Clinical Application of PES Membrane Dialyzer

Objective The dialysate membrane can be classified into acetate membrane and synthetic membrane,while the latter can be further divided into polysulfone,polyacrylonitrile,etc.Polyethersulfone membrane is high molecular membrane material with excellent biocompatibility,stable mechanical properties,high temperature and pressure resistance,and good cleaning performance,which has been applied for more than 10 years.This trial is to assess the safety and efficacy of hollow polysulfone membrane fiber dialyzer with pattern number Enttex^(TM)-16LF(E60)for hemodialysis in patients with acute or chronic renal failure due to multiple factors.Methods Totally 76 patients receiving maintenance hemodialysis were included in a two-site,random,open label,two-stage,positive crossover and non inferiority validation study.The clinical efficacy and safety of the test device were observed,which was a hollow fiber dialyzer produced by Guangzhou Enttex Medical Products Co.,Ltd.,with polyethersulfone membrane imported from Germany.It was a low flux dialyzer with the pattern number of EnttexTM-16LF(E60).Inclusion criteria:①patients with acute or chronic renal failure due to various reasons who needed hemodialysis;②18 to 80 years old,gender unlimited;③patients who received stable dialysis for more than 3 months,regular hemodialysis 3 times a week,4 h at each time,blood flow rate of 200~350ml/min;④using bicarbonate dialysate at a flow rate of 500ml/min;⑤patients with arteriovenous fistula or who received artificial blood vessel puncture dialysis;received anticoagulation by heparin or low molecular weight heparin.Exclusion criteria:①patients needing heparin free dialysis for severe anemia,tumor and active bleeding;②patients with severe cardiac(gradeⅢcardiac function),hepatic(severe hepatitis and cirrhosis)and pulmonary diseases(severe respiratory failure).Results Comparison of parameters,including the changes of Kt/V,general creatinine and urea clearance rates and URR(urea reduction rate)shows no statistical significance in differences between the two devices,indicating that the test and control devices can equally and effectively eliminate toxins including creatinine and urea,etc.PPP and MITTP results are consistent.Comparison of ultrafiltration rates between two groups of patients shows no statistical difference.PPP and MITTP results are consistent,indicating that both the test device and control device can effectively eliminate water.In MITTP,electrolytes including K^+,Na^+,Cl^-,Ca^2+,HCO3^-,etc.show no statistical significance in difference between the test and control devices before and after dialysis(P>0.05).After treating by using test and control devices,body weight,serum potassium and phos-phorus all significantly decrease(P<0.001);serum Ca^2+,PO2,PCO2and HCO3^-all significantly increase(P<0.001).These results indicate that both the test and control devices can effectively eliminate serum potassium and phosphorus,and eliminate excess water in body,maintain the balance between liquid and electrolytes in patients.PPP and MITTP results are consistent.Conclusion This clinical trial confirms that hollow polyethersulfone membrane fiber dialyzer can be safely and effectively used in hemodialysis therapy.

The Clinical Randomized Controlled Trial on the Safety and Efficacy of Polyethersulfone Membrane Dialyzer in the Maintenance of Hemodialysis Patients

Objective： To observe the safety and efficacy of polyethersulfone membrane dialyzer used by chronic renal failure patients in clinical maintenance hemodialysis （MHD）. Methods： From January to February 2009, 36 patients were recruited from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The experiment was approved by the ethnical committee of Xinhua Hospital and under permissions fronl patients. All the patients were randomized into polyethersulfone group （PES, n=18） and polysulfone group （PS, n=18）. Hemodialysis was given by using Fresenius 4008S capacity-controlled dialyser and ultra-purified bicarbonate dialysate, more than 3.5 h each time, three times per-week, followed by heparin anticoagulation for a week, three times totally. Changes in blood urea nitrogen （BUN）, serum creatinine （Set）, phosphate （p2＋）, hemoglobin and albumin levels were determined for the efficacy and safety evahlation. Results： The serum BUN, Set and p2＋ concentrations significantly reduced after hemodialysis with different dialyzers, and the decrease amplitude of two groups was equivalent（P〉0.05）. The clearance rate of the serum BUN and Scr had no significant difference among two groups（P〉O.05）. The clearance rate （ml/min） of the sermn P^2＋ was 144.57 ±27.83 v.s. 117.15 ±22.77 in two groups. The clearance rate of the serum p^2＋ in PES group was more than that in PS group, and the difference was significant between two groups （P=0.0001）. It was indicated that PES and PS membrane could efficiently eliminate serum mieromolecule solute in MHD patients, so PES membrane excelled PS membrane in eliminating serum p2＋. The hemodialysis safety index, for example serum hemoglobin, albumin and blood pressure, had no significant difference between the two groups before and after hemodialysis （P〉0.05）. Conclusion： The efficacy and safety of the PES hollow fiber membrane dialyzer is equivalent to that of the imported PS membrane dialyzer in hemodialysis for MHD patients. The PES membrane excels PS membrane in eliminating sermn p^2＋.

