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Background: Patients with end-stage kidney disease (ESKD) have altered immunity. Patients on hemodialysis (HD) present a coexistence of immunodeficiency and activation of the immune system. We evaluated the immunophenotypic profile induced by the medium cut-off of Theranova filter during a single HD session in the same individual. Methods: This pilot observational study explored 11 patients (75 ± 8 years and 73% male). Blood samples were collected prior to (predialytic, PRE) and after 4 h (postdialytic, POST) standard HD session with a medium cut-off, polyarylethersulfone and polyvinylpyrrolidone blend, BPA-free membrane. We performed an immunophenotyping characterization by using flow cytometry. We evaluated eryptosis RBCs and HLA-DR expression on monocytes and Treg cells. Results: The percentages of eryptosis in lymphocytes (CD3+), lymphocyte T helper (CD3+ and CD4+) cells, and monocytes (CD45+ and CD14+) were similar pre- and post-HD. On the contrary, HLA-DR expression and Treg cell numbers significantly decreased after HD. Conclusions: Many studies have focused on the comparison between healthy volunteers and HD patients, but very few have focused on the changes that occur after an HD session in the same individual. With this pilot observational study, we have revealed an immunomodulation driven by HD treatment with Theranova filter. Our preliminary results can be considered to be a hypothesis, generating and stimulating further studies with better designs and larger populations.

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BACKGROUND: Middle uremic toxins (MUTs) can cause anemia and erythropoietin hyporesponsiveness. Theranova dialyzers may improve anemia management by removing MUTs. Hence, the impact of Theranova dialyzers on erythropoietin responsiveness was studied. METHODS: This exploratory single-center prospective observational study, encompassing 50 patients undergoing dialysis with either the Theranova-400 or FX80 membrane for 6 months, involved monthly tracking of hemoglobin levels, weight-adjusted erythropoiesis-stimulating agent (w-ESA) dosing, and erythropoietin resistance index (ERI), with ESA treatment decisions guided by a proprietary algorithm. RESULTS: The groups were similar in terms of demographics and baseline laboratory test results. The median hemoglobin levels, w-ESA and ERI, were found to be similar between FX80 and Theranova-400 groups at both baseline (11.06 vs 10.57, p = 0.808; 92.3 vs 105.2, p = 0.838; 8.1 vs 10.48, p = 0.876) and the end of the study (11.43 vs 11.03, p = 0.076; 48.7 vs 71.5; 4.48 vs 6.41, p = 0.310), respectively. There was a trend toward lower w-ESA and ERI at the end of the study compared to baseline in both groups, but the difference was non-significant. CONCLUSIONS: Based on this study of 50 patients undergoing high-flux dialysis with near-target hemoglobin levels, switching to Theranova 400 dialyzers compared to FX80 dialyzers did not show statistically significant differences in maintaining hemoglobin levels, reducing ESA dose, or lowering ERI. The non-randomized design and small sample size limit the study's power to detect true differences. Larger, randomized trials are needed to confirm findings and definitively assess Theranova 400's benefits.

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INTRODUCTION: Medium cut-off (MCO) membranes may be able to remove middle-large uremic toxins that are retained in the body, which has been linked to various risk factors including malnutrition-inflammation score (MIS). The effect of MCO dialyzers on MIS has been studied. METHODS: This single-center exploratory prospective observational study enrolled maintenance hemodialysis patients who underwent dialysis using either MCO (Theranova 400) or high-flux (FX80) membranes as part of their regular care. Measurements of MIS, body weight, height, body mass index, and various biochemical markers were taken at the beginning and conclusion of the study. RESULTS: This study included 50 patients who were treated with either the Theranova 400 (n = 25) or the FX80 (n = 25) for a period of 6 months. The two groups were similar in terms of demographics, duration of hemodialysis treatment, and baseline biochemical test results. Theranova 400 had no significant impact on the median MIS (6 [6-10] vs. 7 [5-10], p 0.575) and serum albumin levels (4.07 [3.92-4.22] vs. 4.04 [3.85-4.30], p 0.689), while the FX80 resulted in a significant increase in MIS (6 [5-8] vs. 8 [6-10], p 0.033) and a significant decrease in serum albumin levels (4.23 [4.03-4.36] vs. 3.98 [3.77-4.12], p 0.027) at the end of the study. DISCUSSION/CONCLUSION: After 6 months of treatment, the MCO dialyzer did not demonstrate a statistically significant difference in the MIS when compared to the high-flux dialyzer. However, MIS worsening was significantly less in the MCO group, indicating the potential benefits of MCO membranes in maintaining nutritional status. Further research is required to validate these results.

