Ultrafiltration Coefficient Research Articles

On the Temporal Evolution of Key Hemofilter Parameters-In Vitro Study under Co-Current Flow.

Effective permeability KP, the ultrafiltration coefficient (KUF), the sieving coefficient (SC), and the loss/permeation of proteins (primarily albumin) are key parameters/specifications characterizing hemofilter (HF) performance. However, there are uncertainties regarding their determination. This work aims (a) to demonstrate that the co-current flow (of blood and dialysate) can lead to beneficial unidirectional filtration (from blood/plasma to dialysate) under a fairly uniform local trans-membrane pressure (TMP), unlike the presently employed counter-current flow; (b) to study the temporal evolution of key HF performance parameters under co-current flow, particularly during the important early stage of hemocatharsis (HC). Experiments with human plasma and BSA solutions in co-current flow mode (for which a fluid mechanical model is developed) show a fairly uniform local/axial TMP, which also improves the local/axial uniformity of protein membrane fouling, particularly under (currently favored) high convective flux operation. Due to incipient membrane fouling, a significant temporal variability/decline in the effective KP is observed, and, in turn, of other parameters (i.e., the Kuf, SC, and permeation/mass flux Mm for albumin and total proteins). A satisfactory correlation of the albumin/protein mass flux Mm with permeability KP is obtained, indicating strong inter-dependence. In conclusion, co-current flow, allowing for a fair local TMP axial uniformity, enables the acquisition of accurate/representative data on the evolution of HF parameters, facilitating their interpretation and correlation. The new results provide a basis for exploring the clinical application of the co-current flow.

#780 “In vivo” difference in ultrafiltration coefficient between two same membrane dialyzers: bigger surface area accounts for better dialysis outcomes?

Abstract Background and Aims Ultrafiltration coefficient (KUF) is a measure of dialyzer permeability to water, given by manufacturers, and expressed in milliliters/hour/mmHg of pressure gradient. Most dialyzers used at this moment are classified as high-flow as having a KUF >20 mL/h/mmHg. KUF value of a dialyzer is an “in vitro” measure which does not correlate with “in vivo” measure, stated to be 5-30% less than theoretical KUF. According to this statement, we wanted to study differences between theoretical and real KUF of two dialyzers with the same membrane composition and different surface area. For this task, we chose 2 dialyzers of usual use in our dialysis unit: FX CorDiax 1000 and FX CorDiax 80 (®FMC). These dialyzers have a main difference in Surface area: 2.3 and 1.8 m2, respectively, and have a theoretical KUF of 76 and 64 mL/h/mmHg. Also, both dialyzers differ in intern diameter (210 vs 185 µm). Method A prospective, not randomized trial was conducted. Inclusion criteria were patients in chronic dialysis at our center, in postdilutional online hemodiafiltration with a FX1000 dialyzer. All patients were informed and accepted freely signing an informed consentment. On 2 consecutive weeks, the intermediate dialysis session of the week was performed in a DBB-EXA dialysis monitor (®Nikkiso), first with a FX CorDiax 1000 and next week with a FX CorDiax 80, with habitual patient dialysis parameters (240 minutes). Blood tests were taken previous and after the session to evaluate clearance differences between both filters. During the session, pressure and flow data was recorded, with an “in vivo” KUF measurement given by the monitor. Results Dialysis sessions were performed in 12 patients who met inclusion criteria. Data results are shown in Table 1. Significant differences between FX CorDiax 1000 and FX CorDiax 80 were observed in prefilter pressure (p 0.008), convective volume (p 0.034), prolactin reduction ratio (p 0.012), “in vivo” KUF/ “in vitro” KUF ratio (p 0.002). “In vivo” KUF graphic given by the monitor showed a logarithmic function curve, with a stabilization between the 2nd and 3rd hour of the session. Conclusion In our study, measurement of “in vivo” KUF by Nikkiso monitor showed a slow decrease after 2nd hour of session, probably related with protein cake of membrane pores. “In vivo” KUF measure was approximately a 40-45% of theoretical value given by manufacturer. The “in vivo” KUF/ “in vitro” KUF ratio was higher for the smaller dialyzer, which probably means a higher optimization of its surface area with usual dialysis sessions. Convective volume and prolactin reduction ratio, as parameters of dialysis efficacy, are higher in the dialyzer with higher surface area and inner intern diameter.

