Post-dilution Hemodiafiltration Research Articles

#1094 Hemodiafiltration improves solute clearance without increasing water consumption: an educational bench model for the dialysis ward

Abstract Background and Aims Recently, the positive results of the CONVICE trial have raised the question whether the improved outcome of postdilution high volume HDF (oHDF-p) compared to high flux HD (hfHD) requires increased water consumption. From mathematical modelling it can be shown that oHDF-p always leads to higher low molecular clearance than hfHD at equal total dialysate consumption Qd_tot = Qd_dial + Qs (Qd_dial: dialysate flow through the dialyzer, Qs: substitution flow). This has also been shown in a clinical trial (Mesic et al, HDI 15, p. 522-529). However, mathematical modelling might not be intuitive for everyone, and clinical trials are always influenced by multiple confounders. To add a more intuitive way of reasoning, a simple educational bench model was designed based only on equipment easily available in a standard dialysis clinic which allows to compare dialysis efficiencies based on the urea concentrations as surrogate parameter. Since the fundamental task of dialysis is to cleanse blood from uremic solutes, the treatment modality which at equal resource utilization reduces solute concentration most is the more efficient one! Method Dialysis treatments were simulated in single pass setup using a Fresenius 5008S machine (Fig. 1). Blood inlet was simulated as a fixed urea concentration of 170 mg/dL in dialysate from a 110 L reservoir “cbi”. Treatment parameters were set such that they correspond to effective values in in-vivo treatments: As the mass transfer coefficient is always much higher in vitro with water than in vivo with blood, a small high-flux dialyzer (Fresenius FX40) was used. Blood flow Qb was set to 300 mL/min, corresponding to the in vivo blood water flow for Qb_set ∼ 350 mL/min. Alternating experiments in oHDF-p and hfHD were carried out in triplicate with Qd_tot=400 mL/min and 300 mL/min. This resulted in the settings HDF400, HD400, HDF300 and HD300 (cf. Fig. 1). Qs was set to 100 ml/min in oHDF-p. In each setting the fluid from blood and dialysate outlet were collected (recipients “cbo” and “cdo”, resp.) for 8 min. To be independent of the machine accuracy of set flow rates, sample volumes were measured by weighing, and effective flow rates of blood Qb_eff and total dialysate Qd_tot_eff were calculated. Samples were taken into monovettes from “cbi”, “cbo” and “cdo”. Urea concentrations cbi, cbo and cdo were determined by sending the samples to two commercial clinical labs who delivered consistent results. Blood and dialysate side urea clearances were calculated as KUB= Qb_eff*(cbi-cbo)/cbi and KUD=Qd_tot_eff*cdo/cbi. Results The table in Fig. 1 includes the measure values of Qb_eff and Qd_tot_eff for each setting. Blood and dialysate outlet concentrations (cbo and cdo, resp.) and calculated blood and dialysate side clearances are shown in Fig. 2. Lab results in repeated settings were highly reproducible with a SD < 2 mg/dL. Switching from hfHD to oHDF-p at equal Qd_tot always decreased cbo, corresponding to a higher clearance in oHDF-p. Reducing total dialysate flow from 400 to 300 ml/min caused a slight decrease in clearance in both modalities. KUB and KUD were in good agreement, showing that urea mass balance was well controlled in the experiment. Conclusion The educational bench model demonstrates the superior low molecular clearance of oHDF-p compared to hfHD at equal Qd_tot, reflected by lower urea cbo values in oHDF-p. Although the clinical outcome advantage of oHDF-p is rather related to middle molecular clearance, the model shows that the improved treatment quality of oHDF-p can be provided with no extra resource utilization compared to hfHD, and that dialysis adequacy as measured by urea clearance is even increased despite of the fact that a part of Qd_tot is deviated as substitution fluid. As moderately reducing Qd_tot in many cases only results in acceptable clearance reductions, the automated adjustment of both dialysate and substitution flow rates for oHDF-p could improve patient outcome at even reduced resource utilization.

#1813 Safety and efficacy of reducing hemodialysis fluid flow rate—contribution to planetary health

Abstract Background and Aims Historically, increasing dialysate flow rates (Qd) have been recommended to improve hemodialysis (HD) efficiency. For decades, Qd has routinely been set to a fixed rate of 500 ml/min. A standard HD treatment uses on average around 500 L of water [1], resulting in a consumption of 78 000 L per patient and year with an additional estimated 10 000 L for post-dilution hemodiafiltration. This corresponds to the annual water consumption of 1.5 persons in developed countries and considerably more in developing countries. We investigated the effect of reducing dialysate flow rates on HD safety and efficacy. Method This is a prospective single-center non-blinded observational study. We investigated the effect of a 1:1 adjustment of online Qd to blood flow rate by adjusting autoflow (AF) settings of the dialysis monitor to a calculation factor of 1.0 with a lower Qd limit of 350 ml/min (AF 1.0 mode). We examined the effect on dialysis efficacy, metabolic markers, and anemia in routine biochemical analyses, and calculated energy, water, and waste savings in 116 stable chronic HD patients. Data were compared with previous turnover in energy, waste, and water, as well as with clinical results prior to the mentioned modifications. Results After 12 months of HD treatment with AF 1.0 mode we observed reductions of 10% in electricity consumption, 19% in raw water consumption, and 24% in dialysate concentrate consumption. Conversely, we did not observe deteriorations in treatment quality or dialysis dose (Table 1), nor phosphate or hemoglobin. Conclusion Long-term HD treatment with reduced dialysate fluid flow rates led to substantially improved water and carbon footprints with potential effects on planetary health and economic savings, while dialysis quality remained unchanged.

