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

Abstract

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 < 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.

Time‐resolving characterization of molecular weight retention changes among three synthetic high‐flux dialyzers

“…Moreover, comPERFORM investigated the amount of albumin, which was lost into the dialysate during the treatment sessions. Here, in line with our present experimental data, xevonta showed the highest albumin loss after 4 h (1.53 ± 0.80 g), followed by FX CorAL (1.36 ± 0.71 g) and ELISIO (1.10 ± 0.60 g) 22 . Of note, the total amount of albumin loss was higher in the clinic than in the present experimental setting.…”

“…We investigated the three dialyzers FX CorAL (Fresenius Medical Care), ELISIO (Nipro), and xevonta (B. Braun) used in the clinical study comPERFORM (Comparative Clinical Performance of Dialyzers Applied During High Volume Online Hemodiafiltration, NCT04102280). 22 Table 1 summarizes information for dialyzers according to Nalesso et al, 23 for the following categories: Membrane/Area, Coefficients, Clearances, Sieving Coefficients, and Modality. For the categories SC-MW (molecular weight retention onset and molecular weight cut-off) and RR (middle and high molecular weight reduction rate) the manufacturers provide no information in the respective instructions for use or brochures.…”

Impact of Hydrophilic Modification of Synthetic Dialysis Membranes on Hemocompatibility and Performance

“…Membranes with a thicker protein layer have a stronger reduction in performance, which is associated with stronger reduction in the effective pore size of the dialyzer membranes [ 58 , 60 ]. Data from a recent randomized controlled trial with 52 hemodialysis patients treated with three different synthetic dialyzers in a cross-over design, support these findings, showing superiority in β2-microglobulin removal rate for that dialyzer that had the lowest secondary membrane formation (75.5% vs. 74.0% and 72.7%; p = 0.0216 and p < 0.0001, respectively) [ 37 ]. Therefore, these blood-membrane interactions influence the efficacy of the dialysis treatment and have to be taken into considerations beyond the clearance values presented in the instructions for use of the dialyzers.…”

“…Repeated protein loss may lead to the development of malnutrition, which is associated with increased mortality among ESKD patients [ 34 , 35 , 36 ]. Therefore, albumin has become an established key parameter of nutritional status of hemodialysis patients and has also been used in studies investigating protein leakage into the dialysate [ 37 ]. Thus, the performance of a dialyzer is not sufficiently described by its clearance or removal of middle size toxins and should consider its sieving properties overall, including its permeability cut-off for larger size proteins.…”

Clinical Management of Hemodialyzed Patients: From Pharmacological Interventions to Advanced Technologies

“…Moreover, all these bone-derived products, whose levels achieve even 1000-fold above the physiological limit in HD patients, belong to the group of uremic toxins. Current strategies decrease their serum concentration through dietary and pharmacological interventions, mainly via modulation of intestinal absorption capacity through binding effects and/or reduction of ingested amounts of the toxins or their precursors, and by extra-corporeal removal [ 18 , 19 ].…”