Influence of utilizing hemodialysis membranes outside-in on solute clearance and filtration efficiency – One step towards a novel combined lung and kidney support device

Many membrane oxygenator patients suffer from renal disfunction. For these patients, a novel device integrating artificial lung and kidney support is being developed. Although outside-in blood flow is standard for membrane oxygenators, this is not typical for hemodialysis systems. The effect of outside-in blood flow on the efficiency of hemodialysis fibers for continuous hemodialysis and hemofiltration is yet unclear.This study evaluates the efficiency of commercial hemodialyzer membranes utilized outside-in compared to traditional inside-out mode regarding clearance of urea and creatinine, and ultrafiltration coefficient during in-vitro tests with porcine blood. Our results showed that dialyzers (1.2 m2, asymmetric hollow fibers) utilized outside-in had similar clearances of urea and creatinine compared to dialyzers used in the traditional mode (p > 0.7). However, outside-in dialyzers had an ultrafiltration coefficient four times lower than dialyzers applied in a conventional way, but adequate fluid removal could be achieved by controlling pressures in the system. This in-vitro study indicates that outside-in fibers could be sufficiently effective to maintain typical continuous renal replacement therapy doses. We regard this as one step towards a novel device with a mixed membrane fiber bundle utilizing blood flow outside both hemodialysis fibers and gas exchange fibers to provide simultaneous lung and kidney support.

Responses in Blood Pressure and Kidney Function to Soluble Guanylyl Cyclase Stimulation or Activation in Normal and Diabetic Rats

Introduction: Agonists of soluble guanylate cyclase (sGC) are being developed as treatment for cardiovascular disease. Most effects of nitric oxide (NO) on glomerular and tubular function are mediated through sGC, but whether sGC agonists mimic these effects is unknown. Methods: Renal clearance and micropuncture studies were performed in Wistar-Froemter rats (WF), with or without streptozotocin diabetes (STZ-WF), and in Goto-Kakizaki rats (GK) with mild type 2 diabetes to test for acute effects of the sGC “stimulator” BAY 41-2272, which synergizes with endogenous NO, and the “activator” runcaciguat, which generates cGMP independent of NO. Results: Both sGC agonists reduced arterial blood pressure (MAP). For MAP reductions <10%, the drugs increased GFR in WF and STZ-WF but not in GK. Larger MAP reductions outweighed this effect and GFR declined, with better preserved GFR in STZ-WF. Changes in GFR could not be accounted for by changes in RBF, suggesting parallel changes in ultrafiltration pressure and/or ultrafiltration coefficient. The doses chosen for micropuncture in WF and GK reduced MAP by 2–10%, and the net effect on single nephron GFR and ultrafiltration pressure was neutral. The effects of the drugs on tubular reabsorption were dominated by declining MAP, and no natriuretic effect was observed at any dose. Discussion/Conclusion: sGC agonists impact kidney function directly and because they reduce MAP. The direct tendency to increase GFR is most apparent for MAP reductions <10%. The direct effect is otherwise subtle and overridden when MAP declines more. Effects of sGC agonists on tubular reabsorption are dominated by the effects on MAP.

MO654: Automatic KUF Max Determination as a Tool to Prescribe a Personalized Convection Flow in Post-Dilution Haemodiafiltration by Predicting the Transmembrane Pressure to Which the System will be Subjected

Abstract BACKGROUND AND AIM Post-dilutional haemodiafiltration (HDF) with high convection volumes are suggested to improve survival. However, a large increase in convection flow (QUF) is associated with high transmembrane pressure (TMP) which, when exceeding limits advised by guidelines, acts as a limiting factor and prevents achieving the prescription. Our aim is to predict the TMP needed to reach any given convection flow for a patient and dialysis session. METHOD The TMP necessary to obtain a desired convection was predicted from the automatic determination of the maximum ultrafiltration coefficient (KUF max, HDF machine Dialog iQ, BBraun, Melsungen, Germany) and compared to the actual value for 16 patients and 29 dialysis sessions. KUF max was determined at the start of the session and the coefficients of the quadratic regression of the ultrafiltration coefficient (KUF) on convection flow (KUF = a*(QUF)² + b* QUF + c) were obtained and used to predict the TMP needed to obtain a convection of 30% of QB (QUF max), knowing that TMP = QUF/KUF. Then, infusion rate was set at QUF max and the observed TMP was recorded after 8 minutes stabilization. Dialyses were performed with the patient's usual dialyzer (Diacap pro for 28 sessions, Nephral 400 for 1 session) and blood flow [363 ± 30 mL/min (300–400 mL/min)]. Observed and estimated TMPs were compared. RESULTS There was a high correlation between both TMPs (Pearson's R = 0.98; P &amp;lt; .01). The Bland and Altman analysis showed an average difference (systematic bias) of 3.3% with 95% limits of agreement of −9 and +15% and a maximal difference of 12%, indicating a slight overestimation. CONCLUSION KUF max determination allows estimating TMP at any QUF prescription with an acceptable error (3%). Therefore, the KUF on QUF parabolic curve may be of help in the clinical setting to prescribe the most suitable convection in post-dilutional HDF by predicting the TMP the filtrating system will be submitted to. Based on this principle, automatic systems to aid personalized convection flow prescriptions can be developed.

