Comparison of 2 medium cutoff dialyzers versus on-line hemodiafiltration regarding depurative ability and albumin loss: An uncontrolled clinical research.

BACKGROUND: Hemodialysis (HD) techniques that best remove molecules in the middle to high molecular weight range are on-line hemodiafiltration (OL-HDF) and HD with medium cut-off (MCO) membranes. The aim of this study was to compare efficacy and safety of OL-HDF with FxCordiax HDF 800™, with HD with 2 MCO dialyzers: Theranova 500® and the new Elisio 21HX™ dialyzer. METHODS: Fourteen patients following treatment with OL-HDF using FxCordiax HDF 800™ were randomized to receive a consecutive 1-week HD treatment with Theranova 500® and Elisio 21HX™.The reduction rate (RR) of differently sized molecules was compared, as well as the variation rate in molecules smaller than 1000, detected by nuclear magnetic resonance based chemometrics (metabolomics). Albumin loss in dialysate was quantified. RESULTS: Lower RRs were found for molecules around 20 000 with Elisio 21HX™ compared to OL- HDF (RR prolactin 58.5% versus 66.7%, p = 0.034; RR Kappa light chain 63.1% versus 71.8%, p = 0.010). Albumin loss per session was higher with Theranova 500® than with OL-HDF and with Elisio 21HX™ (2249.9 ± 714.1 mg, 815.2 ± 474.0 mg, 442.9 ± 135.9 mg, p < 0.001, respectively). Metabolomic studies suggested, by semi-quantitative analysis, a greater depurative capacity of OL-HDF, followed by Elisio 21HX™, and then Theranova 500®. CONCLUSIONS: In this study, HD with Theranova 500® has proven to be very similar in efficacy to OL-HDF, although with a significantly higher albumin loss. HD with Elisio 21HX™ resulted in lower removal of molecules around 20 000 compared to OL-HDF, with no significant difference compared to Theranova 500®, and with less albumin loss than Theranova 500®.

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.

Improved ß2-Microglobulin and Phosphorous Removal with Expanded Hemodialysis and Online Hemodiafiltration versus High-Flux Hemodialysis: A Cross-Over Randomized Clinical Trial.

INTRODUCTION: Expanded hemodialysis (HDx) is expected to provide enhanced permeability of medium-sized molecules, selective solute retention, and better internal retrofiltration. The primary objective of this study was to compare the efficiency for removal of ß2-microglobulin with 3 different extracorporeal therapies (ETs): high-flux hemodialysis (HF), online hemodiafiltration (OL-HDF), and HDx. The secondary objective was to evaluate the efficiency of removal of other uremic toxins, including urea, phosphate, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-cresol. METHODS: This single-center, randomized, and cross-over study was performed. Patients were randomized to determine the initial modality of treatment, each period lasted 4 weeks and between one modality and another, there was a washout period of 1 week. Reduction ratios (RRs) of different-size molecules and albumin were calculated for the different ET. RESULTS: Twenty-two patients were included, ß2-microglobulin RR was greater during both OL-HDF and HDx as compared to HF (RR 62% vs. 73% vs. 27%, respectively, p = <0.0001), and there was no significant difference between HDx and OL-HDF (p = 0.09). A decrease in serum phosphate levels was observed in the HDx and OL-HDF periods, contrary to an increase in HF (-0.79 mg/dL vs. -1.02 mg/dL vs. + 0.11 mg/dL, respectively, p = <0.0001). There was no difference in RRs of other molecules (BUN, CRP, IL-6, IL-10, TNF-⍺, indoxyl sulfate, and p-Cresol). There was no decrease in serum albumin in any ET. CONCLUSION: HDx provides enhanced removal of ß2-microglobulin and phosphate as compared to HF, and similar efficacy as with OL-HDF. HDx should be considered an alternative to chronic convective therapies.

Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19.

INTRODUCTION: Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19. METHODS: This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, ß2 microglobulin and albumin levels pre/post-dialysis and on 1st-2nd week. We compared levels among both techniques and control group (HD without COVID-19). RESULTS: We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and ß2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group. DISCUSSION: Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave. CONCLUSION: HDx appears to provide better clearance for TNFα and ß2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

Flow Dynamic Analysis by Contrast-Enhanced Imaging Techniques of Medium Cutoff Membrane Hemodialyzer.