Does online high-volume hemodiafiltration offer greater efficiency and sustainability compared to high-flux hemodialysis? A detailed simulation analysis anchored in real-world data

Abstract Recent findings, including the CONVINCE study report, suggests the superiority of high-volume hemodiafiltration over high-flux hemodialysis in improving patients’ outcomes. Despite positive patient outcomes, concerns have arisen about the potential negative environmental impact of high-volume hemodiafiltration, as it may lead to increased water and dialysis fluid consumption and higher waste production. In this manuscript, we address the environmental impact of high-volume HDF, focusing on three key factors: water treatment consumption, dialysis fluid consumption, and solute efficiency markers of HD and HDF. By optimizing HDF prescription through adjustments in operational capabilities, such as reducing the QD/QB ratio to 1,2 rather than 1,5 and incorporating automated ultrafiltration and substitution control, it has been demonstrated that HDF delivers a higher dialysis dose for small and middle-molecule uremic compounds with the same dialysis fluid consumption and at equal dialysis doses dialysis fluid consumption is reduced. This finding is supported by real-world data from 26 031 patients who underwent high-volume postdilution hemodiafiltration at a reduced dialysis flow (550 ml/min) and achieved an effective OCMKt/V of 1.70. In addition, simulation modeling calculations, using blood extraction coefficient, dialysate saturation coefficient, and solute clearances with urea (small MW) and ß2M (middle MW), consistently show postdilution HDF's superiority to HD. This holds true even with a significant reduction in dialysis flow down to 440 ml/min reflecting QD/QB ratio of 1,2. Postdilution HDF generates high ultrafiltrate flow (up to 35% of blood flow), delivering saturated ultrafiltrate to the lower solute concentration containing effluent dialysate, thus enhancing solute clearance which opens the way to reduce the dialysis flow. In conclusion, our analysis, combining simulation and real-world data, suggests that postdilution HDF could be a more environmentally friendly treatment option compared to conventional hemodialysis. Additionally, automated user-friendly functions that minimize dialysis fluid use, can further strengthen this environmental benefit while enhancing efficiency.

Kinetics of β -2-Microglobulin with Hemodiafiltration and High-Flux Hemodialysis.

A kinetic model for beta-2-microglobulin removal and generation was used to explore the impact of adding hemodiafiltration on predialysis and time-averaged serum values. The model was tested on data from the HEMO study and on a sample of patients undergoing high-flux hemodialysis. The impact of hemodiafiltration on beta-2-microglobulin levels was evaluated by modeling four randomized studies of hemodiafiltration vs. hemodialysis. The impact of residual kidney function on beta-2-microglobulin was tested by comparing results of previously reported measured data with model predictions. In the low-flux and high-flux arms of the HEMO study, measured median beta-2-microglobulin reduction ratios could be matched by dialyzer clearances of 5.2 and 26 ml/min, respectively. Median pre-dialysis serum beta-2-microglobulin levels were matched if generation rates of beta-2-microglobulin were set to approximately 240 mg/day. In another group of patients treated with dialyzers with increased beta-2-microglobulin clearances, measured cross-dialyzer clearances (57±28 ml/min) were used as inputs. In these studies the kinetic model estimates of intradialysis and early postdialysis serum beta-2-microglobulin levels were similar to median measured values. The model was able to estimate the changes in pre-dialysis serum beta-2-microglobulin in each of four published randomized comparisons of hemodiafiltration with hemodialysis, although the model predicted a greater decrease in predialysis serum beta-2-microglobulin with hemodiafiltration than was reported in two of the studies. The predicted impact of residual kidney clearance on pre-dialysis serum beta-2-microglobulin concentrations was similar to that reported in one published observational study. Modeling predicted that postdilution hemodiafiltration using 25 L/4h replacement fluid would lower serum time-averaged concentration of beta-2-microglobulin by about 18.2%, similar to the effect of 1.50 ml/min residual kidney glomerular filtration rate. A two-pool kinetic model of beta-2-microglobulin yielded values of reduction ratio and pre-dialysis serum concentration that were consistent with measured values with various hemodiafiltration and hemodialysis treatment regimens.

Most recently developed polyester polymer alloy dialyzer: A new medium cut-off membrane?