Flummoxed by flux: the indeterminate principles of haemodialysis.

ABSTRACTIn haemodialysis (HD), unwanted substances (uraemic retention solutes or ‘uraemic toxins’) that accumulate in uraemia are removed from blood by transport across the semipermeable membrane. Like all membrane separation processes, the transport requires driving forces to facilitate the transfer of molecules across the membrane. The magnitude of the transport is quantified by the phenomenon of ‘flux’, a finite parameter defined as the volume of fluid (or permeate) transferred per unit area of membrane surface per unit time. In HD, as transmembrane pressure is applied to facilitate fluid flow or flux across the membrane to enhance solute removal, flux is defined by the ultrafiltration coefficient (KUF; mL/h/mmHg) reflecting the hydraulic permeability of the membrane. However, in HD, the designation of flux has come to be used in a much broader sense and the term is commonly used interchangeably and erroneously with other measures of membrane separation processes, resulting in considerable confusion. Increased flux is perceived to reflect more ‘porous’ membranes having ‘larger’ pores, even though other membrane and therapy attributes determine the magnitude of flux achieved during HD. Adjectival designations of flux (low-, mid-, high-, super-, ultra-) have found indiscriminate usage in the scientific literature to qualify a parameter that influences clinical decision making and prescription of therapy modalities (low-flux or high-flux HD). Over the years the concept and definition of flux has undergone arbitrary and periodic adjustment and redefinition by authors in publications, regulatory bodies (US Food and Drug Administration) and professional association guidelines (European Renal Association, Kidney Disease Outcomes Quality Initiative), with little consensus. Industry has stretched the boundaries of flux to derive marketing advantages, justify increased reimbursement or contrive new classes of therapy modalities when in fact flux is just one of several specifications that determine membrane or dialyser performance. Membranes considered as high-flux previously are today at the lower end of the flux spectrum. Further, additional parameters unrelated to the rate of diffusive or convective transport (flux) are used in conjunction with or in place of KUF to allude to flux: clearance (mL/min, e.g. of β2-microglobulin) or sieving coefficients (dimensionless). Considering that clinical trials in nephrology, designed to make therapy recommendations and guide policy with economic repercussions, are based on the parameter flux they merit clarification—by regulatory authorities and scientists alike—to avoid further misappropriation.

Immobilizing chitosan nanoparticles in polysulfone ultrafiltration hollow fibre membranes for improving uremic toxins removal

In this study, the transport properties, and uremic toxins removal capability by polysulfone (PSF) membrane have been improved through the immobilisation of chitosan nanoparticles (CNP). Different loadings of CNP in the range of 0.1–0.5 wt% was incorporated into the polymer dope solutions to fabricate hollow fibre membranes that spun at different air-gap. The physicochemical study, pure water flux and uremic toxins analysis were employed to characterize the fabricated membranes physical and morphological characteristics. The incorporation of CNP increased PSF HFM porosity, pore size, ultrafiltration coefficient, KUF and uremic toxins clearance due to the formation of a thinner selective inner skin layer. However, the membranes spun with greater air-gap length exhibited decreased KUF and uremic toxins clearances due to increased membrane thickness and decreased porosity. The PSF membrane incorporated with 0.3 wt% CNP and spun at 50 cm air-gap demonstrated the highest KUF of 116 ml/m2.h.mmHg, BSA rejection of 91% as well as excellent uremic toxins clearances of 85%, 67% and 49% for urea, creatinine and lysozyme, respectively. These results suggested that the spinning conditions play critical roles in dictating the properties of the nanocomposite hollow fibre membrane (HFM) and the PSF/CNP HFM holds vast potential as a promising material for haemodialysis application.

Biodegradation Process of PSF-PUR Blend Hollow Fiber Membranes Using Escherichia coli Bacteria-Evaluation of Changes in Properties and Porosity.