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Introduction: The interaction between blood and dialysis membrane increases the risk of clot formation. Membrane properties can interfere with coagulation activation during dialysis. Heparin is usually used to ensure anticoagulation, which can be monitored by the Activated Clotting Time (ACT) test. The purpose of this study was to compare the ACT of patients with chronic kidney disease (CKD) undergoing hemodialysis with high-flux (HF) and medium cut-off (MCO) membranes. Methods: This is a prospective, randomized, crossover study in which 32 CKD patients were dialyzed for 12 weeks with each membrane. Blood clotting measured by ACT was evaluated at the beginning, 2nd, and 4th hour of the dialysis session. Throughout the study, there were no changes in the dose or administration method of heparin. Results: Patients mainly were middle-aged, non-black males on hemodialysis for eight years. Before randomization, ACT values were 132 ± 56, 195 ± 60, and 128 ± 32 seconds at pre-heparinization, 2nd and 4th hour, respectively. After 12 weeks, ACT values in HF and MCO groups were 129 ± 17, 205 ± 65 and 139 ± 38 seconds, and 143 ± 54, 219 ± 68 and 142 ± 45 seconds, respectively. An ANOVA model adjusted and unadjusted for repeated measures showed a significant time but no treatment or interaction effects. In an additional paired-sample analysis, no difference between ACT values of HF and MCO Groups was observed. Discussion and Conclusion: There was no difference regarding the ACT test during dialysis therapy using HF or MCO membranes. This data suggests that no adjustment in the dose or administration method of heparin is necessary with the use of MCO dialysis membranes.

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INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused extensive morbidity and mortality worldwide. Hemodialysis (HD) patients are both vulnerable to COVID-19 infection and tend to suffer greater disease severity and mortality. This retrospective study aimed to compare medium cut-off (MCO) and low-flux (LF) membrane dialyzers in terms of interleukin-6 (IL-6) reduction, change in inflammatory state, intradialytic complications, and mortality in chronic HD patients with COVID-19. METHOD: HD patients with a confirmed COVID-19 infection were admitted to the hospital for 10-14 days and underwent HD at the COVID-HD unit. Choice of dialyzer membrane used (MCO vs. LF) depended on the primary nephrologist(s). We collected data on demographics, baseline characteristics, laboratory results, diagnosis, treatments, HD prescription, hemodynamic status during HD, and mortality at 14 and 28 days after. RESULTS: IL-6 reduction ratio (RR) in the MCO group was 9.7 (interquartile range, 71.1) percent, which was significantly higher than that of the LF group (RR, -45.7 [interquartile range, 70.2] percent). The incidence rate of intradialytic hypotension in the MCO group was 3.846 events per 100 dialysis hours (95% confidence interval [CI], 1.954-6.856), which was significantly lower than that of the LF group (9.057; 95% CI, 5.592-13.170). Overall, mortality was not significantly different between the two groups. CONCLUSION: The MCO membrane was more effective in removing IL-6 and was better tolerated than the LF membrane. Large, randomized controlled trials are required to confirm the relative benefits of the MCO membrane, especially mortality. However, due to the COVID-19 pandemic, our results suggest that the MCO membrane may be beneficial in chronic HD patients with COVID-19.