INTRODUCTION: Medium cutoff (MCO) membranes represent an interesting innovation in the field of hemodialysis. Given the correlation between large (PM >25 kDa) middle molecules (LMM) and clinical outcomes, the possibility to broaden the spectrum of solutes removed in hemodialysis with MCO membranes introduces a new perspective for end-stage kidney disease patients. Due to low diffusion coefficients of LMM, the use of convection is required to maximize extracorporeal clearance. High convective rates are achieved with high-flux membranes in hemodiafiltration, a technique not available in the US. In case of the MCO membrane, remarkable clearances of LMM are achieved combining the permeability of the membrane with a significant amount of internal convection. The mechanism of filtration-backfiltration inside the dialyzer enables effective removal of LMM in a technique called expanded hemodialysis (HDx). Given such theoretical explanation, it is important to demonstrate the blood and ultrafiltration rheology inside the MCO dialyzer. METHOD: This study for the first time describes flow dynamic parameters and internal cross-filtration, thanks to specific radiology and nuclear imaging techniques. RESULTS: Flow dynamic analysis of the blood and dialysate compartment confirms excellent distribution of velocities and an excellent matching of blood and dialysate. Average blood flow velocity allows for wall shear rates adequate to avoid protein stagnation at the blood membrane interface and increase in blood viscosity. Cross-filtration analysis demonstrates a remarkable filtration/backfiltration flux reaching values >30 mL/min at a blood flow of 300 mL/min and zero net filtration. CONCLUSION: The MCO dialyzer Theranova 400 appears to have a design optimized to perform expanded hemodialysis (HDx).

Use of regional citrate anticoagulation with medium cut-off membrane: pilot report.

BACKGROUND: Regional citrate anticoagulation during hemodialysis provides an immediate and complete anticoagulant effect, which is limited to the extracorporeal circuit. Citrate has become the standard anticoagulant in acute renal replacement therapy and is widely used in various intermittent hemodialysis modalities, especially for patients with contraindications for heparin. With the increased adoption of medium cut-off membranes, experience with regional citrate anticoagulation is needed. To our knowledge, this is the first report to assess the feasibility of regional citrate anticoagulation in expanded hemodialysis. METHODS: We prospectively analyzed 5 expanded hemodialysis procedures in 5 patients in which a medium cut-off membrane (Theranova®) was used. We followed our standard citrate protocol developed and tested for high-flux membrane. Anticoagulation was performed with a continuous infusion of 8% trisodium citrate into the arterial line and supplementation of 1 M calcium chloride into the venous line. We monitored ionized calcium and magnesium, sodium and blood gas analysis. Anticoagulation effectiveness was assessed by post-filter ionized calcium and by visual inspection of the anticoagulation in the circuit. RESULTS: There were no prematurely terminated procedures due to anticoagulation-related complications. With a blood flow of 250 mL/min and a dialysate flow of 500 mL/min, we were able to maintain serum ionized calcium in the range of 0.89-1.29 mmol/L and serum sodium in the range of 136-144 mmol/L. The mean pre- and post-dialysis arterial circuit pH was 7.42 (± 0.04) and 7.53 (± 0.23), respectively. The mean pre- and post-dialysis serum ionized magnesium was 0.54 (± 0.04) mmol/L and 0.43 (± 0.03) mmol/L, respectively (measurements were done on a point-of-care ionometer with a lower normal range for ionized magnesium). CONCLUSION: We have shown that our standard citrate protocol for high-flux hemodialysis membrane could be successfully adopted for use in expanded hemodialysis with a medium cut-off membrane. Overall, electrolyte and acid-base balances were relatively well-controlled and anticoagulation effectiveness was excellent. TRIAL REGISTRATION: This is a pilot report with results taken from a larger ongoing trial (registered at ClinicalTrials.gov on October 25, 2019 under number NCT04139525) comparing citrate and heparin anticoagulation during expanded hemodialysis.

Efficacy and safety of expanded hemodialysis in hemodialysis patients: a meta-analysis and systematic review.