This work was focused on biodegradation with Escherichia coli bacteria studies of PSF-PUR blend semipermeable hollow fiber membranes that possibly can undergo a partial degradation process. Hollow fiber membranes were obtained from polysulfone (PSF) and polyurethane (PUR) containing ester bonds in the polymer chain in various weight ratios using two solvents: N,N-Dimethylmethanamide (DMF) or N-Methylpyrrolidone (NMP). The membranes that underwent the biodegradation process were tested for changes in the ultrafiltration coefficient (UFC), retention and cut-off point. Moreover, the membranes were subjected to scanning electron microscopy (SEM), MeMoExplorerTM Software and Fourier-transform infrared spectroscopy (FT-IR) analysis. The influence of E. coli and its metabolites has been proven by the increase in UFC after biodegradation and changes in the selectivity and porosity of individual membranes after the biodegradation process.

Safety of a Novel Dialyzer Containing a Fluorinated Polyurethane Surface-Modifying Macromolecule in Patients with End-Stage Kidney Disease

Background: By inhibiting the adsorption of protein and platelets, surface-modifying macromolecules (SMMs) may improve the hemocompatibility of hemodialyzers. This trial aims to assess the performance and safety of a novel dialyzer with a fluorinated polyurethane SMM, Endexo™. Methods: This prospective, sequential, multicenter, open-label study (NCT03536663) was designed to meet regulatory requirements for clinical testing of new hemodialyzers, including assessment of the in vivo ultrafiltration coefficient (Kuf). Adults prescribed thrice-weekly hemodialysis were eligible for enrollment. After completing 12 hemodialysis sessions with an Optiflux® F160NR dialyzer, patients received 38 sessions with the dialyzer with Endexo. Evaluated parameters included the in vivo Kuf of the dialyzer with Endexo extent of removal of urea, albumin, and β2-microglobulin (β2M), as well as complement activation. Results: Twenty-three patients received 268 hemodialysis treatments during the Optiflux period, and 18 patients received 664 hemodialysis treatments during the Endexo period. Three serious adverse events were reported, and none of them were considered device related. No overt complement activation was observed with either dialyzer. Both dialyzers were associated with comparable mean increases in serum albumin levels from pre- to posthemodialysis (Optiflux: 7.9%; Endexo: 8.0%). These increases can be viewed in the context of a mean increase in hemoglobin of approximately 5% and a mean ultrafiltration volume removed of approximately 2.2 L. The corrected mean β2M removal rate was 47% higher during the Endexo period (67.73%). Mean treatment times (208 vs. 205 min), blood flow rates (447.7 vs. 447.5 mL/min), dialysate flow rates (698.5 vs. 698.0 mL/min), urea reduction ratio (82 vs. 81%), and spKt/V (2.1 vs. 1.9) were comparable for the Endexo and Optiflux periods, respectively. The mean (SD) Kuf was 15.85 (10.33) mL/h/mm Hg during the first use of the dialyzer with Endexo (primary endpoint) and 16.36 (9.92) mL/h/mm Hg across the Endexo period. Conclusions: The safety of the novel dialyzer with Endexo was generally comparable to the Optiflux dialyzer, while exhibiting a higher β2M removal rate.

Heparin immobilized graphene oxide in polyetherimide membranes for hemodialysis with enhanced hemocompatibility and removal of uremic toxins

Intermittent hemodialysis is a life-saving renal replacement therapy that removes excess water and uremic salts from patients who suffer from loss of kidney function. Hemocompatible polyetherimide membranes were fabricated by the incorporation of functionalized graphene oxide (f-GO). The f-GO was prepared by immobilizing heparin via the polydopamine anchor onto the nanosheets. The role of the f- GO in altering membrane morphology, surface roughness, wettability, porosity, and surface chemistry were evaluated in detail. The addition of f-GO suppressed the protein adsorption from platelet-poor plasma (>90%) lowered the adhesion (103 times)/activation of platelets, improved the blood clotting time (aPTT/TCT - ~235 s/58.5 s), decreased the thrombin generation and did not activate either complement pathways. Low aggregation of erythrocytes and <2% hemolysis ratio was another indication of improved membrane hemocompatibility. The cell proliferation of Chang liver cells on the f-GO incorporated membranes is an indication of low cytotoxicity of the prepared membranes. The modified hollow fiber membranes displayed exceptional capabilities compared to its pristine counterpart, evidenced by ~ four times higher ultrafiltration coefficient, outstanding removal of uremic toxins after 4 h (Urea- 77 ± 2.5%, creatinine- 68 ± 2% and Lysozyme 44 ± 2%) and ~95% retention of essential protein (albumin). No leaching of the f-GO could be observed from the membrane, and the prepared membranes were robust as they exhibited a sufficiently high solute removal (urea, creatinine, and phosphate) in the ex-vivo run using spiked goat blood. These preliminary investigations point to the fact that f-GO is a suitable modifier, and these membranes can be further explored for hemodialysis application.

