Performance of hemodialysis with novel medium cut-off dialyzers.
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ABSTRACT: Background
Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules.Methods
In two prospective, open-label, controlled, randomized, crossover pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF). Primary outcome was lambda free light chain (λFLC) overall clearance. Secondary outcomes included overall clearances and pre-to-post-reduction ratios of middle and small molecules, and safety of MCO HD treatments.Results
MCO HD provided greater λFLC overall clearance [least square mean (standard error)] as follows: study 1: MCO AA 8.5 (0.54), MCO BB 11.3 (0.51), MCO CC 15.0 (0.53) versus high-flux HD 3.6 (0.51) mL/min; study 2: MCO AA 10.0 (0.58), MCO BB 12.5 (0.57) versus high-flux HD 4.4 (0.57) and HDF 6.2 (0.58) mL/min. Differences between MCO and high-flux dialyzers were consistently significant in mixed model analysis (each P < 0.001). Reduction ratios of λFLC were greater for MCO. Clearances of α1-microglobulin, complement factor D, kappa FLC (κFLC) and myoglobin were generally greater with MCO than with high-flux HD and similar to or greater than clearances with HDF. Albumin loss was moderate with MCO, but greater than with high-flux HD and HDF.Conclusions
MCO HD removes a wide range of middle molecules more effectively than high-flux HD and even exceeds the performance of high-volume HDF for large solutes, particularly λFLC.
SUBMITTER: Kirsch AH
PROVIDER: S-EPMC5837492 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecently, 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).MethodsA 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.ResultsThe 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.ConclusionsThe 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.
| S-EPMC9664569 | biostudies-literature
Project description:Medium cut-off (MCO) dialyzers help remove larger middle molecules associated with symptoms related to the accumulation of uremic retention solutes. We investigated the effect of an MCO dialyzer on the improvement of quality of life (QOL) in maintenance hemodialysis (HD) patients. Forty-nine HD patients with high-flux dialysis were randomly assigned to either an MCO (Theranova 400, Baxter) or a high-flux (FX CorDiax 80 or 60, Fresenius Medical Care) dialyzer and completed the study. QOL was assessed at baseline and after 12 weeks of treatment using the Kidney Disease Quality of Life Short Form-36, and pruritus was assessed using a questionnaire and visual analog scale. The reduction ratios of middle molecules were also evaluated. Laboratory markers, including serum albumin, did not differ between the two groups after 12 weeks. Removals of kappa and lambda free light chains were greater for MCO dialyzer than high-flux dialyzer. The MCO group had higher scores than the high-flux group in the domains of physical functioning and physical role (75.2?±?20.8 vs. 59.8?±?30.1, P?=?0.042; 61.5?±?37.6 vs. 39.0?±?39.6, P?=?0.047, respectively), and the MCO group had lower mean scores for morning pruritus distribution and the frequency of scratching during sleep (1.29?±?0.46 vs. 1.64?±?0.64, P?=?0.034; 0.25?±?0.53 vs. 1.00?±?1.47, P?=?0.023, respectively). MCO dialyzers may improve patient-reported outcomes, particularly the physical components of QOL and uremic pruritus, in patients with high-flux dialyzers.