BACKGROUND: Expanded hemodialysis (HDx) is a new dialysis modality, but a systematic review of the clinical effects of using HDx is lacking. This systematic review and meta-analysis aimed to assess the efficacy and safety of HDx for hemodialysis (HD) patients. METHODS: PubMed, the Cochrane library, and EMBASE databases were systematically searched for prospective interventional studies comparing the efficacy and safety of HDx with those of high flux HD or HDF in HD patients. RESULTS: Eighteen trials including a total of 853 HD patients were enrolled. HDx increased the reduction ratio (RR) of ß2-microglobulin (SMD 6.28%, 95% CI 0.83, 1.73, p = .02), κFLC (SMD 15.86%, 95% CI 6.96, 24.76, p = .0005), and λFLC (SMD 22.42%, 95% CI, 17.95, 26.88, p < .0001) compared with high flux HD. The RR of ß2-microglobulin in the HDx group was lower than that in the HDF group (SMD -3.53%, 95% CI -1.16, -1.9, p < .0001). HDx increased the RRs of κFLC (SMD 1.34%, 95% CI 0.52, 2.16, p = .001) and λFLC (SMD 7.28%, 95% CI 1.08, 13.48, p = .02) compared to HDF. There was no significant difference in albumin loss into the dialysate between the HDx and HDF groups (SMD 0.35 g/session, 95% CI -2.38, 3.09, p = .8). CONCLUSIONS: This meta-analysis indicated that compared with high-flux HD and HDF, HDx can increase the clearance of medium and large-molecular-weight uremic toxins. And it does not increase the loss of albumin compared with HDF.

Updates on hemodialysis techniques with a common denominator: The personalization of the dialytic therapy.

Hemodialysis (HD) is a life-saving therapy for patients with end-stage renal disease. In dialyzed patients, the prevalence of multi-morbidity is rising driven by various factors, such as the population aging, the incomplete correction of uremia, and the side effects of the dialysis therapy itself. Each dialyzed patient has their own specific clinical and biochemical problems. It is therefore unthinkable that the same dialysis procedure can be able to meet the needs of every patient on chronic dialysis. We have very sophisticated dialysis machines and different dialysis techniques and procedures beyond conventional HD, such as hemodiafiltration (HDF) with pre- and post-dilution, acetate-free biofiltration (AFB), hemofiltration (HF), and expanded HD. Each of these techniques has its own specific characteristics. To solve some intradialytic clinical issues, such as arterial hypotension and arrhythmias, we have biofeedback systems with automatic regulation of the blood volume, body temperature, arterial pressure, as well as potassium profiling techniques in the dialysis bath. New technical innovations, such as citrate-containing dialysate or heparin-coated membranes, could reduce the risk of bleeding. To better address to patient needs, the strengths and weaknesses of each of these systems must be well-known, in order to have a personalized dialysis prescription for each patient.

Evaluation and comparison of polysulfone TS-UL and PMMA NF-U dialyzers versus expanded hemodialysis and postdilution hemodiafiltration.

Toray has created a new generation of dialyzers, the polysulphone (TS) UL series, and polymethylmethacrylate (PMMA) NF-U series, which offer enhanced efficacy over the previous TS-S series and NF-H series. The aim of this study was to evaluate the safety and efficacy of these dialyzer series versus contrasted expanded hemodialysis (HDx) and postdilution hemodiafiltration (HDF). We conducted a prospective study in 12 patients. Each patient underwent six dialysis sessions: FX80 Cordiax in HD, Toraysulfone TS-1.8 UL in HD, Theranova 400 in HDx, polymethylmethacrylate (PMMA) NF-2.1 U in HDF, Toraysulfone TS-2.1 UL in HDF, and FX80 Cordiax in HDF. The removal ratios (RRs) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. Dialysate albumin loss was also measured. The RRs for ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, and α1 -acid glycoprotein were higher with the TS-2.1 UL and FX80 Cordiax dialyzers in HDF than those obtained with HD treatments and NF-2.1 U in HDF. The ß2 -microglobulin, myoglobin, and prolactin RRs were also higher with HDx than those obtained with HD treatments. The myoglobin and prolactin RRs were higher with TS-1.8 UL in HD than those obtained with helixone dialyzers in HD. Dialysate albumin loss was less than 3 g in all situations except in TS-2.1 UL in HDF. The highest global removal score values were obtained with the TS-2.1 UL and helixone dialyzers in HDF. Significant differences were found between all study situations. In conclusion, the new generation dialyzers, Toraysulfone TS Series UL and PMMA NF-U series, show excellent behaviour and tolerance in HD and HDF, representing an upgrade versus their predecessor series. The higher permeability of the TS UL series has been proven with higher efficiency in HD and maximum performance in HDF. The new PMMA NF-U series allows the use of HDF with good efficiency and complete safety.