Chemical Degradation of PSF-PUR Blend Hollow Fiber Membranes-Assessment of Changes in Properties and Morphology after Hydrolysis.

In this study, we focused on obtaining polysulfone-polyurethane (PSF-PUR) blend partly degradable hollow fiber membranes (HFMs) with different compositions while maintaining a constant PSF:PUR = 8:2 weight ratio. It was carried out through hydrolysis, and evaluation of the properties and morphology before and after the hydrolysis process while maintaining a constant cut-off. The obtained membranes were examined for changes in ultrafiltration coefficient (UFC), retention, weight loss, morphology assessment using scanning electron microscopy (SEM) and MeMoExplorer™ Software, as well as using the Fourier-transform infrared spectroscopy (FT-IR) method. The results of the study showed an increase in the UFC value after the hydrolysis process, changes in retention, mass loss, and FT-IR spectra. The evaluation in MeMoExplorer™ Software showed the changes in membranes’ morphology. It was confirmed that polyurethane (PUR) was partially degraded, the percentage of ester bonds has an influence on the degradation process, and PUR can be used as a pore precursor instead of superbly known polymers.

Additive-free preparation of hemodialysis membranes from block copolymers of polysulfone and polyethylene glycol

Hemodialysis membranes have been widely used for the treatment of chronic kidney disease. However, as common hemodialysis membranes, polysulfone based membranes are suffering from complicated modification to improve hemocompatibility and safety issues of additive leaching-out. Facing these challenges, here hemodialysis membranes with excellent hemocompatibility and biocompatibility were fabricated by nonsolvent induced phase separation (NIPS) of a block copolymer, polysulfone-block-poly(ethylene glycol) (PSF-b-PEG), without using any additives. During NIPS, mesopores were formed throughout the membrane and the PEG chains were preferentially enriched on surfaces, thus improving the hydrophilicity. In-vitro compatibility and performance of the PSF-b-PEG membranes as well as protein adsorption, hemolysis, platelet adhesion, ultrafiltration coefficient, solute rejection and toxin clearance were studied. Due to the intrinsic existence of hydrophilic and biocompatible PEG on surface, the PSF-b-PEG membranes exhibited superior hemodialysis performances than traditional membranes, demonstrating their promise for hemodialysis.

Flow balance optimization and fluid removal accuracy with the Quanta SC+ hemodialysis system

ABSTRACT Background Fluid management is integral to hemodialysis, both to correct abnormalities in a patient’s plasma composition and to maintain fluid balance. Consequently, accurate net fluid removal during treatment is a critical design element of hemodialysis machines. As dialyzers have evolved, with increased ranges of ultrafiltration coefficients available, it has become more challenging for dialysis machines to minimize errors in flow balance and net fluid removal. Research design and methods This paper describes the design, evaluation and experimental performance of the flow balance and ultrafiltration module of the SC+ system to deliver clinically specified fluid removal with both passive and active control measures, in laboratory conditions designed to simulate a wide range of therapies. Results The use of passive and active control allows the errors to be minimized across a wider dynamic range of conditions. For the SC+ system, the average flow balance error was 1 mL/hr with an SD of 19 mL/hr and with ultrafiltration it was 13 mL/hr and an SD of 20 ml/hr across all conditions. Conclusions This paper demonstrates that the SC+ hemodialysis system, a small, simple and versatile CE marked device, operates within the limits required by international standards across a wide range of experimental conditions.

The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-induced Hypertension.