New versions of the polyester polymer alloy (PEPA) membrane have appeared over the years, with increases in both the pore size and the amount of polyvinylpyrrolidone (PVP) to optimize hydrophilicity performance. This study aimed to assess the efficacy of the most recently developed PEPA dialyzer, the FDY series, in hemodialysis (HD) modality in terms of uremic toxin removal and albumin loss and to compare it with that of several high-flux dialyzers currently used in HD and post-dilution hemodiafiltration (HDF) treatments. A prospective study was carried out in 21 patients. All patients underwent six dialysis sessions with the same routine dialysis parameters; only the dialyzer and/or the dialysis modality varied: FX80 in HD, FDY 180 in HD, Clearum HS17 in HDF, Elisio 19H in HDF, Vitapes 180 in HDF, and FX80 in post-dilution HDF. The reduction ratios (RR) of urea, creatinine, ß2 -microglobulin, myoglobin, κFLC, prolactin, α1 -microglobulin, α1 -acid glycoprotein, λFLC, and albumin were compared intraindividually. Dialysate albumin loss was also measured. Both membranes FDY and FX80 are high-flux dialyzers and are applied here in high-flux HD. The average RR of β2 -microglobulin was slightly lower in the two HD treatments than in the HDF treatments. Comparison of dialysis treatments revealed that the PEPA FDY dialyzer in the HD modality was more effective than the FX80 dialyzer in high-flux HD and was as effective as post-dilution HDF, especially in terms of myoglobin, κFLC, prolactin, α1 -microglobulin, and λFLC RRs. The FDY treatments obtained similar albumin RR in blood and slightly higher dialysate albumin loss, although the values were clinically acceptable. The most recently developed PEPA dialyzers in the HD modality were as effective as all treatments in the HDF modality and were clearly superior to high-flux helixone HD treatment. These results confirm that this dialyzer should be categorized within the medium cut-off (MCO) membrane classification.

Prospective randomised crossover trial comparing mixed and post-dilution haemodiafiltration: COMPare HDF study

Prospective randomised crossover trial comparing mixed and post-dilution haemodiafiltration: COMPare HDF study

Comparison of the medium cutoff dialyzer and postdilution hemodiafiltration on the removal of small and middle molecule uremic toxins.

The medium cutoff (MCO) dialyzer increases the removal of several middle molecules more effectively than high-flux hemodialysis (HD). However, comparative data addressing the efficacy and safety of MCO dialyzers vs. postdilution hemodiafiltration (HDF) in Korean patients are lacking. Nine patients with chronic HD were included in this pre-post study. Patients underwent HD with an MCO dialyzer for 4 weeks, followed by a 2-week washout period using a high-flux dialyzer to minimize carryover effects, and then turned over to postdilution HDF for 4 weeks. Reduction ratios and differences in the uremic toxins before and after dialysis were calculated from the MCO dialysis, postdilution HDF, and high-flux HD. In the in vitro study, EA.hy926 cells were incubated with dialyzed serum. Compared to postdilution HDF, the MCO dialyzer achieved significantly higher reduction ratios for larger middle molecules (myoglobin, kappa free light chain [κFLC], and lambda FLC [λFLC]). Similarly, the differences in myoglobin, κFLC, and λFLC concentrations before and after the last dialysis session were significantly greater in MCO dialysis than in postdilution HDF. The expression of Bax and nuclear factor κB was decreased in the serum after dialysis with the MCO dialyzer than with HDF. Compared with high-volume postdilution HDF, MCO dialysis did not provide greater removal of molecules below 12,000 Da, whereas it was superior in the removal of larger uremic middle molecule toxins in patients with kidney failure. Moreover, these results may be expected to have an anti-apoptotic effect on the human endothelium.

#3944 COMPARISON OF CLINICAL PERFORMANCE AND HEMOCOMPATIBILITY OF DIALYZERS APPLIED DURING POST-DILUTION ONLINE HEMODIAFILTRATION (HDF) – EMPORA III STUDY