| S-EPMC7210312 | biostudies-literature
Project description:In this single-center prospective study of 20 patients receiving maintenance hemodialysis (HD), we compared the therapeutic effects of medium cut-off (MCO) and high flux (HF) dialyzers using metabolomics and proteomics. A consecutive dialyzer membrane was used for 15-week study periods: 1st HF dialyzer, MCO dialyzer, 2nd HF dialyzer, for 5 weeks respectively. 1H-nuclear magnetic resonance was used to identify the metabolites and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify proteins. To compare the effects of the HF and MCO dialyzers, orthogonal projection to latent structure discriminant analysis (OPLS-DA) was performed. OPLS-DA showed that metabolite characteristics could be significantly classified by 1st HF and MCO dialyzers. The Pre-HD metabolites with variable importance in projection scores ≥ 1.0 in both 1st HF versus MCO and MCO versus 2nd HF were succinate, glutamate, and histidine. The pre-HD levels of succinate and histidine were significantly lower, while those of glutamate were significantly higher in MCO period than in the HF period. OPLS-DA of the proteome also substantially separated 1st HF and MCO periods. Plasma pre-HD levels of fibronectin 1 were significantly higher, and those of complement component 4B and retinol-binding protein 4 were significantly lower in MCO than in the 1st HF period. Interestingly, as per Ingenuity Pathway Analysis, an increase in epithelial cell proliferation and a decrease in endothelial cell apoptosis occurred during the MCO period. Overall, our results suggest that the use of MCO dialyzers results in characteristic metabolomics and proteomics profiles during HD compared with HF dialyzers, which might be related to oxidative stress, insulin resistance, complement-coagulation axis, inflammation, and nutrition.
| S-EPMC8405670 | biostudies-literature
Project description:Few data are available regarding the association of dialyzer type with prognosis. In Japan, dialyzers are classified as types I, II, III, IV, and V based on β2-microglobulin clearance rates of < 10, < 30, < 50, < 70, and ≥ 70 mL/min, respectively. We investigated the relationship of the 5 dialyzer types with 1-year mortality. This nationwide cohort study used data collected at the end of 2008 and 2009 by the Japanese Society for Dialysis Therapy Renal Data Registry. We enrolled 203,008 patients on maintenance hemodialysis who underwent hemodialysis for at least 1 year and were managed with any of the 5 dialyzer types. To evaluate the association of dialyzer type with 1-year all-cause mortality, Cox proportional hazards models and propensity score-matched analyses were performed. After adjustment of the data with clinicodemographic factors, the type I, II, and III groups showed significantly higher hazard ratios (HRs) than the type IV dialyzers (reference). After adjustment for Kt/V and β2-microglobulin levels, the HRs were significantly higher in the type I and II groups. After further adjustment for nutrition- and inflammation-related factors, the HRs were not significantly different between the type IV and type I and II groups. However, type V dialyzers consistently showed a significantly lower HR. With propensity score matching, the HR for the type V dialyzer group was significantly lower than that for the type IV dialyzer group. Additional long-term trials are required to determine whether type V dialyzers, which are high-performance dialyzers, can improve prognosis.
| S-EPMC8192518 | biostudies-literature
Project description:The use of medium cut-off (MCO) polyarylethersulfone and polyvinylpyrrolidone blend membrane is an emerging mode in hemodialysis. Recent studies have shown that MCO membranes exhibit a middle high molecular weight uremic toxin clearance superior to standard high flux hemodialysis. We conducted a systematic literature review and meta-analysis of randomized controlled trials to investigate whether MCO membranes efficiently increase the reduction ratio of middle molecules, and to explore the potential clinical applications of MCO membranes. We selected articles that compared beta 2-microglobulin (β2M), kappa free light chain (κFLC), lambda free light chain (λFLC), interleukin-6 (IL-6), and albumin levels among patients undergoing hemodialysis. Five randomized studies with 328 patients were included. The meta-analysis demonstrated a significantly higher reduction ratio of serum β2M (p < 0.0001), κFLC (p < 0.0001), and λFLC (p = 0.02) in the MCO group. No significant difference was found in serum IL-6 levels after hemodialysis. Albumin loss was observed in the MCO group (p = 0.04). In conclusion, this meta-analysis study demonstrated the MCO membranes' superior ability to clear β2M, κFLC, and λFLC. Serum albumin loss is an issue and should be monitored. Further studies are expected to identify whether MCO membranes could significantly improve clinical outcomes and overall survival.