Purinergic receptors play a central role in the renal pathophysiology of angiotensin II-induced hypertension, since elevated ATP chronically activates P2X7 receptors in this model. The changes induced by the P2X antagonist Brilliant blue G (BBG) in glomerular hemodynamics and in tubulointerstitial inflammation resulting from angiotensin II infusion were studied. Rats received angiotensin II (435 ng kg−1 min−1, 2 weeks) alone or in combination with BBG (50 mg/kg/day intraperitoneally). BBG did not modify hypertension (214.5 ± 1.4 vs. 212.7 ± 0.5 mmHg), but restored to near normal values afferent (7.03 ± 1.00 to 2.97 ± 0.27 dyn.s.cm−5) and efferent (2.62 ± 0.03 to 1.29 ± 0.09 dyn.s.cm−5) arteriolar resistances, glomerular plasma flow (79.23 ± 3.15 to 134.30 ± 1.11 nL/min), ultrafiltration coefficient (0.020 ± 0.002 to 0.036 ± 0.003 nL/min/mmHg) and single nephron glomerular filtration rate (22.28 ± 2.04 to 34.46 ± 1.54 nL/min). Angiotensin II induced overexpression of P2X7 receptors in renal tubular cells and in infiltrating T and B lymphocytes and macrophages. All inflammatory cells were increased by angiotensin II infusion and reduced by 20% to 50% (p < 0.05) by BBG administration. Increased IL-2, IL-6, TNFα, IL-1β, IL-18 and overexpression of NLRP3 inflammasome were induced by angiotensin II and suppressed by BBG. These studies suggest that P2X7 receptor-mediated renal vasoconstriction, tubulointerstitial inflammation and activation of NLRP3 inflammasome are associated with angiotensin II-induced hypertension.

SUN-255 THE EFFECT OF HEMODIALYSIS ON HscTnI LEVELS AMONG ASYMPTOMATIC CKD PATIENTS IN A TERTIARY HOSPITAL IN DAVAO CITY

Mild chest pains or discomforts occur in 1 to 4% of Chronic Kidney Disease (CKD) patients on hemodialysis (HD). Cardiac Troponins play a pivotal role in the diagnosis of Acute Coronary Syndrome (ACS). Chronic HD patients have increased cardiac troponins that may not be due to ACS, but subclinical myocardial damage. Interpretation of cardiac troponin assay among these patients constitutes a big challenge. Equally important is to know the behavior of troponins during HD. To date, it has not been clearly elucidated whether HD can affect the level of cardiac troponins1,2,3. Literatures showed that HD decreases the level of cardiac troponins immediately post procedure2,5, while others have shown an increase6. Such ambiguity makes clinicians more confused in interpreting cardiac troponin among CKD patients. This study aims to determine the effect of HD in high sensitivity cardiac troponin I (HscTnI) levels among CKD patients and identify factors that are potential sources of variability that can affect the interpretation of HscTnI. This is a prospective study conducted in a tertiary hospital. 44 asymptomatic CKD patients on maintenance HD were enrolled. Sampling was purposive. Exclusion criteria included HD vintage of less than 6 months, critical illness, infection, myocardial infarction in the last 30 days, and coronary angioplasty or cardiac surgery in the last 12 months. Pre-HD and immediate post-Hd HscTnI were measured using HscTnI ARCHITECTSTAT assay by Abbott. Demographic data, ultrafiltration coefficient of membranes either hi-flux or low-flux, and the frequency of membrane dialyzer reuse were noted. 23/44 (52%) of the study population had elevated pre-HD HscTnI based on the cut-off range provided by the manufacturer. Comparative analysis using paired T-test to determine significant difference between pre- and post-HD HscTnI showed that pre-HD HscTnI is higher (M=60.96, SD=75.64) than post-HD levels (M=60.65, SD=78.06), with a 0.16 ng/L difference. Paired T-test result showed that the difference is not significant (p value=0.9) at 5% level of significance. We regrouped patients according to their type of membrane dialyzer (Hi-flux and Low-flux). Many from low-flux group had decreased HscTnI post-HD than in the hi-flux group, contrary to what was expected. Hi-Flux membranes are supposed to clear macromolecules better. Further investigation found that most in the hi-flux group reused their dialyzer membranes 3-6x, while most membranes in the low-flux group were new. Analysis using Pearson Product Moment Correlation revealed a significant correlation between the number of usage of dialyzer to the change in the level of HscTnI post HD (Table 3). A comparative analysis using T-test for two proportions also found a significant correlation between single use membrane dialyzer and decrease in the level of HscTnI post-HD. Hemodialysis, in general, did not significantly affect the levels of HscTnI. Frequency of membrane reuse is a factor that affects HD performance and clearance of HscTnI. The more frequency of dialyzer reuse, the lesser the clearance of HscTnI.

