Mo387clinical Performance, Hemocompatibility and Safety of a New Dialyzer With a Modified Polysulfone Membrane

Abstract

Background and Aims Hemodialyzers containing membranes made from a blend of polysulfone and polyvinylpyrrolidone (PVP) are widely used. PVP makes the membrane material more hydrophilic to reduce interactions with plasma proteins and platelets. A modified spinning technique has been established to stabilize the PVP on the blood-side surface in the polysulfone dialysis membrane in the new dialyzer FX CorAL 600. The objective of the present study was to prove for this new dialyzer non-inferiority of performance in comparison to established dialyzers. Further, hemocompatibility and safety of the dialyzers were explored. Method In a multicenter, prospective, randomized, crossover study adult patients on online hemodiafiltration (HDF) were enrolled. They were treated for one week each with on-line HDF in post-dilution mode, and in randomized order with the dialyzers FX CorAL 600, FX 600, and FX CorDiax 600 (all Fresenius Medical Care, Bad Homburg, Germany). Blood samples were taken on the midweek session before start, at the end to analyze removal rate and at 60 min to determine clearance of ß2-microglobulin, myoglobin, urea, creatinine and phosphate. Further a pattern of hemocompatibility parameters and safety was evaluated. Assuming no carry over effect, linear mixed models were used for statistical analysis. Results The mean age of the 49 enrolled patients was 66.3±13.6 years, 76% were male. Treatments were performed in post-dilution mode with a mean blood flow > 300 mL/min and a substitution volume >19 L. The removal rate of ß2-microglobulin was 74.4, 70.4, and 73.1% for the FX CorAL 600, FX 600, and FX CorDiax 600 dialyzer, respectively. FX CorAL 600 proved to be statistically significantly non-inferior to FX 600 (p=0.0006) and to FX CorDiax 600 (p=0.036). The removal rate of FX CorAL 600 was by 4.0% (confidence interval 0.4 – 7.5%) significantly higher than with FX 600. The difference to FX CorDiax 600 was not significant. The clearance of ß2-microglobulin and myoglobin and the removal rate of myoglobin were significantly higher with the new dialyzer FX CorAL 600 than with the FX 600, and comparable to the FX CorDiax 600. Performance for small molecules was similar for all dialyzers. The complement factors C3a and C5a increased early in the treatment with a peak at 15 min, without differences between the three dialyzers for C3a, and for C5a with significantly lower increase at 15 min with FX CorAL 600 than for FX 600 (p=0.007); the difference of increase between FX CorAL 600 and FX CorDiax 600 was not significant (p=0.515). The course of sC5b9 was similar for all three dialyzers, with significantly lower increase at 15 min for both FX CorAL 600 (p=0.009) and FX CorDiax 600 (p=0.026) as compared to FX 600 and similar increase at 60 min for both FX CorAL 600 (p=0.573) and FX CorDiax 600 (p=0.386) as compared to FX 600. The area-under-the-curve for the course of sC5b-9 with FX CorAL 600 was significantly lower than with FX 600 (p=0.044) and comparable to FX CorDiax 600 (p=0.092). The leukocyte count showed a decrease in the first 15 min of the treatment, which recovered afterwards, similarly for all treatment phases with the different dialyzers. Further, the dialyzers did not differ with respect to adverse events. Conclusion All three dialyzers showed good performance, with higher removal rates for middle molecules with the new dialyzer FX CorAL 600 compared to the FX 600. Hemocompatibility profiles were mostly similar, with lower activation of C5a and of sC5b9 with FX CorAL 600 compared to FX 600. The new dialyzer provides comparable performance levels capable of delivering adequate treatment and good tolerability for the patient.

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].…”

Randomized investigation of increased dialyzer membrane hydrophilicity on hemocompatibility and performance

“…Three earlier clinical trials evaluated FX CorAL 600 during short treatment periods [ 11 , 19 , 20 ]. FX CorAL showed the highest β2-m removal rates (RR) as compared to synthetic and cellulose-based comparator dialyzers.…”