#3944 Comparison of Clinical Performance and Hemocompatibility of Dialyzers Applied During Post-Dilution Online Hemodiafiltration (Hdf) – Empora Iii Study

Abstract

Background and Aims Performance and hemocompatibility are the two main functions of a hemodialyzer. Synthetic dialysis membranes made from polysulfone (PSU) or polyethersulfone (PES) are mainly used for dialysis treatments and are blended with the hydrophilic agent polyvinylpyrrolidone (PVP), to improve hemocompatibility during dialysis treatments. A novel PSU-based dialyzer (FX CorAL) with an increased and stabilized PVP content has been developed and has shown strong performance and a favourable hemocompatibility profile within previous short term clinical studies. In the present clinical study, we now investigated the performance and hemocompatibility of the FX CorAL vs. two comparators over a longer follow-up time and applied an extended panel of hemocompatibility biomarkers. This allowed us to analyse treatment-specific performance as well as an extensive intra- and interdialytic hemocompatibility profile. Method eMPORA III was a prospective, open, controlled, multicentre crossover trial with randomized treatment sequences conducted in DE, CZ and HU. It randomized stable patients receiving regular post-dilution online HDF to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun), each for 4 weeks. The primary outcome was β2-m removal rate (RR) during 4 hrs HDF. Non-inferiority (margin: 5%) and superiority of FX CorAL 600 versus comparators were tested at α = 2.5% (one-sided), with adjustment for multiple tests. Secondary endpoints were RR and/or clearance of β2-m and other molecules, as well as intra- and interdialytic changes of markers of complement activation (C3a, sC5b-9), cell activation / inflammation (white blood cells (WBC), PMN elastase, IL-6, IL-8, LTB-4, sICAM-1, hsCRP), platelet activation (platelet count, β-TG, TxB-2), and oxidative stress (MDA, GSH-Px). Intradialytic hemocompatibility markers were analysed descriptively as differences vs. the values determined at the start of the HDF session (LS means). Results Eighty-two patients were included and analysed in the safety population, with n = 76 presenting data for the primary outcome (ITT population). FX CorAL 600 showed the highest β2-m RR (LS mean: 76.31%), followed by FX CorDiax 600 (75.71%) and xevonta Hi 15 (74.49%). Non-inferiority to its comparators was statistically significant (p<0.0001 each). Superiority was shown vs. xevonta Hi 15 (p<0.0001), but not vs. FX CorDiax 600 (p = 0.0606). The secondary endpoints β2-m clearance as well as myoglobin clearance and RR affirmed these results; small molecule clearances and/or RR were similar between dialyzers. Analyses of hemocompatibility markers within one HDF session, found the following significant differences: Complement activation • C3a 15 min: FX CorAL: 31%; FX CorDiax: 59% (p = 0.003 vs. FX CorAL); xevonta: 41% (p = 0.029 vs. FX CorAL) • sC5b-9 60 min: FX CorAL: 24%; FX CorDiax: 25% (p = 0.337); xevonta: 41% (p<0.0001) Cell activation/ Inflammation • WBC 15 min: FX CorAL: -7.7%; FX CorDiax: -11.1% (p = 0.015); xevonta: -10.1% (p = 0.246) • Monocytes 15 min: FX CorAL: -30.9%; FX CorDiax: -30.3% (p = 0.533); xevonta: -38.2% (p = 0.012) • Neutrophils 15 min: FX CorAL: -3.0%; FX CorDiax: -7.5% (p = 0.019); xevonta: -6.1% (p = 0.258) • PMN elastase 60 min: FX CorAL: 18%; FX CorDiax: 42% (p = 0.003); xevonta: 52% (p = 0.0003) • LTB-4 15 min: FX CorAL: 170%; FX CorDiax: 217% (p = 0.047); xevonta: 186% (p = 0.539) Platelet activation • β-TG 60 min: FX CorAL: -15%; FX CorDiax: 4% (p<0.0001); xevonta: 18% (p<0.0001) Hemocompatibility markers showed no interdialytic changes, i.e., no significant changes within treatment periods. Nine serious adverse events occurred in this study, none of which was dialyser related. Conclusion FX CorAL 600 efficiently removed middle and small molecules and was non-inferior to both comparators and significantly superior to xevonta Hi 15 in β2-m RR. The typical drop in WBC, monocyte, and neutrophil count during dialysis as well as the rise of complement (C3a, sC5b-9) and cell / platelet activation markers (PMN elastase, LTB-4 and β-TG) were lower or comparable during treatment with FX CorAL vs. both comparators, indicating superior hemocompatibility properties.

Hydrophilic Modification of Dialysis Membranes Sustains Middle Molecule Removal and Filtration Characteristics

“…In summary, these β2-microglobulin results support previous findings that the hydrophilic modification of the FX CorAL reduces protein adsorption to the membrane and stabilizes the performance over time [12,19,38]. Moreover, these experimental data are in line with previous clinical trials, which consistently showed the highest β2microglobulin removal as compared to other polysulfone-, polyethersulfone-, or cellulosebased dialyzers [37,[39][40][41].…”

“…These experimental studies are backed by four clinical studies (comPERFORM, eM-PORA, eMPORA II, and eMPORA III) [37,[39][40][41]. All studies investigated β2-microglobulin removal during HDF treatment as the primary outcome and compared the FX CorAL to other polysulfone-, polyethersulfone-, or cellulose-based dialyzers.…”

“…Experimental studies showed a strong correlation between the low protein adsorption by the FX CorAL and the good hemocompatibility profile as well as low sieving coefficient changes over time [19,38]. In clinical studies, the FX CorAL consistently showed the highest β2-microglobulin removal rates and low activation of important hemocompatibility markers, such as complement activation, when compared to other polysulfone-, polyethersulfone-, and cellulose-based dialyzers [37,[39][40][41].…”

“…The novel FX CorAL dialyzer contains such a hydrophilic membrane with increased PVP content on the blood-side surface and was shown in clinical and experimental studies to induce lower protein adsorption than other commonly used dialyzers in clinical practice [12,[36][37][38]. Moreover, the FX CorAL dialyzer was previously compared to other polysulfone-, polyethersulfone-, and cellulose-based dialyzers with regard to performance and hemocompatibility [11,12,19,[36][37][38][39][40][41]. Experimental studies showed a strong correlation between the low protein adsorption by the FX CorAL and the good hemocompatibility profile as well as low sieving coefficient changes over time [19,38].…”