Abstract Background and Aims Performance and hemocompatibility are the two main functions of a hemodialyzer. Synthetic dialysis membranes made from polysulfone (PSU) or polyethersulfone (PES) are mainly used for dialysis treatments and are blended with the hydrophilic agent polyvinylpyrrolidone (PVP), to improve hemocompatibility during dialysis treatments. A novel PSU-based dialyzer (FX CorAL) with an increased and stabilized PVP content has been developed and has shown strong performance and a favourable hemocompatibility profile within previous short term clinical studies. In the present clinical study, we now investigated the performance and hemocompatibility of the FX CorAL vs. two comparators over a longer follow-up time and applied an extended panel of hemocompatibility biomarkers. This allowed us to analyse treatment-specific performance as well as an extensive intra- and interdialytic hemocompatibility profile. Method eMPORA III was a prospective, open, controlled, multicentre crossover trial with randomized treatment sequences conducted in DE, CZ and HU. It randomized stable patients receiving regular post-dilution online HDF to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun), each for 4 weeks. The primary outcome was β2-m removal rate (RR) during 4 hrs HDF. Non-inferiority (margin: 5%) and superiority of FX CorAL 600 versus comparators were tested at α = 2.5% (one-sided), with adjustment for multiple tests. Secondary endpoints were RR and/or clearance of β2-m and other molecules, as well as intra- and interdialytic changes of markers of complement activation (C3a, sC5b-9), cell activation / inflammation (white blood cells (WBC), PMN elastase, IL-6, IL-8, LTB-4, sICAM-1, hsCRP), platelet activation (platelet count, β-TG, TxB-2), and oxidative stress (MDA, GSH-Px). Intradialytic hemocompatibility markers were analysed descriptively as differences vs. the values determined at the start of the HDF session (LS means). Results Eighty-two patients were included and analysed in the safety population, with n = 76 presenting data for the primary outcome (ITT population). FX CorAL 600 showed the highest β2-m RR (LS mean: 76.31%), followed by FX CorDiax 600 (75.71%) and xevonta Hi 15 (74.49%). Non-inferiority to its comparators was statistically significant (p<0.0001 each). Superiority was shown vs. xevonta Hi 15 (p<0.0001), but not vs. FX CorDiax 600 (p = 0.0606). The secondary endpoints β2-m clearance as well as myoglobin clearance and RR affirmed these results; small molecule clearances and/or RR were similar between dialyzers. Analyses of hemocompatibility markers within one HDF session, found the following significant differences: Complement activation • C3a 15 min: FX CorAL: 31%; FX CorDiax: 59% (p = 0.003 vs. FX CorAL); xevonta: 41% (p = 0.029 vs. FX CorAL) • sC5b-9 60 min: FX CorAL: 24%; FX CorDiax: 25% (p = 0.337); xevonta: 41% (p<0.0001) Cell activation/ Inflammation • WBC 15 min: FX CorAL: -7.7%; FX CorDiax: -11.1% (p = 0.015); xevonta: -10.1% (p = 0.246) • Monocytes 15 min: FX CorAL: -30.9%; FX CorDiax: -30.3% (p = 0.533); xevonta: -38.2% (p = 0.012) • Neutrophils 15 min: FX CorAL: -3.0%; FX CorDiax: -7.5% (p = 0.019); xevonta: -6.1% (p = 0.258) • PMN elastase 60 min: FX CorAL: 18%; FX CorDiax: 42% (p = 0.003); xevonta: 52% (p = 0.0003) • LTB-4 15 min: FX CorAL: 170%; FX CorDiax: 217% (p = 0.047); xevonta: 186% (p = 0.539) Platelet activation • β-TG 60 min: FX CorAL: -15%; FX CorDiax: 4% (p<0.0001); xevonta: 18% (p<0.0001) Hemocompatibility markers showed no interdialytic changes, i.e., no significant changes within treatment periods. Nine serious adverse events occurred in this study, none of which was dialyser related. Conclusion FX CorAL 600 efficiently removed middle and small molecules and was non-inferior to both comparators and significantly superior to xevonta Hi 15 in β2-m RR. The typical drop in WBC, monocyte, and neutrophil count during dialysis as well as the rise of complement (C3a, sC5b-9) and cell / platelet activation markers (PMN elastase, LTB-4 and β-TG) were lower or comparable during treatment with FX CorAL vs. both comparators, indicating superior hemocompatibility properties.

Removal of Middle Molecules and Dialytic Albumin Loss: A Cross-over Study of Medium Cutoff and High-Flux Membranes with Hemodialysis and Hemodiafiltration.

Key Points HDF and MCO have shown greater clearance of middle-size uremic solutes in comparison with HF dialyzers; MCO has never been studied in HDF.MCO in HDF does not increase the clearance of B2M and results in a higher loss of albumin. Background Middle molecule removal and albumin loss have been studied in medium cutoff (MCO) membranes on hemodialysis (HD). It is unknown whether hemodiafiltration (HDF) with MCO membranes provides additional benefit. We aimed to compare the removal of small solutes and β2-microglobulin (B2M), albumin, and total proteins between MCO and high-flux (HFX) membranes with both HD and HDF, respectively. Methods The cross-over study comprised 4 weeks, one each with postdilutional HDF using HFX (HFX-HDF), MCO (MCO-HDF), HD with HFX (HFX-HD), and MCO (MCO-HD). MCO and HFX differ with respect to several characteristics, including membrane composition, pore size distribution, and surface area (HFX, 2.5 m2; MCO, 1.7 m2). There were two study treatments per week, one after the long interdialytic interval and another midweek. Reduction ratios of vitamin B12, B2M, phosphate, uric acid, and urea corrected for hemoconcentration were computed. Dialysis albumin and total protein loss during the treatment were quantified from dialysate samples. Results Twelve anuric patients were studied (six female patients; 44±19 years; dialysis vintage 35.2±28 months). The blood flow was 369±23 ml/min, dialysate flow was 495±61 ml/min, and ultrafiltration volume was 2.8±0.74 L. No significant differences were found regarding the removal of B2M, vitamin B12, and water-soluble solutes between dialytic modalities and dialyzers. Albumin and total protein loss were significantly higher in MCO groups than HFX groups when compared with the same modality. HDF groups had significantly higher albumin and total protein loss than HD groups when compared with the same dialyzer. MCO-HDF showed the highest protein loss among all groups. Conclusions MCO-HD is not superior to HFX-HD and HFX-HDF for both middle molecule and water-soluble solute removal. Protein loss was more pronounced with MCO when compared with HFX on both HD and HDF modalities. MCO-HDF has no additional benefits regarding better removal of B2M but resulted in greater protein loss than MCO-HD.