Efficacy and safety of the Clearum dialyzer.

The Clearum dialyzer, built by Medtronic, became commercially available in several European countries in 2020, but there are still no reports of in vivo data. The aim of this study was to evaluate the efficacy and risk of hypoalbuminemia of this dialyzer compared with previously evaluated hemodialysis (HD), expanded hemodialysis (HDx), and postdilution hemodiafiltration (HDF) treatments. A prospective study was carried out in 15 patients. Each patient underwent seven dialysis sessions: FX80 Cordiax in HD, Clearum HS17 in HD, Phylther 17-SD in HDx, Theranova 400 in HDx, Phylther 17-G in postdilution HDF, Clearum HS17 in postdilution HDF, and FX80 Cordiax in postdilution HDF. The reduction ratios of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. Dialysate albumin loss was also measured. Comparison of dialysis techniques revealed no differences between small molecules, but HDx and HDF were significantly higher than HD with medium and large molecular weights. The Clearum dialyzer in HDF obtained similar results to FX80 Cordiax in HDF, was slightly superior to Phylther 17-G in HDF, and was statistically superior to both dialyzers in HDx. Albumin losses with the Clearum dialyzer were among the lowest, both in HD and HDF treatments. The highest global removal score (GRS) values were obtained with the helixone and Clearum dialyzers in HDF, with similar results both in HD and HDF. In addition, the GRS values with HDx treatments were statistically significantly higher than those with HD. The new Clearum dialyzer has excellent behavior and tolerance in HD and HDF. Its adequate permeability has been proven with its maximal performance in HDF, which could represent an upgrade versus its predecessor polyphenylene dialyzers.

Frontiers in hemodialysis: Innovations and technological advances.

As increasing demand for hemodialysis (HD) treatment incurs significant financial burden to healthcare systems and ecological burden as well, novel therapeutic approaches as well as innovations and technological advances are being sought that could lead to the development of purification devices such as dialyzers with improved characteristics and wearable technology. Novel knowledge such as the development of more accurate kinetic models, the development of novel HD membranes with the use of nanotechnology, novel manufacturing processes, and the latest technology in the science of materials have enabled novel solutions already marketed or on the verge of becoming commercially available. This collaborative article reviews the latest advances in HD as they were presented by the authors in a recent symposium titled "Frontiers in Haemodialysis," held on 12th December 2019 at the Royal Society of Medicine in London.

Determining factors for hemodiafiltration to equal or exceed the performance of expanded hemodialysis.

The aim of the study was to compare expanded hemodialysis (HDx) with hemodiafiltration (HDF) at different infusion flows to identify the main determinants, namely blood flow (Qb), replacement volume, infusion flow (Qi), ultrafiltration flow (Quf ), filtration fraction (FF), and the point at which the effectiveness of HDF equals or exceeds that of HDx. We conducted a prospective, single-center study in 12 patients. Each patient underwent 12 dialysis sessions: six sessions with Qb 350 and six with Qb 400 mL/min; with each Qb, one session was with HDx and five sessions were with FX80 (one in HD, and four with Qi 50, 75, 90/100 mL/min or autosubstitution in postdilution HDF). The reduction ratios (RR) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually and the global removal score (GRS) was calculated. The mean replacement volume with Qb 350 mL/min was 13.77 ± 0.92 L with Qi 50 mL/min, 20.75 ± 1.17 L with Qi 75, 23.83 ± 1.92 L with Qi 90, and 27.51 ± 2.77 L with autosubstitution. Similar results were obtained with Qb 400 mL/min, and the results were only slightly higher with Qi 100 mL/min or in autosubstitution. The GRS was positively correlated with replacement volume with Qb 350 (R2  = 0.583) and with Qb 400 (R2  = 0.584); with Quf with Qb 350 (R2  = 0.556) and with Qb 400 (R2  = 0.604); and also with FF with Qb 350 (R2  = 0.556) and with Qb 400 mL/min (R2  = 0.603). The minimum convective volume in HDF from which it is possible to overcome the efficacy of HDx was 19.2 L with Qb 350 and 17.6 L with Qb 400 mL/min. The cut-off point of Quf at which HDF exceeded the effectiveness of HDx was 80.6 mL/min with Qb 350 and 74.1 mL/min with Qb 400 mL/min. The cut-off point at which FF in HDF exceeded the effectiveness of the HDx was 23.0% with Qb 350 and 18.6% with Qb 400 mL/min. In conclusion, this study confirms the superiority of postdilution HDF over HDx when replacement volume, convective volume, Quf , or FF exceeds certain values. Increasing the Qb in postdilution HDF manages to increase the convective dose and more easily overcome the HDx.