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BACKGROUND: Medium cut-off (MCO) membranes enhance large middle-molecule clearance while selectively retaining molecules >45 000 Da. OBJECTIVES: We undertook a systematic review and meta-analysis comparing the effects of MCO versus high-flux membranes on biomarkers. METHODS: We searched MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science from January 2015 to July 2020, and gray literature sources from 2017. We included randomized (RS) and nonrandomized studies (NRS) comparing MCO and high-flux membranes in adults (>18 years) receiving maintenance hemodialysis. We performed study selection, data extraction, and quality appraisals in duplicate and used the Grading of Recommendations Assessment, Development, and Evaluation framework. Outcomes included solute removal (plasma clearance or dialysate quantitation), reduction ratios, and predialysis serum concentrations for a range of prespecified large middle molecules. RESULTS: We identified 26 eligible studies (10 RS and 16 NRS; N = 1883 patients; patient-years = 1366.3). The mean difference (MD) for albumin removal was 2.31 g per session (95% confidence interval [CI], 2.79 to 1.83; high certainty), with a reduction in predialysis albumin of -0.12 g/dl (95% CI, -0.16 to -0.07; I 2 = 0%; high certainty) in the first 24 weeks, returning to normal (MD = -0.02 g/dl, 95% CI, -0.07 to -0.03; I 2 = 56%; high certainty) after 24 weeks. We also found with high certainty that MCO dialysis resulted in a large increase (standardized mean difference [SMD]> 2.0 for all) in ß2-microglobulin, κ- and λ-free light chains, and myoglobin removal, resulting in moderate (SMD > 0.5) to large (SMD > 0.8) reductions in predialysis concentrations for all of these solutes. Medium cut-off dialysis increased the reduction ratio for tumor necrosis factor-alpha (TNF-α) by 7.7% (95% CI, 4.7 to 10.6; moderate certainty), and reduced predialysis TNF-α by SMD -0.48 (95% CI, -0.91 to -0.04; moderate certainty). We found with moderate certainty that MCO dialysis had little to no effect on predialysis interleukin-6 (IL-6) plasma concentrations. Medium cut-off dialysis reduced mRNA expression of TNF-α and IL-6 in peripheral leukocytes by MD -15% (95% CI, -19.6 to -10.4; moderate certainty) and -8.8% (95% CI, -10.2 to -7.4; moderate certainty), respectively. CONCLUSION: Medium cut-off dialysis increases the clearance of a wide range of large middle molecules and likely reduces inflammatory mediators with a concomitant transient reduction in serum albumin concentration. The net effect of MCO dialysis on large middle molecules could translate into important clinical effects.

CONTEXTE: Les membranes MCO (Medium cut-off) améliorent la clairance des moyennes molécules de masse moléculaire élevée tout en retenant sélectivement les molécules de plus de 45 000 Da. OBJECTIFS: Nous avons entrepris une revue systématique et une méta-analyse comparant les effets des membranes MCO et des membranes à perméabilité élevée sur certains biomarqueurs. MÉTHODOLOGIE: Nous avons effectué des recherches dans MEDLINE, EMBASE, CINAHL, Cochrane Library et Web of Science entre janvier 2015 et juillet 2020, et dans des sources de littérature grise de 2017. Nous avons inclus les études randomisées (ÉR) et non randomisées (ÉNR) comparant les membranes MCO et les membranes à perméabilité élevée chez les adultes recevant une hémodialyse d'entretien. Nous avons procédé à la sélection des études, à l'extraction des données et à l'évaluation de la qualité en duplicata, puis nous avons utilisé la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation). Les résultats comprenaient l'élimination du soluté (clairance plasmatique ou quantification du dialysat), les rapports de réduction et les concentrations sériques prédialyse pour une gamme de moyennes molécules à masse moléculaire élevée prédéterminées. RÉSULTATS: Nous avons répertorié 26 études admissibles (10 ÉR, 16 ÉNR; n = 1 883 patients; 1 366,3 années-patients). La différence moyenne (DM) pour l'élimination de l'albumine était de 2,31 g par séance (IC 95 % : 2,79 à 1,83; haute certitude), avec une réduction de l'albumine prédialyse de -0,12 g/dl (IC 95 % : -0,16 à -0,07; I 2 = 0 %; haute certitude) au cours des 24 premières semaines, et un retour à la normale (DM = -0,02 g/dl; IC 95 % : -0,07 à -0,03; I 2 = 56 %; haute certitude) après 24 semaines. Nous avons constaté, avec une grande certitude, que la dialyse MCO entraînait une élimination importante de ß2-microglobuline, chaînes légères κ- et λ- et de myoglobine (différence moyenne standardisée [DMS] > 2,0 pour toutes), ce qui s'est traduit par des réductions modérées (DMS > 0,5) à importantes (DMS > 0,8) des concentrations prédialyse pour tous ces solutés. La dialyse MCO a haussé le taux de réduction du TNF-α de 7,7 % (IC 95 % : 4,7 à 10,6; certitude modérée) et réduit le TNF-α prédialyse (DMS = -0,48; IC 95 % : -0,91 à -0,04; certitude modérée). Nous avons constaté, avec une certitude modérée, que la dialyse MCO n'a que peu ou pas d'effet sur les concentrations plasmatiques d'IL-6 prédialyse. La dialyse MCO a réduit l'expression de l'ARNm du TNF-α et d'IL-6 dans les leucocytes périphériques avec une DM de -15 % (IC 95 % : -19,6 à -10,4; certitude modérée) et de -8,8 % (IC 95 % : -10,2 à -7,4; certitude modérée) respectivement. CONCLUSION: La dialyse MCO augmente la clairance d'une vaste gamme de moyennes molécules de haute masse moléculaire et semble réduire les médiateurs inflammatoires avec une réduction transitoire concomitante de la concentration en albumine sérique. L'effet net de la dialyse MCO sur les moyennes molécules de haute masse moléculaire pourrait se traduire par des effets cliniques importants.