Randomised trial on clinical performances and biocompatibility of four high-flux hemodialyzers in two mode treatments: hemodialysis vs post dilution hemodiafiltration

This prospective multicenter randomized comparative cross-over trial aimed at evaluating the influence of hemodialysis vs post-dilution hemodiafiltration with high-flux dialyzers in solute clearance and biocompatibility profile. 32 patients were sequentially dialyzed with Leoceed-21HX, Polypure-22S+, Rexsys-27H and VIE-21A. Primary outcome was β2-microglobulin removal. Secondary outcomes were (i) extraction of other uremic solutes (ii) parameters of inflammation and nutrition and (iii) comparative quantification of perdialytic albumin losses (using total ‘TDC’ vs partial ‘PDC’ collection of dialysate). Significant increases in removal rates of β2-microglobulin (84.7 ± 0.8 vs 71.6 ± 0.8 mg/L), myoglobin (65.9 ± 1.3 vs 38.6 ± 1.3 µg/L), free immunoglobulin light chains Kappa (74.9 ± 0.8 vs 55.6 ± 0.8 mg/L), β-trace protein (54.8 ± 1.3 vs 26.8 ± 1.4 mg/L) and orosomucoid (11.0 ± 1.1 vs 6.0 ± 1.1 g/L) but not myostatin (14.8 ± 1.5 vs 13.0 ± 1.5 ng/mL) were observed in HDF compared to HD when pooling all dialyzers. Rexsys and VIE-A use in both HD and HDF subgroups was associated to a better removal of middle/large-size molecules compared to Leoceed and Polypure, except β2-microglobulin for Rexsys. Inflammatory parameters were unchanged between dialyzers without any interaction with dialysis modality. Mean dialysate albumin loss was comparable between TDC and PDC (1.855 vs 1.826 g/session for TDC and PDC respectively). In addition, a significant difference in albumin loss was observed between dialyzers with the highest value (4.5 g/session) observed using Rexsys. Use of all dialyzers was associated with good removals of the large spectrum of uremic toxins tested and good biocompatibility profiles, with an additional gain in removal performances with HDF. Larger surface area, thinner wall and resultant very high ultrafiltration coefficient of Rexsys should be taken into account in its clear performance advantages.

Heparin reduced dialysis through a facile anti-coagulant coating on flat and hollow fiber membranes

Heparin free prescription is highly desired for haemodialysis. Versatile strategies have been developed to address the anti-coagulation modification of dialysis membranes. We here develop a facile and effective method to construct an anticoagulant coating on polymeric membranes or a dialyzer through hydrophobic-hydrophobic interaction. An amphiphilic heparin-like copolymer was first synthesized via a free radical polymerization based on alkyl chain lauryl methacrylate (LMA), acrylic acid (AA), and sodium 4-vinylbenze-sulfonate (SSNa) segments. The specific structure of terpolymer was characterized via Fourier transform infrared spectra (FTIR), Proton nuclear magnetic resonance (1H NMR) spectra and size exclusion chromatography (SEC). The amphiphilic copolymer was anchored onto Polylactide (PLA) membrane surface from an aqueous-based solution via hydrophobic-hydrophobic interaction. An Attenuated total reflectance Fourier transform infrared spectra (ATR-FTIR), energy dispersive spectrometer (EDS) and X-ray photoelectron spectroscopy (XPS) confirmed the successful immobilization of heparin-mimicking terpolymers. The modified membranes showed excellent antifouling property and hydrophilicity. Moreover, the membranes exhibited outstanding haemocompatibility with suppressed platelet adhesion, low complement activation (C3a and C5a), expanded coagulation time and limited haemolysis ratio. The prolonged activated partial thromboplastin time and thrombin time (APTT>600 s, TT > 140 s) certified the excellent self-anticoagulant performances. To further examine the applicability and effectiveness, a polysulfone dialyzer was modified by this strategy. The ultrafiltration coefficient and clearance performances were examined. Overall, the hydrophobic-hydrophobic interaction strategy simplified the modification procedure of dialysis membrane, implying its great potential in heparin free dialysis application.

Correlation between Ultrafiltration Coefficient and Effective Lymphatic Absorption Rate in Continuous Ambulatory Peritoneal Dialysis Patients: A Possible Paradigm Shift.