Systematic Comparison of Uremic Toxin Removal Using Different Hemodialysis Modes: A Single-Center Crossover Prospective Observational Study

Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group. Twenty-six patients were treated by those three techniques of extra renal epuration. Mean Kt/Vurea was not different between the treatment methods. Mean reduction ratio of beta2microglobulin was significantly higher for both HDF treatments than for HD (p < 0.001). Myoglobin, kappa, and lambda free light chain reduction ratio was significantly different between the modes: 37.75 ± 11.95%, 45.31 ± 11% and 61.22 ± 10.56%/57.21 ± 12.5%, 63.53 ± 7.93%, and 68.40 ± 11.79%/29.12 ± 8.44%, 34.73 ± 9.01%, and 45.55 ± 12.31% HD, preHDF, and postHDF, respectively (p < 0.001). Mean protein-bound solutes reduction ratio was not different between the different treatments except for PCS with a higher reduction ratio during HDF treatments. Mean albumin loss was always less than 2 g. HDF improved removal of middle molecules but had no effect on indoles concentration without any difference between synthetic dialysis membranes.

What Is the Difference between Post- and Pre-Dilution in On-Line Haemodiafiltration in the Removing of Median-Molecular-Weight Toxins?

Introduction: β2-microglobulin and prolactin are medium-molecular-weight toxins. We believe that the rate of removal of these molecules, using filters with two different surfaces, in post- and pre-dilution haemodiafiltration, will be of interest to the literature. Methods: We studied, in 12 haemodialyzed patients, the removal of those, with filter with surface of 2.5 m2 (Group A) or 2.1 m2 (Group B) with post-dilution haemodiafiltration, and with a filter with surface 2.5 m2 with pre-dilution (Group C). Results: Satisfactory removal of β2-microglobulin (best with post-dilution) was found, and a good rate of removal of prolactin without the filter surface played a role in both cases. Conclusion: The elimination of β2-microglobulin in post-dilution is not affected by the filter surface area. Pre-dilution achieves removal of β2-microglobulin, less than that of post-dilution. Prolactin was removed satisfactorily regardless of the filter surface in post-dilution, and its removal appears to be less than that of β2-microglobulin.

The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins.

The accumulation of protein-bound uremic toxins (PBUT) is associated with increased cardiovascular outcomes in patients on dialysis. However, the efficacy of PBUT removal for a medium-cutoff (MCO) membrane has not been clarified. This study was designed to assess the efficacy of PBUT clearance according to dialysis modalities. In this prospective and cross-over study, we enrolled 22 patients who received maintenance hemodiafiltration (HDF) thrice weekly from three dialysis centers. The dialysis removal of uremic toxins, including urea, beta 2-microglobulin (B2MG), lambda free light chain (λ-FLC), indoxyl sulfate (IS), and p-cresyl sulfate (pCS), was measured in the 22 patients on high-flux HD (HF-HD), post-dilution online HDF (post-OL-HDF), and MCO-HD over 3 weeks. The average convection volume in post-OL-HDF was 21.4 ± 1.8 L per session. The reduction rate (RR) of B2MG was higher in post-OL-HDF than in MCO-HD and HF-HD. The RR of λ-FLC was the highest in MCO-HD, followed by post-OL-HDF and HF-HD. The dialysate albumin was highest in MCO-HD, followed by post-OL-HDF and HF-HD. Post-dialysis plasma levels of IS and pCS were not statistically different across dialysis modalities. The total solute removal and dialytic clearance of IS and pCS were not significantly different. The clearance of IS and pCS did not differ between the HF-HD, post-OL-HDF, and MCO-HD groups.

Water-Soluble Vitamins and Trace Elements Losses during On-Line Hemodiafiltration.

Maintenance hemodialysis induces water-soluble vitamins and trace elements losses, which is why recommendations regarding potential supplementation were provided, but mainly based on conventional hemodialysis. This study′s aim was to measure the water–soluble vitamins and trace element losses during one on-line post-dilution hemodiafiltration (HDF) session. Thirty-nine patients under maintenance HDF were enrolled. We used the Theraflux® sampler (Theradial Corp., Orvault, France) to analyze the full session dialysate mass transfer. Blood and dialysate samples were collected before and after one HDF session to measure B1, B2, B6, B9, B12, C vitamins, zinc, and selenium concentrations. Values significantly decreased for B1 (20.2%), B2 (13%), B6 (25.4%), B9 (32.6%), C (66.6%) and selenium (6.7%). No significant differences were found for vitamin B12 and zinc. The dialysate losses per session were 1.12 ± 0.88 mg for vitamin B1, 0.28 ± 0.30 mg for B2, 0.33 ± 0.09 mg for B6, 0.3 ± 0.18 mg for B9, 147.5 ± 145.50 mg for C and 25.75 ± 6.91 mg for zinc. Vitamin B12 and selenium were under detection values. In conclusion, during a standard 4hr-HDF session, we found important losses for vitamin B1, B6, B9, C and zinc, suggesting the need for regular monitoring of plasma levels and systematic supplementation of these compounds.