Is Expanded Hemodialysis an Option to Online Hemodiafiltration for Small- and Middle-Sized Molecules Clearance?

BACKGROUND: Recent evidence suggests a better reduction rate of some uremic toxins with expanded hemodialysis (HDx). METHODS: Prospective study including 8 hemodialysis patients. We divided the study in 2 phases; within the first one, we assigned 4 patients (group 1) to undergo online hemodiafiltration with a PF 210H dialyzer, and the other 4 patients (group 2) to undergo HDx with the high retention onset Theranova 500 dialyzer during 24 sessions. Later, during the second phase and after a washout period, the same patients were switched to receive HDx (group 1) and HDF (group 2). RESULTS: No differences were found in the Urea and ß2-microglobulin reduction ratio. However, in the case of myoglobin, the reduction ratio with HDF was 35 vs. 60% with HDx (p < 0.001). Similarly, in the case of prolactin, the reduction ratio with HDF was 45 and 61% with HDx (p < 0.001). CONCLUSIONS: We conclude that HDx is not inferior to online hemodiafiltration in the clearance of small and middle molecules and could be superior in the clearance of larger middle molecules.

Quantification of Internal Filtration in Hollow Fiber Hemodialyzers with Medium Cut-Off Membrane.

BACKGROUND: Inadequate removal of molecules between 5 and 50 KDa may cause long-term complication in chronic hemodialysis. Medium cut-off (MCO) is a new class of membranes with enhanced sieving properties and negligible albumin loss. MCO membrane makes it possible to perform expanded hemodialysis (HDx), a technique based on high internal filtration (IF).The present study is designed to quantify IF in 2 MCO dialyzers (Theranova 400 and 500, Baxter, Deerfield, USA) using a nuclear imaging technique previously validated. METHODS: Blood and dialysate compartment pressure drop along with transmembrane pressure; they were measured in a closed in vitro circuit with human blood (blood flow [QB] = 300 and 400 mL/min; dialysate flow 500 mL/min; net ultrafiltration rate 0 mL/min). A non-diffusible marker molecule (albumin macro-aggregates labeled with 99Tc metastable) was injected in the blood compartment and nuclear emission was recorded by a gamma camera. Relative variations in the concentration of the marker molecule along the length of the filter were used to calculate local cross filtration. RESULTS: Based on marker concentration profiles, IF was estimated. For Theranova 400, IF were 29.7 and 41.6 mL/min for QB of 300 and 400 mL/min. For Theranova 500, IF were 31.6 and 53.1 mL/min for QB of 300 and 400 mL/min respectively. CONCLUSIONS: MCO membrane provides significant amounts of IF due to the particular combination between hydraulic permeability of the membrane and reduced inner diameter of the fibers. High IF combined with enhanced sieving profile of MCO membrane leads to improved removal of a wider spectrum of uremia retention molecules in HDx, without requiring complex equipment.

Intradialytic Tolerance and Recovery Time in Different High-Efficiency Hemodialysis Modalities.