Background:The relative contribution of transcapillary water movement and lymphatic reabsorption in peritoneal dialysis (PD) is a critical issue, particularly in patients with ultrafiltration failure (UFF). Based on routine results obtained from the PD Adequest 2.0 software, the present study aimed to re-evaluate the separate effects of transcapillary water movement and lymphatic reabsorption on the net ultrafiltration capacity in continuous ambulatory peritoneal dialysis (CAPD) patients without UFF. Methods:Seventy CAPD patients without UFF and PD duration less than 2 years entered the study. The study was conducted during January-April 2016 at Mashhad University of Medical Sciences, Mashhad, Iran. Each patient had 1 to 3 peritoneal equilibration test (PET) results which were used to analyze the determinants of fluid transport, lymphatic reabsorption, and ultrafiltration. Pearson and Spearman correlation tests were used to determine the correlation between continuous and ordinal factors, respectively. The data were analyzed using the SPSS software version 19.0. Results:In terms of the effective lymphatic absorption rate (ELAR) and ultrafiltration coefficient (LpA) values, there was no difference in the high or high-average transporters compared to the low or low-average transporters. However, a positive and highly significant correlation between ELAR and LpA was found. Conclusion: A significant correlation between ELAR and LpA was found in CAPD patients without UFF and duration less than 2 years from the beginning of PD. The abstract was presented in the 53rd ERA-EDTA Congress, Austria, as a poster and published in Nephrology Dialysis Transplantation as a supplement (2016; Vol. 31).

Clinical evaluation of performance, biocompatibility, and safety of vitamin E-bonded polysulfone membrane hemodialyzer compared to non-vitamin E-bonded hemodialyzer

The vitamin E-bonded polysulfone membrane hemodialyzer (ViE™-21) was evaluated in a clinical study for regulatory submission. Seventeen patients on hemodialysis were treated with conventional high-flux hemodialyzers for 2 weeks (Pre-ViE phase) and switched to the ViE-21 for 36 sessions (ViE phase) followed by an additional 2 weeks on conventional hemodialyzers (Post-ViE phase). Reduction ratios of urea, creatinine, beta-2-microglobulin, albumin, and ultrafiltration coefficients (KUF) were measured once during the Pre-ViE phase and twice during the ViE phase. Moreover, biocompatibility markers [leucocyte count, platelet count, and activated complement factor (C3a) levels] were evaluated pre-dialysis, 15 min after initiation, and post-dialysis. During the study, type and number of adverse events (AEs), and device malfunctions were recorded. ViE-21 reduction ratios and KUF were not noticeably different than those of conventional hemodialyzers. Fluctuations of leucocyte counts and C3a concentrations were similar using ViE-21 and conventional hemodialyzers; however, the platelet count fluctuation was lower in ViE-21 sessions. The frequency of episodes of hypotension occurring during the ViE phase was lower than that occurring during the Pre- and Post-ViE phases. In conclusion, this study provided performance and safety data of the ViE-21 for regulatory application. The data suggest that vitamin E-bonded hemodialyzers are beneficial in lowering platelet activation and frequency of intradialytic hypotension. Larger randomized controlled trials are needed to confirm these findings.

Preparation and evaluation of a self-anticlotting dialyzer via an interface crosslinking approach

It is challenging to improve the hemocompatibility of commercial dialyzers packaging more than 10,000 fibers. Herein, we report the preparation and evaluation of a self-anticlotting Polysulfone dialyzer via an interface crosslinking approach. By modulating the conformation of sulfate, carboxyl groups and pyrrolidone (VP) in heparin-like polymers, the hemocompatibility of the dialyzer was significantly improved. It was found that the sequential structure of functional groups influenced the anticoagulant performances substantially. The hollow fiber modified by the blended polymer (Poly (N-vinyl-2-pyrrolidone-co-triethoxyvinylsilane) and poly (Sodium 4-vinylbenzenssulfonate-co-triethoxyvinylsilane-co-Acrylic acid) (P(VP-VTES)-b-P(SSNa-VTES-AA))) exhibited better hemocompatibility than the contrast membrane modified by poly (Acrylic acid-co-triethoxyvinylsilane-co -N-vinyl-2-pyrrolidone-co- -co-Sodium 4-vinylbenzenssulfonate) (P(AA-VTES-VP-SSNa)). The chemical composition was determined by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectra (FTIR). The morphology of the hollow fiber membranes was observed by a scanning electron microscopy (SEM). The thrombin time (TT), plasma fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT) and protein adsorption were measured to examine the hemocompatibility. The modified hollow fiber showed self-anticlotting properties with excellent protein resistance, remarkably prolonged coagulation time (APTT > 600 s), suppressed complement activation and nontoxicity to osteoblasts. The modified dialyzer showed practicable ultrafiltration coefficient and clearance performance, indicating its great potential application in dialysis treatment.