Basic physics of hemodiafiltration.

Standard high-flux hemodialysis (HD) clears urea very efficiently but is less efficient at clearing uremic toxins with larger molecule size, which diffuse more slowly. Hemodiafiltration (HDF) provides much higher convection rates, thereby reliably increasing the clearance of these larger toxins. However, the high ultrafiltration volumes employed by HDF significantly increase the concentration of proteins and lipids in the dialyzer blood compartment. This has the effect of increasing plasma viscosity, which opposes solute diffusion, and increasing plasma oncotic pressure, which opposes convection. The negatively charged plasma proteins also influence the equilibration of ions between dialysate and blood compartments. These effects result in varying conditions for solute transport along the length of the dialyzer and along the radial distance from the membrane within the dialyzer fibers. High-flux dialyzers can be designed to augment solute diffusion and internal filtration, so that their performance approaches that of HDF. This avoids some of the mechanical complexity of HDF, but such enhanced dialyzers may be more difficult to manufacture, control and monitor. Here, we present and discuss the most important physical phenomena associated with HDF therapy, providing an overview of its main concepts and principles. In particular, we discuss the physics of solute diffusion and convection and the factors affecting them, and we compare predilution or postdilution HDF with enhanced HD.

High-Volume Hemodiafiltration and Cool Hemodialysis Have a Beneficial Effect on Intradialytic Hemodynamics: A Randomized Cross-Over Trial of Four Intermittent Dialysis Strategies

IntroductionCompared to standard hemodialysis (S-HD), postdilution hemodiafiltration (HDF) has been associated with improved survival.MethodsTo assess whether intradialytic hemodynamics may play a role in this respect, 40 chronic dialysis patients were cross-over randomized to S-HD (dialysate temperature [Td] 36.5 °C), cooled HD (C-HD; Td 35.5 °C), and HDF (low-volume [LV-HDF)] and high-volume [HV-HDF], both Td 36.5 °C, convection volume 15 liters, and at least 23 liters per session, respectively), each for 2 weeks. Blood pressure (BP) was measured every 15 minutes. The primary endpoint was the number of intradialytic hypotensive (IDH) episodes per session. IDH was defined as systolic BP (SBP) less than 90 mmHg for predialysis SBP less than 160 mmHg and less than 100 mmHg for predialysis SBP greater than or equal to 160 mmHg, independent of symptoms and interventions. A post hoc analysis on early-onset IDH was performed as well. Secondary endpoints included intradialytic courses of SBP, diastolic BP (DBP) and mean arterial pressure (MAP).ResultsDuring S-HD, IDH occurred 0.68 episodes per session, which was 3.2 and 2.5 times higher than during C-HD (0.21 per session, P < 0.0005) and HV-HDF (0.27 per session, P < 0.0005), respectively. Whereas the latter 2 strategies showed similar frequencies, HV-HDF differed significantly from LV-HDF (P = 0.02). A comparable trend was observed for early-onset IDH: S-HD (0.32 per session), C-HD (0.07 per session, P < 0.0005) and HV-HDF (0.10 per session, P = 0.001). SBP, DBP, and MAP declined during S-HD (−6.8, −5.2, −5.2 mmHg per session; P = 0.004, P < 0.0005, P = 0.002 respectively), which was markedly different from C-HD (P < 0.01).ConclusionThough C-HD and HV-HDF showed the lowest IDH frequency and the best intradialytic hemodynamic stability, all parameters were most disrupted in S-HD. Therefore, the survival benefit of HV-HDF over S-HD may be partly caused by a more beneficial intradialytic BP profile.

Comparison of four medium cut-off dialyzers.

Recently, several pharmaceutical companies have developed new medium cut-off (MCO) dialyzers for expanded hemodialysis (HDx). This study aimed to compare the safety and efficacy of four MCO dialyzers, against each other and versus high-flux hemodialysis (HD) and post-dilution hemodiafiltration (HDF). A prospective study was carried out on 23 patients who underwent six dialysis sessions: two sessions with the FX80 Cordiax in HD and HDF, and four HDx sessions with the Phylther 17-SD, Vie-18X, Elisio HX19 and Theranova 400 dialyzers. The reduction ratios (RRs) of urea, creatinine, β2-microglobulin, myoglobin, kappa free immunoglobulin light chain (κFLC), prolactin, α1-microglobulin, α1-acid glycoprotein, lambda (λFLC) and albumin were compared. Dialysate albumin loss was also measured. The differences in efficacy between the evaluated dialyzers were minimal in small molecules and even up to the size of β2-microglobulin. The main differences were found between myoglobin, κFLC, prolactin, α1-microglobulin and λFLC RRs, in which all four MCO dialyzers, with similar efficacy, were clearly superior to HD and slightly inferior to HDF treatment. Albumin losses in the dialysate with HD dialyzers were <1 g and between 1.5 and 2.5 g in HDx and HDF. The global removal score values were similar in all four HDx treatments, and again significantly higher than those with HD. The results of the four MCO dialyzers evaluated in this study showed good efficiency, with no significant performance differences between them while being completely safe in terms of albumin loss. Likewise, the study confirms the superiority of HDx over high-flux HD with an efficacy close to that of post-dilution HDF.

