. PVP makes the membrane material more hydrophilic to reduce interactions with plasma proteins and platelets. A modified spinning technique has been established to stabilize the PVP on the blood-side surface in the polysulfone dialysis membrane in the new dialyzer FX CorAL 600. The objective of the present study was to prove for this new dialyzer non-inferiority of performance in comparison to established dialyzers. Further, hemocompatibility and safety of the dialyzers were explored. Method In a multicenter, prospective, randomized, crossover study adult patients on online hemodiafiltration (HDF) were enrolled. They were treated for one week each with on-line HDF in post-dilution mode, and in randomized order with the dialyzers FX CorAL 600, FX 600, and FX CorDiax 600 (all Fresenius Medical Care, Bad Homburg, Germany). Blood samples were taken on the midweek session before start, at the end to analyze removal rate and at 60 min to determine clearance of ß2-microglobulin, myoglobin, urea, creatinine and phosphate. Further a pattern of hemocompatibility parameters and safety was evaluated. Assuming no carry over effect, linear mixed models were used for statistical analysis. Results The mean age of the 49 enrolled patients was 66.3±13.6 years, 76% were male. Treatments were performed in post-dilution mode with a mean blood flow &amp;gt; 300 mL/min and a substitution volume &amp;gt;19 L. The removal rate of ß2-microglobulin was 74.4, 70.4, and 73.1% for the FX CorAL 600, FX 600, and FX CorDiax 600 dialyzer, respectively. FX CorAL 600 proved to be statistically significantly non-inferior to FX 600 (p=0.0006) and to FX CorDiax 600 (p=0.036). The removal rate of FX CorAL 600 was by 4.0% (confidence interval 0.4 – 7.5%) significantly higher than with FX 600. The difference to FX CorDiax 600 was not significant. The clearance of ß2-microglobulin and myoglobin and the removal rate of myoglobin were significantly higher with the new dialyzer FX CorAL 600 than with the FX 600, and comparable to the FX CorDiax 600. Performance for small molecules was similar for all dialyzers. The complement factors C3a and C5a increased early in the treatment with a peak at 15 min, without differences between the three dialyzers for C3a, and for C5a with significantly lower increase at 15 min with FX CorAL 600 than for FX 600 (p=0.007); the difference of increase between FX CorAL 600 and FX CorDiax 600 was not significant (p=0.515). The course of sC5b9 was similar for all three dialyzers, with significantly lower increase at 15 min for both FX CorAL 600 (p=0.009) and FX CorDiax 600 (p=0.026) as compared to FX 600 and similar increase at 60 min for both FX CorAL 600 (p=0.573) and FX CorDiax 600 (p=0.386) as compared to FX 600. The area-under-the-curve for the course of sC5b-9 with FX CorAL 600 was significantly lower than with FX 600 (p=0.044) and comparable to FX CorDiax 600 (p=0.092). The leukocyte count showed a decrease in the first 15 min of the treatment, which recovered afterwards, similarly for all treatment phases with the different dialyzers. Further, the dialyzers did not differ with respect to adverse events. Conclusion All three dialyzers showed good performance, with higher removal rates for middle molecules with the new dialyzer FX CorAL 600 compared to the FX 600. Hemocompatibility profiles were mostly similar, with lower activation of C5a and of sC5b9 with FX CorAL 600 compared to FX 600. The new dialyzer provides comparable performance levels capable of delivering adequate treatment and good tolerability for the patient.