Randomized investigation of increased dialyzer membrane hydrophilicity on hemocompatibility and performance.

BACKGROUND: Hemodialyzers should efficiently eliminate small and middle molecular uremic toxins and possess exceptional hemocompatibility to improve well-being of patients with end-stage kidney disease. However, performance and hemocompatibility get compromised during treatment due to adsorption of plasma proteins to the dialyzer membrane. Increased membrane hydrophilicity reduces protein adsorption to the membrane and was implemented in the novel FX CorAL dialyzer. The present randomized controlled trial compares performance and hemocompatibility profiles of the FX CorAL dialyzer to other commonly used dialyzers applied in hemodiafiltration treatments. METHODS: This prospective, open, controlled, multicentric, interventional, crossover study randomized stable patients on post-dilution online hemodiafiltration (HDF) to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun) each for 4 weeks. Primary outcome was ß2-microglobulin removal rate (ß2-m RR). Non-inferiority and superiority of FX CorAL versus comparators were tested. Secondary endpoints were RR and/or clearance of small and middle molecules, and intra- and interdialytic profiles of hemocompatibility markers, with regards to complement activation, cell activation/inflammation, platelet activation and oxidative stress. Further endpoints were patient reported outcomes (PROs) and clinical safety. RESULTS: 82 patients were included and 76 analyzed as intention-to-treat (ITT) population. FX CorAL showed the highest ß2-m RR (76.28%), followed by FX CorDiax (75.69%) and xevonta (74.48%). Non-inferiority to both comparators and superiority to xevonta were statistically significant. Secondary endpoints related to middle molecules corroborated these results; performance for small molecules was comparable between dialyzers. Regarding intradialytic hemocompatibility, FX CorAL showed lower complement, white blood cell, and platelet activation. There were no differences in interdialytic hemocompatibility, PROs, or clinical safety. CONCLUSIONS: The novel FX CorAL with increased membrane hydrophilicity showed strong performance and a favorable hemocompatibility profile as compared to other commonly used dialyzers in clinical practice. Further long-term investigations should examine whether the benefits of FX CorAL will translate into improved cardiovascular and mortality endpoints. TRIAL REGISTRATION: eMPORA III registration on 19/01/2021 at ClinicalTrials.gov (NCT04714281).

Randomized comparison of three high-flux dialyzers during high-volume online hemodiafiltration-the comPERFORM study.

Background: Dialyzers should be designed to efficiently eliminate uraemic toxins during dialysis treatment, given that the accumulation of small and middle molecular weight uraemic 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 performance during online hemodiafiltration (HDF) in a clinical setting. Methods: comPERFORM was a prospective, open, controlled, multicentric, interventional, crossover study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online HDF to FX CorAL 600 (Fresenius Medical Care Deutschland), xevonta Hi 15 (B. Braun) and ELISIO 150H (Nipro) each for 1 week. The primary outcome was ß2-m 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 versus comparators were tested. Results: Fifty-two patients were included and analysed. 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 comparators was statistically significant (P = 0.0216 and P < 0.0001, respectively). Secondary endpoints related to middle molecules affirmed these results. FX CorAL 600 demonstrated the lowest albumin removal up to 60 minutes and its sieving properties changed less over time than with comparators. 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 reduced formation of a secondary membrane.

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

Background: 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. Methods: 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 ß2-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. Results: Of 70 patients, 58 composed the intention-to-treat population. The FX CorAL 600's removal rate of ß2-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. Conclusions: 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.