There are several forms of maintenance high-efficiency hemodialysis (HD), including hemodiafiltrations (HDF) in different technical modes and expanded HD, using dialyzers with medium cut-off membranes. The aim of the study was to assess the intradialytic tolerance and length of dialysis recovery time (DRT) in these modalities. This is an exploratory, crossover study in maintenance HD patients with low comorbidity and no clinical indications for the use of high-efficiency HD, who were exposed to five intermittent dialyses in random order: high-flux hemodialysis (S-HD), expanded HD (HDx), pre-dilution HDF (PRE-HDF), mix-dilution HDF (MIX-HDF) and post-dilution HDF (POST-HDF). Twenty-four dialysis sessions of each method were included in the analysis. Dialysis parameters, including blood flow rate, dialysis fluid flow rate and temperature, and pharmacological treatment were constant. Average total convection volume for post-HDF, pre-HDF and mix-HDF were 25.6 (3.8), 61.5 (7.2) and 47.1 (11.4) L, respectively. During all therapies, patients were monitored for the similarity of their hydration statuses using bioimpedance spectroscopy, and for similar variability over time in systemic blood pressure and cardiac output, while peripheral resistance was monitored using impedance cardiography. The lowest frequency of all intradialytic adverse events were observed during HDx. Delayed DRT was the shortest during PRE-HDF. Patients were also more likely to report immediate recovery while receiving PRE-HDF. These differences did not reach statistical significance; however, the study results suggest that intradialytic tolerance and DRT may depend on the dialysis method used. This supports the need of taking into account patient preferences and quality of life while individualizing high-efficiency therapy in HD patients.

Expanded Hemodialysis Enhancement in Middle Molecule Clearance for Patients With Low Blood Flow Rates of Tunneled Dialysis Catheters.

INTRODUCTION: Expanded hemodialysis (HDx), being based on medium cut-off (MCO) membranes, improves the removal of medium molecule uremic toxins. HDx efficacy has been proven with blood flow rates (Qb) of 350-400 ml/min, while low Qb have only been assessed in single sessions. We evaluated the effectiveness of HDx in patients with tunneled central venous catheters (CVCs) and low Qb over six months, comparing it with high-flux hemodialysis (HF-HD). METHODS: The study included 10 patients with a mean age of 79±12 years and mean Qb of 237 ± 12 ml/min. Reduction ratios (RRs) and predialysis serum levels were measured for ß2-microglobulin (B2M), free κ and λ light chains (FLC), prolactin (PRL), interleukin-6 (IL-6), albumin, and urea after HF-HD and at one, three, and six months of HDx. Erythropoiesis-stimulating agent (ESA) resistance index (ERI) was also evaluated. RESULTS: B2M, κ-FLC, λ-FLC, and PRL RRs were significantly higher with HDx. IL-6, albumin, and urea RRs did not show a statistical difference between the two treatments. Predialysis B2M concentrations were significantly lower after three and six months of HDx, matching up to increased B2M clearance (spKt/V). A decrease in albumin concentrations was observed, with median levels significantly reduced at months seven and eight (35.3 and 35.5 g/L, respectively) but recovering afterwards. ERI was significantly lower during HDx, reaching a 30% reduction at month six. CONCLUSIONS: HDx was feasible, safe, and superior to HF-HD in patients with low Qb rates of tunneled dialysis catheters. The present data expand options for HDx prescription, with particular regard for patients who cannot achieve high convective volumes due to inadequate vascular access.

Trial design of the MOTheR HDx study: a multicenter, open-label, prospective, randomized study to explore the morbidity and mortality in patients dialyzed with the Theranova HDx in comparison with online hemodiafiltration.

Background: Dialysis patients have been maintaining a high rate of cardiovascular morbidity and mortality. For this reason, it is to introduce necessary new technical advances in clinical practice. There is a relation between toxins retention and inflammation, mortality and morbidity. Medium cut-off (MCO) membranes are a new generation of membranes that allow the removal of a greater number of medium-sized molecules compared with high-flux hemodialysis (HF-HD), but retaining albumin. MCO membranes have an increased permeability and the presence of internal filtration. Because of these special properties, MCO generated a new concept of therapy called expanded HD (HDx). Until now, online hemodiafiltration (OL-HDF) has demonstrated its superiority, in terms of survival, compared with HF-HD. However, the comparison between OL-HDF and HDx remains an unsolved question. Methods: The MOTheR HDx study trial (NCT03714386) is an open-label, multicenter, prospective, 1:1 randomized, parallel-group trial designed to evaluate the efficacy and safety of HDx compared with OL-HDF in patients treated for dialysis in Spain for up to 36 months. The main endpoint is to determinate whether HDx is non inferior to OL-HDF at reducing the combined outcome of all-cause death and stroke (ischemic or hemorrhagic), acute coronary syndrome (angina and myocardial infarction), peripheral arterial disease (amputation or revascularization) and ischemic colitis (mesenteric thrombosis). Results: The trial has already started.

