Activation of the complement system may occur during blood‐membrane interactions in hemodialysis and contribute to chronic inflammation of patients with end‐stage renal disease. Hydrophilic modification with polyvinylpyrrolidone (PVP) has been suggested to increase the biocompatibility profile of dialysis membranes. In the present study we compared the complement activation of synthetic and cellulose‐based membranes, including the polysulfone membrane with α‐tocopherol‐stabilized PVP‐enriched inner surface of the novel FX CorAL dialyzer, and linked the results to their physical characteristics. Eight synthetic and cellulose‐based dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO, SUREFLUX [Nipro]; xevonta [B. Braun]; FDX [Nikkisio Medical]) were investigated in the present study. Complement activation (C3a, C5a, and sC5b‐9) was evaluated in a 3 hours ex vivo recirculation model with human blood. Albumin sieving coefficients were determined over a 4 hours ex vivo recirculation model with human plasma as a surrogate of secondary membrane formation. Zeta potential was measured as an indicator for the surface charge of the membranes. The FX CorAL dialyzer induced the lowest activation of the three complement factors (C3a: −39.4%; C5a: −57.5%; and sC5b‐9: −58.9% compared to the reference). Highest complement activation was found for the cellulose‐based SUREFLUX (C3a: +154.0%) and the FDX (C5a: +335.0% and sC5b‐9: +287.9%) dialyzers. Moreover, the FX CorAL dialyzer had the nearest‐to‐neutral zeta potential (−2.38 mV) and the lowest albumin sieving coefficient decrease over time. Albumin sieving coefficient decrease was associated with complement activation by the investigated dialyzers. Our present results indicate that the surface modification implemented in the FX CorAL dialyzer reduces the secondary membrane formation and improves the biocompatibility profile. Further clinical studies are needed to investigate whether these observations will result in a lower inflammatory burden of hemodialysis patients.

Introduction: Hydrophilic modification with polyvinylpyrrolidone (PVP) increases the biocompatibility profile of synthetic dialysis membranes. However, PVP may be eluted into the patient's blood, which has been discussed as a possible cause for adverse reactions rarely occurring with synthetic membranes. We investigated the content of PVP and its elution from the blood-side surface from commercially available dialyzers, including the novel FX CorAL, with PVP-enriched and α-tocopherol-stabilized membrane, and link the results to the level of platelet loss during dialysis as a maker of biocompatibility. Methods: Six synthetic, PVP containing, dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO [Nipro]; xevonta [B. Braun]) were investigated in the present study. The content of PVP on blood-side surface was determined with X-ray photoelectron spectroscopy (XPS). The amount of elutable PVP was measured photometrically after 5 h recirculation. The level of platelet loss was evaluated in an ex vivo recirculation model with human blood. Findings: Highest PVP content on the blood-side surface was found for the polysulfone-based FX CorAL (26.3%), while the polyethersulfone-based THERANOVA (15.6%) had the lowest PVP content. Elution of PVP was highest for the autoclave steam-sterilized THERANOVA (9.1 mg/1.6 m 2 dialyzer) and Polyflux (9.0 mg/1.6 m 2 dialyzer), while the lowest PVP elution was found for the INLINE steam sterilized FX CorAL and FX CorDiax (<0.5 mg/1.6 m 2 dialyzer, for both). Highest platelet loss was found for xevonta (+164.4% compared to the reference) and the lowest for the FX CorAL (À225.2%) among the polysulfone-based dialyzers; among the polyethersulfone-based dialyzers, THERANOVA (+95.5%) had the highest and ELISIO (À52.1%) the lowest platelet loss. Discussion: Polyvinylpyrrolidone content and elution differ between commercially available dialyzers and were found to be linked to the membrane material and sterilization method. The amount of non-eluted PVP on the blood-side surface may be an important determinant for the biocompatibility of dialyzers.