| S-EPMC9144787 | biostudies-literature
Project description:BACKGROUND:Inflammaging is a persistent, low-grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination. Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation. METHODS:We conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low-flux bicarbonate hemodialysis, 2) Low-flux bicarbonate hemodialysis with vitamin E?-?loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period. RESULTS:Hemodialysis kynurenine and kynurenine/L?-?tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low-flux bicarbonate hemodialysis with vitamin E?-?loaded dialyzers period, L?-?tryptophan serum levels remained unchanged vs both low-flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L?-?tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low-flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low-flux bicarbonate hemodialysis with vitamin E?-?loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60?min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line. CONCLUSIONS:The treatment with more biocompatible hemodialysis procedure as low-flux bicarbonate hemodialysis with vitamin E?-?loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low-flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low-flux bicarbonate hemodialysis with vitamin E?-?loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level. TRIAL REGISTRATION:NCT Number: NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.
| S-EPMC6858730 | biostudies-literature
Project description:This study compared the therapeutic effects of medium cut-off (MCO) and high flux (HF) dialyzers using metabolomics and proteomics. This was a single-center prospective trial of 20 patients receiving maintenance hemodialysis (HD). A consecutive dialyzer membrane was used for 15-week study periods as follows: 1st HF dialyzer, MCO dialyzer, 2nd HF dialyzer, for 5 weeks respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to identify proteins.
2021-11-03 | PXD026907 | Pride
Project description:BackgroundA 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.ObjectiveWe undertook a systematic review and meta-analysis evaluating clinical outcomes with MCO vs high-flux membranes.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.
| S-EPMC8785433 | biostudies-literature
Project description:BackgroundMedium cut-off (MCO) membranes enhance large middle-molecule clearance while selectively retaining molecules >45 000 Da.ObjectivesWe undertook a systematic review and meta-analysis comparing the effects of MCO versus high-flux membranes on biomarkers.MethodsWe 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.ResultsWe 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 β2-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.ConclusionMedium 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.
| S-EPMC8777328 | biostudies-literature
Project description:Rationale & objectiveCurrent hemodialysis (HD) treatments have limited ability to clear larger-molecular-weight uremic toxins. Retention is associated with increased symptom burden, low health-related quality of life (HRQoL), and high mortality. Improved clearance, using novel medium cut-off dialyzers, termed expanded HD (HDx), may be associated with improved subjective experience. We have previously developed a dynamic patient-reported outcome measure (PROM) instrument to allow iterative recording to better appreciate the overall burden of disease and assess the impact of therapy changes.Study designSingle-center interventional pilot study.Setting & participants28 patients established on maintenance HD, London, Ontario, Canada.InterventionInitial study consisting of 2-week observation (baseline-conventional high-flux HD) followed by 12 weeks of HDx. HRQoL was assessed using the dynamic PROM instrument thrice weekly (enabled in a dedicated app as the London Evaluation of Illness [LEVIL]). Extension phase; 2-week baseline with 24 weeks of HDx and 8-week washout.OutcomesPrincipal aim was to establish whether HDx therapy was associated with improved HRQoL, evidence of dose-dependant response, and whether effects were durable over time, using LEVIL.ResultsPatients with lower LEVIL scores (<70/100) at baseline showed improvement in overall HRQoL after 8 weeks of therapy with similar carryover effect. General well-being, energy, and sleep quality were improved significantly as a consequence of HDx therapy. There were no detrimental effects of HDx detected in patients with higher baseline HRQoL.LimitationsSmall nonrandomized sample size. The coronavirus disease 2019 pandemic interfered with the extension phase.ConclusionsDynamic PROM assessment effectively identified patients with lower HRQoL and higher symptom burden, demonstrating durable time/dose-dependent improvements across a range of symptom domains. The use of this instrument may allow targeted selection of patients most likely to benefit from HDx therapy and assist in monitoring response and defining effect size and treatment duration to allow optimal design of further definitive randomized controlled trials of this newly introduced technology.FundingBaxter Healthcare Canada.Trial registrationClinicalTrials.gov ID: NCT03640858.
| S-EPMC8664707 | biostudies-literature