Efficacy and Safety of the Medium Cut-Off Elisio HX Dialyzer

Introduction: The medium cut-off Elisio HX dialyzer by Nipro became commercially available in Europe in 2021, but there are still no reports of in vivo data. This study aimed to evaluate the safety and efficacy of it compared with previously evaluated hemodialysis (HD), expanded HD (HDx), and postdilution hemodiafiltration (HDF) treatments. Methods: A prospective study was carried out on 18 patients who underwent 5 dialysis sessions: FX80 Cordiax in HD, Elisio H19 in HD, Elisio HX19 in HDx, Theranova 400 in HDx, and FX80 Cordiax in HDF. The reduction ratios of urea, creatinine, ß₂-microglobulin, myoglobin, kappa FLC, prolactin, α₁-microglobulin, α₁-acid glycoprotein, lambda FLC, and albumin were compared. Dialysate albumin loss was measured. Results: The comparison between the different dialysis modalities revealed no difference for small molecules, but HDx and HDF were significantly more efficient than HD for medium and large molecule removal. The efficacy of Elisio HX19 dialyzer in HDx was similar to the Theranova 400, superior to both dialyzers in HD, and slightly lower than HDF. Albumin losses in dialysate with HD dialyzers were less than 1 g, but between 1.5 and 2.5 g in HDx and HDF. The global removal score (GRS) values with HDx treatments were statistically significantly higher than those with HD. The highest GRS was obtained with the helixone dialyzer in HDF. Conclusions: The new MCO dialyzer, Elisio HX, performs with excellent behavior and tolerance. It represents an upgrade compared to their predecessor and is very close to the removal capacity of HDF treatment.

MO642: Comparison of Medium Cut-Off Dialyzer and Post-Dilution Hemodiafiltration on the Removal of Small and Middle Molecule Uremic Toxins

Abstract BACKGROUND AND AIMS The medium cut-off (MCO) dialyzer increases the removal of several middle molecules more effectively than high-flux hemodialysis (HD). However, there are no comparable data on the efficacy and safety of MCO dialyzers versus post-dilution hemodiafiltration (HDF) in Korean patients. METHOD A total of 9 patients with chronic HD were included in this crossover study. Patients received HD with an MCO dialyzer for 4 weeks, followed by a 2-week washout period, using a high-flux dialyzer to minimize carry-over effects and then crossed over to post-dilution HDF for 4 weeks. Reduction ratios and differences in the values before and after were calculated from the MCO dialysis, post-dilution HDF and high-flux HD. In the in vitro study, EA.hy926 cells were treated with dialyzed serum. RESULTS Compared with post-dilution HDF, the MCO dialyzer achieved significantly higher reduction ratios for larger middle molecules [myoglobin, kappa free light chain (κFLC) and lambda FLC (λFLC)]. Similarly, the differences between before and after the last dialysis session of myoglobin, κFLC, and λFLC were significantly greater in MCO dialysis than in post-dilution HDF. The expression of Bax and nuclear factor-κb was decreased in the serum after dialysis with the MCO dialyzer than with HDF. CONCLUSION Compared with high-volume post-dilution HDF, MCO dialysis showed no differences in the removal of molecules below 12 000 Da, whereas it was superior in the removal of larger uremic middle molecule toxins in patients with kidney failure. Moreover, these results might be expected to have an anti-apoptotic effect on the human endothelium.

MO647: Novel Medium Cut-Off Membranes in Larger Medium Molecules Removal, How Far Can We Go?