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BACKGROUND: A novel medium cut-off (MCO) dialyzer (Theranova, Baxter Healthcare, Deerfield, IL, USA) enhances large middle molecule clearance while retaining selectivity for molecules >45 000 Da. OBJECTIVE: We undertook a systematic review and meta-analysis evaluating clinical outcomes with MCO vs high-flux membranes. METHODS: We searched MEDLINE, EMBASE, CINAHL, Cochrane Library, and Web of Science through July 2020, and gray literature sources from 2017. We included randomized (RS) and nonrandomized studies (NRS) comparing MCO and high-flux membranes in adults receiving maintenance hemodialysis. Pairs of reviewers performed study selection, data extraction, and risk of bias assessment in duplicate. We conducted random-effects pairwise meta-analyses to pool results across studies and used the Grading of Recommendations Assessment, Development and Evaluation approach to assess evidence certainty. RESULTS: We identified 22 eligible studies (6 RS, 16 NRS; N = 1811 patients; patient-years = 1546). The MCO dialyzer improved (estimate; 95% confidence interval [CI]; certainty rating) quality of life (mean difference [MD] = 16.7/100 points; 6.9 to 26.4; moderate), Kidney Disease Quality of Life Instrument (KDQOL) subscales-burden (MD = 4.0; 1.1 to 6.9; moderate) and effects (MD = 5.4; 3.2 to 7.6; moderate), pruritus (MD = -4.4; -7.1 to -1.7; moderate), recovery time (MD = -420 minutes; -541 to -299; high), and restless legs syndrome (odds ratio = 0.39; 0.29 to 0.53; moderate). There was little to no difference in all-cause mortality (risk difference = -0.4%; -2.8 to 2.1; moderate) and serious adverse events (rate ratio = 0.63; 0.38 to 1.04; low). MCO dialysis reduced hospitalization (rate ratio = 0.48; 0.27 to 0.84; low), infection (rate ratio = 0.38; 0.17 to 0.85; moderate), hospitalization days (MD = -1.5 days; 95% CI, -2.22 to -0.78; moderate), erythropoiesis resistance index (MD = -2.92 U/kg/week/g/L; 95% CI, -4.25 to -1.6; moderate) and cumulative iron use over 12 weeks (MD = -293 mg; 95% CI, -368 to -218; moderate). We found with low certainty that MCO dialysis had little to no effect on KDQOL symptoms/problem list, pain, and physical health and moderate certainty that MCO dialysis likely has no effect on the KDQOL mental health composite. CONCLUSIONS: We found with predominantly moderate certainty that the MCO dialyzer improves several patient-important outcomes with no apparent risks or harms. More definitive studies are needed to better quantify the effects of MCO membranes on mortality, hospitalization, and other rare events.