Background: Toxin removal capacity (i.e., performance) of a dialyzer is not constant but diminishes during treatment, as the adsorption of proteins to the membrane provides an additional barrier to uremic solutes. We investigated timeresolving molecular weight retention changes among synthetic high-flux dialyzers and compared the results with recent data from a randomized controlled trial. Methods:In plasma recirculation experiments over 240 min, sieving coefficients (SC) for β2microglobulin, myoglobin, and albumin were determined for the FX CorAL (Fresenius Medical Care), ELISIO (Nipro), and xevonta (B. Braun).Molecular weight retention (MWR) curves were generated and the shifts over 120 min were characterized. Effective pore radius was determined, and the predicted albumin loss was compared with clinical data.Results: SC decreased over time for all dialyzers (mean relative decrease across all dialyzers: β2-microglobulin: 8.0% (120 min); myoglobin: 56.6% (240 min); albumin: 94.1% (240 min)). FX CorAL (7.3%, 52.6% and 91.1%) and ELISIO (7.7%, 51.0%, and 93.8%) showed a lower decrease than xevonta (9.0%, 66.2%, and 97.4%).For all dialyzers, MWR curves shifted toward lower molecular weight, with the lowest shift for FX CorAL (by 0.23 nm at SC50%, 120 min) and highest for xevonta (0.50 nm). FX CorAL had the highest slope over time and the smallest decrease in the effective pore radius (2 min: 2.31 nm, 120 min: 2.08 nm). Predicted albumin loss over 4 h was highest for xevonta (609.3 mg) and comparable between ELISIO (283.6 mg) and FX CorAL (313.3 mg).Conclusions: Substantial differences in the temporal performance profile of dialyzers exist. The present approach allows the characterization of dialyzer permeability changes over time using standard, clinically relevant protein markers.

Background Dialyzers shall be designed to efficiently eliminate uremic toxins during a dialysis treatment, given that the accumulation of small and middle molecular weight uremic solutes is associated with increased mortality risk of patients with end-stage renal disease. In the present study we investigated the novel FX CorAL dialyzer with a modified membrane surface for the performance during online-hemodiafiltration in a clinical setting. Methods comPERFORM was a prospective, open, controlled, multi-centric, interventional, cross-over study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online hemodiafiltration (HDF) to FX CorAL 600 (Fresenius Medical Care Deutschland GmbH), xevonta Hi 15 (B. Braun), and ELISIO 150H (Nipro), each for one week. The primary outcome was β2-microglobulin removal rate (ß2-m RR) during online-HDF. Secondary endpoints were RR and/or clearance of ß2-m and other molecules. Albumin removal over time was an exploratory endpoint. Non-inferiority and superiority of FX CorAL 600 vs. competitors were tested. Results 52 patients were included and analyzed. FX CorAL 600 showed the highest ß2-m RR (75.47%), followed by xevonta Hi 15 (74.01%) and ELISIO 150H (72.70%). Superiority to its competitors was statistically significant (P = 0.0216 and P &lt; 0.0001, respectively). Secondary endpoints related to middle molecules affirmed these results. FX CorAL 600 demonstrated the lowest albumin removal up to 60 min, and its sieving properties changed less over time than with competitors. Conclusions FX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in ß2-m RR. Albumin sieving kinetics point to a reduced formation of a secondary membrane.

Background: High-flux dialyzers shall effectively remove uremic toxins and be hemocompatible to minimize intradialytic humoral and cellular stimulation and long-term impact on patient outcomes. A new dialyzer with a modified membrane surface has been tested for performance and hemocompatibility. Methods: This multicenter, prospective, randomized, cross-over study applied for one week each the new polysulfone-based FX CorAL 600 (Fresenius Medical Care, Bad Homburg, Germany), the polyarylethersulfone-based Polyflux 170H (Baxter Healthcare Corporation, Deerfield, IL, USA) and the cellulose-triacetate-based SureFluxTM 17UX (Nipro Medical Europe, Mechelen, Belgium) to assess non-inferiority of removal rate of β2-microglobulin of the FX CorAL 600. Performance was assessed by removal rate and clearance of small and middle molecules. Hemocompatibility was assessed through markers of complement, cell activation, contact activation and coagulation. Results: Of 70 patients, 58 comprised the intention-to-treat population. The removal rate of β2-microglobulin of the FX CorAL 600 was non-inferior to both comparators (P<0.0001 vs SureFluxTM 17UX; P=0.0006 vs Polyflux 170H), and superior to SureFluxTM 17UX. The activation of C3a and C5a with FX CorAL 600 was significantly lower 15 min after treatment start than with SureFluxTM 17UX. The activation of sC5b-9 with FX CorAL 600 was significantly lower over the whole treatment than with SureFluxTM 17UX, and lower after 60 min than with Polyflux 170H. The treatments with FX CorAL 600 were well tolerated. Conclusions: FX CorAL 600 efficiently removed small and middle molecules, showed a favorable hemocompatibility profile and was associated with a low frequency of adverse events in the present 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 long-term treatments of hemodialysis patients to minimize the potential impact on inflammatory processes.