Abstract BACKGROUND AND AIMS Dialysis with medium cut-off membranes (MCO) are growing fast during the last years thanks to the availability of an always-increasing number of membranes capable of reaching elevated clearance levels of medium molecules without significant loss of albumin. These achievements made MCO membranes an appropriate alternative to mixed diffusive-convective techniques which are frequently limited by clinical (low-performance vascular accesses) or social reasons (costs, availability). However, the term ‘medium molecules’ includes a wide spectrum of molecules with major differences in molecular weight (MW–from 0.5 to 60 KDa). Considering the human serum albumin's (HSA) MW of 64.5 KDa as the insuperable cut-off for avoiding unwanted protein loss, whereas there are many studies about clearance of medium molecules with dimensions below 25–30 KDa, fewer data are available about those with MW from 40 to ˃ 60 KDa. In this study, we evaluated the clearance proprieties of a new MCO membrane (Asahi Kasei's ViE-21X®), compared with both haemodiafiltration and hemodialysis (HD) with a well-known medium cut-off membrane (Baxter's Theranova 400®-Th400), of three medium molecules with increasing MW: free kappa chains (K-FLC 22.5 KDa), free lambda chains (L-FLC 45 KDa) and alpha-1 antitrypsin (A1AT 52–54 KDa) and measured albumin loss amount. METHOD We evaluated 12 patients chronically dialyzed three times a week in our Centre with mixed or post-dilutional haemodiafiltration (HDF) with various membranes. We collected blood samples before and after a common HDF session after a short interdialytic period for K-FLC, L-FLC, A1AT and HSA. Then, we collected the same data for two more sessions after a short interdialytic period conducted only with diffusive techniques, one using Th 400 and another with ViE-21X. For all molecules, we evaluated reduction ratio ± standard deviation (RR ± SD) while statistical significance (P &amp;lt; .05) was examined with Student's t-test. All data were adjusted by dialysis length, membranes surface area, blood flow rate and ultrafiltration rate avoiding any significant difference. RESULTS ViE-21X demonstrated an increased RR of K- and L-FLC compared with HDF and Th 400 even without reaching a statistical significance (38.82 ± 14.53% for K-FLC versus 32.36 ± 22.62% and 30.58 ± 24.10% respectively for HDF and Th400; P = .10 versus HDF, P = 0.13 versus Th 400. 35.63 ± 14.30% for L-FLC versus 30.48 ± 22.51% and 29.36 ± 24.91% respectively of HDF and Th 400; P = .19 versus HDF, P = 0.18 versus Th 400). Both ViE-21X and Th 400 showed higher RR for the largest molecule, A1AT, compared with HDF, reaching statistical significance (24.66 ± 19.98% for ViE-12X and 24.67%±20.15% for Th 400 versus 18.46% ± 21.73% for HDF, P &amp;lt; .05 for both). None of the techniques showed a significant loss of albumin, even if Th 400 showed a slightly greater loss compared to HDF and ViE-21X (2.59%±5.40% for HDF, 6.31%±23.61% for Th 400, 2.58%±24.24% for ViE-21X P = NS) (Figure). CONCLUSION Our data confirmed that studied MCO membranes can be an effective alternative to HDF in the clearance of medium molecules without any remarkable loss of albumin. Indeed, compared with HDF, they showed non-inferiority clearance levels for K- and L-LFC and a statistically significant benefit in the clearance of the studied largest one, A1AT, which has a close MW to HSA. Furthermore, according to our data, novel MCO membrane ViE-21X seems to show further benefits compared to other membranes. More studies with larger populations need to be conducted to confirm these data.

MO654: Automatic KUF Max Determination as a Tool to Prescribe a Personalized Convection Flow in Post-Dilution Haemodiafiltration by Predicting the Transmembrane Pressure to Which the System will be Subjected

Abstract BACKGROUND AND AIM Post-dilutional haemodiafiltration (HDF) with high convection volumes are suggested to improve survival. However, a large increase in convection flow (QUF) is associated with high transmembrane pressure (TMP) which, when exceeding limits advised by guidelines, acts as a limiting factor and prevents achieving the prescription. Our aim is to predict the TMP needed to reach any given convection flow for a patient and dialysis session. METHOD The TMP necessary to obtain a desired convection was predicted from the automatic determination of the maximum ultrafiltration coefficient (KUF max, HDF machine Dialog iQ, BBraun, Melsungen, Germany) and compared to the actual value for 16 patients and 29 dialysis sessions. KUF max was determined at the start of the session and the coefficients of the quadratic regression of the ultrafiltration coefficient (KUF) on convection flow (KUF = a*(QUF)² + b* QUF + c) were obtained and used to predict the TMP needed to obtain a convection of 30% of QB (QUF max), knowing that TMP = QUF/KUF. Then, infusion rate was set at QUF max and the observed TMP was recorded after 8 minutes stabilization. Dialyses were performed with the patient's usual dialyzer (Diacap pro for 28 sessions, Nephral 400 for 1 session) and blood flow [363 ± 30 mL/min (300–400 mL/min)]. Observed and estimated TMPs were compared. RESULTS There was a high correlation between both TMPs (Pearson's R = 0.98; P &amp;lt; .01). The Bland and Altman analysis showed an average difference (systematic bias) of 3.3% with 95% limits of agreement of −9 and +15% and a maximal difference of 12%, indicating a slight overestimation. CONCLUSION KUF max determination allows estimating TMP at any QUF prescription with an acceptable error (3%). Therefore, the KUF on QUF parabolic curve may be of help in the clinical setting to prescribe the most suitable convection in post-dilutional HDF by predicting the TMP the filtrating system will be submitted to. Based on this principle, automatic systems to aid personalized convection flow prescriptions can be developed.