CONTEXTE: Un nouveau dialyseur MCO (Medium cut-off) (Theranova, Baxter Healthcare, Deerfield, IL, É.-U.) améliore la clairance des molécules importantes de taille moyenne tout en maintenant la sélectivité des molécules de plus de 45 000 Da. OBJECTIFS: Nous avons entrepris une revue systématique et une méta-analyse évaluant les résultats cliniques des membranes MCO par rapport aux membranes à perméabilité élevée. MÉTHODOLOGIE: Nous avons effectué des recherches dans MEDLINE, embase, CINAHL, Cochrane Library et Web of Science jusqu'en juillet 2020, et dans des sources de littérature grise de 2017. Nous avons inclus les études randomisées (ÉR) et non randomisées (ÉNR) comparant les membranes MCO et les membranes à perméabilité élevée chez les adultes recevant une hémodialyse d'entretien. Des paires de réviseurs ont procédé à la sélection des études, à l'extraction des données et à l'évaluation du risque de biais en duplicata. Nous avons effectué des méta-analyses à effets aléatoires par paires pour regrouper les résultats des différentes études, puis nous avons employé la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation) pour évaluer la certitude des preuves. RÉSULTATS: Nous avons répertorié 22 études admissibles (6 ÉR, 16 ÉNR ; n=1811 patients; 1 546 années-patients). Le dialyseur MCO a amélioré (estimation; IC à 95 %; évaluation de la certitude) la qualité de vie (différence moyenne [DM] = 16,7/100 points; 6,9 à 26,4; modérée), les sous-échelles KDQOL ­ le fardeau de la maladie (DM = 4,0; 1,1 à 6,9; modérée), les effets (DM = 5,4; 3,2 à 7,6; modérée), le prurit (DM = -4,4; -7,1 à -1,7; modérée), le temps de récupération (DM = -420 minutes; -541 à -299; élevée) et le syndrome des jambes sans repos (rapport de cotes = 0,39; 0,29 à 0,53; modéré). On a noté peu ou pas de différence pour la mortalité toutes causes confondues (risque différentiel = -0,4 %; -2,8 à 2,1; modérée) et les événements indésirables graves (rapport des taux = 0,63; 0,38 à 1,04; faible). La dialyse par MCO a réduit les hospitalisations (rapport des taux = 0,48; 0,27 à 0,84; faible), les infections (rapport des taux = 0,38; 0,17 à 0,85; modérée), la durée des hospitalisations (DM = -1,5 jour; -2,22 à -0,78; modérée), l'indice de résistance à l'érythropoïèse (DM = -2,92 U/kg/semaine/g/L; -4,25 à -1,6; modérée) et l'utilisation cumulative de fer sur 12 semaines (DM = -293 mg; -368 à -218; modérée). Nous avons constaté, avec peu de certitude, que la dialyse MCO n'avait que peu ou pas d'effet sur les symptômes/problèmes liés à la KDQOL, de même que sur la douleur et la santé physique. Et nous avons constaté, avec une certitude modérée, que la dialyse MCO n'avait probablement aucun effet sur le composite de santé mentale de la KDQOL. CONCLUSION: Nous avons constaté avec une certitude principalement modérée que le dialyseur MCO améliorait plusieurs résultats importants pour le patient sans risques ou préjudices apparents. Des études plus définitives sont nécessaires afin de mieux quantifier les effets des membranes MCO sur le taux de mortalité, les hospitalisations et les autres événements rares.

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Medium cut-off membrane (MCO) dialysers have been shown to remove a range of middle molecules, which are associated with adverse outcomes in haemodialysis (HD) patients, more effectively than high-flux HD. Vancomycin is widely used in HD patients for treating a variety of infections. To avoid subtherapeutic trough concentrations, it is important to understand vancomycin clearance in patients undergoing HD with the MCO membrane. This open label single centre, cross-over clinical study compared the vancomycin pharmacokinetics in chronic HD patients using MCO membrane (Theranova) and high-flux membrane (Revaclear). Five patients established on chronic HD who were due to receive vancomycin were enrolled. The study used alternating Theranova and Revaclear dialysis membranes over six consecutive sessions. Vancomycin was administered over the last one to two hours of each HD session. The maintenance dose was adjusted based on pre-HD serum concentrations. Over the 210 study samples, vancomycin clearance was higher with MCO-HD compared to high-flux HD but not statistically significant. Median percentage of vancomycin removal at 120 min by MCO membrane was 39% (20.6-51.5%) compared with 34.1% (21.3-48.4%) with high-flux HD. MCO-HD removes a slightly higher percentage of vancomycin at 120 min into dialysis compared to high-flux membrane dialysis in HD patients with infections. Application of vancomycin during the last one to two hours of each dialysis is required to maintain therapeutic concentrations to minimise loss through the dialyser and maintain therapeutic levels.

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