Mathematical Modeling of the Dynamic Exchange of Solutes in a Prototype Hemodialyzer

Hemodialysis (HD) is one type of procedure for eliminating toxic chemicals and infusing bicarbonate in patients with end-stage renal disease (ESRD). Research and development in the hemodialyzer industry have, hitherto, depended mostly on empirical evidence to optimize HD therapy. This is often costly and involves numerous clinical trials. Developing a comprehensive time-dependent mathematical model to examine the dynamic exchange of solutes (HCO-3 and pCO2), blood pH and H+ ions in a prototype hollow-fiber hemodialyzer is essential in optimizing future design and improvement. A comprehensive mathematical model which is represented by a coupled set of transport equations and delineates the blood and dialyzate compartments of the hemodialyzer, and includes bicarbonate-buffering reaction in the blood channel and bicarbonate replenishment mechanism in the dialysate, is used to describe the time-dependent bulk concentration and exit concentration of solutes, blood pH and H+ ions in the hollow-fiber prototype hemodialyzer. A numerical simulation of the model is used to test several time-dependent bulks and exit concentration profiles of solutes in the blood and dialyzate. Results obtained from the numerical solution of the model show the bulk and exit concentrations of solute at various distances along the blood and dialyzate channels at different times. This modeling exercise will also allow us in our next study to examine some physical mechanisms of the hemodialyzer.

Synergetic effect of dialyzer membrane and lipopolysaccharide on peripheral blood mononuclear cell cytokine production in uremic patients

To investigate the effect of lipopoly^saccharide(LPS) and dialyzer membrane on cytokine gene expression and protein production in uremic patients on continuous ambulatory peritoneal dialysis(CAPD) and regular hemodialysis(HD) Methods Interleukin 1β(IL 1β) and interleukin 1 receptor antagonist(IL 1Ra) produced by cultured peripheral blood mononuclear cells(PBMC) after exposure to cuprammonium(Cup) membrane, polysulfone(PS) membranes or endotoxin were detected using enzyme linked immunoabsorbent assay mRNA expression was determined simultaneously by in situ hybridiztion Results In the absence of endotoxin, a small amount of IL 1β and IL 1Ra was produced by PBMC harvested from HD and CAPD patients after incubation with Cup or PS during subsequent 24 hour culture For healthy controls, IL 1β was barely detectable just above the detection limit Although no differences could be found in protein synthesis between Cup and PS, in situ hybridization showed that Cup induced markedly higher level mRNA coding for IL 1β and IL 1Ra In contrast, when subsequently stimulated with endotoxin, PBMC incubated with Cup could produce significantly larger amount of IL 1β and IL 1Ra compared with either unstimulated cells or post incubation PBMC with PS LPS stimulated PBMC in healthy subjects produced similar amount of IL 1β and markedly lower IL 1Ra as compared with uremic patients on HD and CAPD Conclusions Two steps are required in healthy control for IL 1β and IL 1Ra production: induction of mRNA transcription by membrane contact, followed by LPS induced translation, while in uremic patients on HD or CAPD bioincompatibility membrane and LPS have a synergetic effect on IL 1β and IL 1Ra production There exists an unbalance between IL 1β and its specific inhibitor in maintenance dialysis patients