Expanded Hemodialysis ameliorates uremia-induced impairment of vasculoprotective KLF2 and concomitant proinflammatory priming of endothelial cells through an ERK/AP1/cFOS-dependent mechanism.

Aims: Expanded hemodialysis (HDx) therapy with improved molecular cut-off dialyzers exerts beneficial effects on lowering uremia-associated chronic systemic microinflammation, a driver of endothelial dysfunction and cardiovascular disease (CVD) in hemodialysis (HD) patients with end-stage renal disease (ESRD). However, studies on the underlying molecular mechanisms are still at an early stage. Here, we identify the (endothelial) transcription factor Krüppel-like factor 2 (KLF2) and its associated molecular signalling pathways as key targets and regulators of uremia-induced endothelial micro-inflammation in the HD/ESRD setting, which is crucial for vascular homeostasis and controlling detrimental vascular inflammation. Methods and results: First, we found that human microvascular endothelial cells (HMECs) and other typical endothelial and kidney model cell lines (e.g. HUVECs, HREC, and HEK) exposed to uremic serum from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation II (PERCI-II) crossover clinical trial - comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes - exhibited strongly reduced expression of vasculoprotective KLF2 with HF dialyzers, while dialysis with MCO dialyzers led to the maintenance and restoration of physiological KLF2 levels in HMECs. Mechanistic follow-up revealed that the strong downmodulation of KLF2 in HMECs exposed to uremic serum was mediated by a dominant engagement of detrimental ERK instead of beneficial AKT signalling, with subsequent AP1-/c-FOS binding in the KLF2 promoter region, followed by the detrimental triggering of pleiotropic inflammatory mediators, while the introduction of a KLF2 overexpression plasmid could restore physiological KLF2 levels and downmodulate the detrimental vascular inflammation in a mechanistic rescue approach. Conclusion: Uremia downmodulates vasculoprotective KLF2 in endothelium, leading to detrimental vascular inflammation, while MCO dialysis with the novel improved HDx therapy approach can maintain physiological levels of vasculoprotective KLF2.

Clinical Safety of Expanded Hemodialysis Compared with Hemodialysis Using High-Flux Dialyzer during a Three-Year Cohort.

Expanded hemodialysis (HD) equipped with a medium cut-off (MCO) membrane provides superior removal of larger middle molecules. However, there is still little research on the long-term benefits of expanded HD. Over a three-year period, this observational study evaluated the efficacy and safety profile of expanded HD for inflammatory cytokines, including IL-6. We conducted a prospective cohort study to investigate the inflammatory cytokine changes and a retrospective observational cohort study to investigate long-term clinical efficacy and safety over a three-year period. We categorized the patients according to dialyzer used: MCO and high-flux (HF) dialyzer. The inflammatory cytokines, including IFN-γ, IL-1ß, IL-6, and TNF-α, were measured annually. The concentrations and changes of the four cytokines over time did not differ between the HF group (n = 15) and MCO group (n = 27). In both prospective and retrospective (HF group, n = 38; MCO group, n = 76) cohorts, there were no significant differences in either death, cardiovascular events, infections, or hospitalizations. Furthermore, the temporal changes in laboratory values, including serum albumin and erythropoietin prescriptions, did not differ significantly between the two groups in either the prospective or retrospective cohorts. In conclusion, clinical efficacy and safety outcomes, as well as inflammatory cytokines, did not differ with expanded HD compared with HF dialysis during a three-year treatment course, although the level of inflammatory cytokine was stable.

Comparison of four medium cut-off dialyzers.

Background: 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). Methods: 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, ß2-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. Results: The differences in efficacy between the evaluated dialyzers were minimal in small molecules and even up to the size of ß2-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. Conclusions: 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.