Dialytic clearance of p-cresyl sulfate (pCS) and other protein-bound toxins is limited by diffusive and convective therapies, and only a few studies have examined how to improve their removal by adsorptive membranes. This study tested the hypothesis that high-flux polymethylmethacrylate (PMMA) dialysis membranes with adsorptive capacity increase pCS removal compared to polysulfone membranes, in a postdilution on-line hemodiafiltration (OL-HDF) session. Thirty-five stable hemodialysis patients randomly completed a single study of 4 h OL-HDF with PMMA (BG2.1U, Toray®, Tokyo, Japan) and polysulfone (TS2.1, Toray®) membranes. The primary endpoint was serum pCS reduction ratios (RRs) obtained with each dialyzer. Secondary outcomes included RRs of other solutes such as β2-microglobulin, the convective volume obtained after each dialysis session, and the dialysis dose estimated by ionic dialysance (Kt) and urea kinetics (Kt/V). The RRs for pCS were higher with the PMMA membrane than those obtained with polysulfone membrane (88.9% vs. 58.9%; p < 0.001), whereas the β2-microglobulin RRs (67.5% vs. 81.0%; p < 0.001), Kt (60.2 ± 8.7 vs. 65.5 ± 9.4 L; p = 0.01), Kt/V (1.9 ± 0.4 vs. 2.0 ± 0.5; p = 0.03), and the convection volume (18.8 ± 2.8 vs. 30.3 ± 7.8 L/session; p < 0.001) were significantly higher with polysulfone membrane. In conclusion, pCS removal by OL-HDF was superior with high-flux PMMA membranes, appearing to be a good dialysis strategy for improving dialytic clearance of pCS, enabling an acceptable clearance of β2-microglobulin and small solutes.

Background and Aims Hemodiafiltration with regeneration of the ultrafiltrate (HFR) is a highly biocompatible dialysis technique that combines convection, diffusion, and adsorption. SUPRA-H is a new HFR system which uses a high-flux dialyzer in the diffusive stage to improve large uremic toxin removal. The aim of our study was to compare the toxin removal of the SUPRA-H system with high-volume online-hemodiafiltration (OL-HDF). Method In an open, randomized, cross-over, single-center, controlled study, 16 adult chronic hemodialysis patients were treated with SUPRA-H or OL-HDF. Hemodialysis sessions were delivered with Flexya dialysis monitor (Medtronic) in the middle-week session, lasting four hours. OL-HDF session was performed in post-dilution mode with the same high-flux dialyzer (Phylter HF17G, Medtronic) as that used in the diffusive stage of the SUPRA-H system. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of urea, creatinine, phosphate, β2-microglobulin (β2mglob), kappa (κFLC) and lambda (λFLC) free light chains, interleukin-6 (IL-6) p-Cresyl sulfate, indoxyl sulfate and albumin, was intraindividually compared for the two dialysis types with linear mixed models. Results Whereas urea RR was significantly lower, SUPRA-H had significantly higher RR for κFLC (Median: 58.63%, IQR: 49.91-70.24) than those obtained with OL-HDF (Median: 51.97%, IQR: 37.12-62.71); p = 0.03). The RRs for the other large and protein-bound uremic toxins tended to be higher with the SUPRA-H system (Figure 1). There were no significant differences in the RRs for creatinine, phosphate, IL-6, and albumin. Conclusion The new HFR system SUPRA-H, appears to be a potential technologic step ahead in terms of improved large molecule removal for dialysis patients, and might contribute to a more adequate dialysis therapy.

Background and Aims Dialytic clearance of protein-bound toxins and large middle molecules is poor by diffusive treatment and limited by high-flux hemodialysis (HD) and on-line hemodiafiltration (OL-HDF), and only a few studies have examined how to improve their removal by other extracorporeal strategies. Since 2017, there is a new generation of polymethyl methacrylate (PMMA) membranes that suppress platelet adhesion on the membrane surface improving hemocompatibility and permeability, while also maintaining adsorption properties related to conventional PMMA membranes. Expanded HD (HDx) with medium cut-off (MCO) membranes has also recently been incorporated into clinical practice and may improve the removal of uremic toxins in HD treatments. The aim of this pilot study was to compare the efficacy of a new high-flux PMMA dialyzer (Filtryzer® NF-2.1H) in a post-dilution OL-HDF session with a new MCO membrane (Theranova® 400) in a HDx session. Method In an open, cross-over, single-center, controlled, prospective clinical study, 40 adult stable HD patients were assigned to be treated by post-dilution OL-HDF with the NF-2.1H dialyzer or by HDx with the Theranova 400 dialyzer. All other dialysis parameters, including blood and dialysate flow rates, length of dialysis session, and ultrafiltration rate remained unchanged during both sessions. P-cresyl sulfate (PCS), indoxyl sulfate (IS), and kappa (κ) and lambda( λ) free light chains (FLC) reduction rates were intraindividually compared for the two dialyzer types (primary outcomes). Secondary outcomes included the kt and the reduction ratio of blood urea nitrogen, phosphate and β2 -microglobulin (β 2-m). Results The reduction ratio of protein-bound toxins ranges from 60% to 67%, with no differences between membranes (Figure). PMMA membrane achieved greater FLC reduction ratios than MCO membrane, reaching significance for λFLC (56.6% vs. 77.4%; p &lt; 0.001). Conversely, β2M reduction ratio was slightly but significantly higher with MCO membrane (68.5 vs. 72.1%; p = 0.002). Small molecules removal including urea and phosphate were similar in both groups, achieving an optimal Kt with no differences between groups (61.3±9.2 Vs. 59.7±9.3; p=0.16). Albumin reduction ratio tended to be higher with PMMA membrane without reaching significance (10.1±5.9% Vs. 7.8±12.3%; p=0.17). The mean convective volume achieved with PMMA was 23.5±4.4 L. Conclusion This study suggested that new high-flux PMMA dialyzer in post-dilution OL-HDF mode might achieve better FLC reduction ratios than MCO dyalizer in HDx mode, whereas both techniques may equally remove protein-bound toxins. OL-HDF with new PMMA membranes could be a good dialysis strategy for adding convective transport to the well-known mechanisms of diffusion and absorption previously described with conventional PMMA membranes, enabling an adequate substitution volume.