EXPERIMENT AND RESEARCH ON DEVELOPMENT AND CHARACTERIZATIONS OF ANODIC ALUMINA MEMBR-ANE FOR USE IN HEMODIALYSIS

Objective The correlation between various formative conditions and the pore characterizationsof the anodic alumina membrane is investigated to seek the optimal conditions for the formation of anodic aluminamembrane. Methods High purity aluminum foils are used as the starting materials. The anodization is conduc-ted in three types of electrolytes, 3% sulfuric acid, 5% sulfuric acid and 2. 7% oxalic acid, respectively, with dif-ferent voltages at for 48h. The characterizations of the pore size, the effective porosity and the pore porosity areobserved and determined by scanning electron microscopy. The hydraulic conductances of the membranes are meas-ured to confirm that the pores are open and evaluate the permselectivity of the membranes. Results The experi-mental result shows that the ordered pore arrays are obtained for oxidation under our experimental conditions. Withthe increasing of the voltage, the pore size and pore porosity increased significantly (P <0.05) , while the effectiveporosity decreased significantly (P <0.05) with the same electrolyte. The pore size formed in 3% sulfuric acid or5% sulfuric acid is much smaller than in 2. 7% oxalic acid as an electrolyte. The hydraulic conductance of anodicalumina membrane that formed under our experimental condition is higher than those of the membranes are availablecurrently used in clinical. Conclusion The results suggest that the optimal conditions for the formation of anodicalumina membrane that used in hemodialysis are in 3% or 5% sulfuric acid with 12. 5V to 17. 5V at for 48h.

Experimental Design and Clinical Observation of Modialysis Apparatus

Objective To evaluate the clinical safety and efficacy of polyethersulfone membrane hollow fiber dialyzer Enttex^(TM)-16LF(E60)in treating patients with end stage renal disease caused by a variety of reasons.Methods This clinical trialwas designed as a randomized,open,two-phase crossover and positive control,non-inferiority study.To evaluate the indicators of blood routine test,serum biochemical indexes,blood gas analysis,vital signsbefore and after hemodialysis,and the adverse events were recorded indetail.Results There was no significant difference in creatinine,urea,creatinine clearance and electrolytes between Enttex TM-16LF dialyzer and control dialyzer before and after hemodialysis,no adverse event associated with the Enttex^(TM)-16LF dialyzer was found during the study.Conclusions The Enttex^(TM)-16LF dialyzeris effective and safe for hemodialysis in patients with end stage renal disease.

The Adverse Event Profile in Patients Treated with Transferon^TM(Dialyzable Leukocyte Extracts): A Preliminary Report

Background: Dialyzable leukocyte extracts (DLE) are heterogeneous mixtures of peptides less than 10 kDa in size that are used as immunomodulatory adjuvants in immune-mediated diseases. TransferonTM is DLE manufactured by National Polytechnic Institute (IPN), and is registered by Mexican health-regulatory authorities as an immunomodulatory drug and commercialized nationally. The proposed mechanism of action of TransferonTM is induction of a Th1 immunoregulatory response. Despite that it is widely used, to date there are no reports of adverse events related to the clinical safety of human DLE or TransferonTM. Objective: To assess the safety of TransferonTM in a large group of patients exposed to DLE as adjuvant treatment. Methods: We included in this study 3844 patients from our Clinical Immunology Service at the Unit of External Services and Clinical Research (USEIC), IPN. Analysis was performed from January 2014 to November 2014, searching for clinical adverse events in patients with immune-mediated diseases and treated with TransferonTM as an adjuvant. Results: In this work we observed clinical nonserious adverse events (AE) in 1.9% of patients treated with TransferonTM (MD 1.9, IQR 1.7 - 2.0). AE were 2.8 times more frequently observed in female than in male patients. The most common AE were headache in 15.7%, followed by rash in 11.4%, increased disease-related symptomatology in 10%, rhinorrhea in 7.1%, cough in 5.7%, and fatigue in 5.7% of patients with AE. 63% of adverse event presentation occurred from day 1 to day 4 of treatment with TransferonTM, and mean time resolution of adverse events was 14 days. In 23 cases, the therapy was stopped because of adverse events and no serious adverse events were observed in this study. Conclusion: TransferonTM induced low frequency of nonserious adverse events during adjuvant treatment. Further monitoring is advisable for different age and disease groups of patients.