Dataset Information

Effects of Medium Cut-Off Versus High-Flux Hemodialysis Membranes on Biomarkers: A Systematic Review and Meta-Analysis.

ABSTRACT:

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 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.

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.

SUBMITTER: Kandi M

PROVIDER: S-EPMC8777328 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:BACKGROUND:Clinical practice guidelines regarding the use of high-flux haemodialysis membranes vary widely. OBJECTIVES:We aimed to analyse the current evidence reported for the benefits and harms of high-flux and low-flux haemodialysis. SEARCH METHODS:We searched Cochrane Renal Group's specialised register (July 2012), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1948 to March 2011), and EMBASE (1947 to March 2011) without language restriction. SELECTION CRITERIA:We included randomised controlled trials (RCTs) that compared high-flux haemodialysis with low-flux haemodialysis in people with end-stage kidney disease (ESKD) who required long-term haemodialysis. DATA COLLECTION AND ANALYSIS:Data were extracted independently by two authors for study characteristics (participants and interventions), risks of bias, and outcomes (all-cause mortality and cause-specific mortality, hospitalisation, health-related quality of life, carpal tunnel syndrome, dialysis-related arthropathy, kidney function, and symptoms) among people on haemodialysis. Treatment effects were expressed as a risk ratio (RR) or mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. MAIN RESULTS:We included 33 studies that involved 3820 participants with ESKD. High-flux membranes reduced cardiovascular mortality (5 studies, 2612 participants: RR 0.83, 95% CI 0.70 to 0.99) but not all-cause mortality (10 studies, 2915 participants: RR 0.95, 95% CI 0.87 to 1.04) or infection-related mortality (3 studies, 2547 participants: RR 0.91, 95% CI 0.71 to 1.14). In absolute terms, high-flux membranes may prevent three cardiovascular deaths in 100 people treated with haemodialysis for two years. While high-flux membranes reduced predialysis beta-2 microglobulin levels (MD -12.17 mg/L, 95% CI -15.83 to -8.51 mg/L), insufficient data were available to reliably estimate the effects of membrane flux on hospitalisation, carpal tunnel syndrome, or amyloid-related arthropathy. Evidence for effects of high-flux membranes was limited by selective reporting in a few studies. Insufficient numbers of studies limited our ability to conduct subgroup analyses for membrane type, biocompatibility, or reuse. In general, the risk of bias was either high or unclear in the majority of studies. AUTHORS' CONCLUSIONS:High-flux haemodialysis may reduce cardiovascular mortality in people requiring haemodialysis by about 15%. A large well-designed RCT is now required to confirm this finding.

Project description:BackgroundRegional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques.MethodsIn this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD.ResultsMean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p<0.001). For myoglobin (8.0±4.5 ml/min vs. 0.2±3.6 ml/min, p<0.001) and IL-6 (1.5±4.3 vs. -2.5±3.5 ml/min, p = 0.002) a higher mean plasma clearance using high-cut-off dialyzer could be detected too, but no difference for urea, creatinine and albumin could be observed concerning this parameter between the two groups.ConclusionCVVHD using a high cut-off dialyzer results in more effective middle molecule clearance than that with high-flux dialyzer.Trial registrationGerman Clinical Trials Register (DRKS00005254, registered 26th November 2013).