Medium cut-off dialyzer improves erythropoiesis stimulating agent resistance in a hepcidin-independent manner in maintenance hemodialysis patients: results from a randomized controlled trial.
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SUBMITTER: Lim JH
PROVIDER: S-EPMC7524751 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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Medium cut-off dialyzer improves erythropoiesis stimulating agent resistance in a hepcidin-independent manner in maintenance hemodialysis patients: results from a randomized controlled trial.
Lim Jeong-Hoon JH Jeon Yena Y Yook Ju-Min JM Choi Soon-Youn SY Jung Hee-Yeon HY Choi Ji-Young JY Park Sun-Hee SH Kim Chan-Duck CD Kim Yong-Lim YL Cho Jang-Hee JH
Scientific reports 20200929 1
The response to erythropoiesis stimulating agents (ESAs) is affected by inflammation linked to middle molecules in hemodialysis (HD) patients. We evaluated the effect of a medium cut-off (MCO) dialyzer on ESA resistance in maintenance HD patients. Forty-nine patients who underwent high-flux HD were randomly allocated to the MCO or high-flux group. The primary outcome was the changes of erythropoietin resistance index (ERI; U/kg/wk/g/dL) between baseline and 12 weeks. The MCO group showed signifi ...[more]
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Project description:BACKGROUND AND OBJECTIVES: A 1-year multicenter prospective randomized controlled study was conducted on the effects of vitamin E-bonded polysulfone dialyzers on erythropoiesis-stimulating agent response in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Major inclusion criteria were use of high-flux polysulfone dialyzers with 50-70 ml/min ?2-microglobulin clearance over 3 months, transferrin saturation over 20%, same erythropoiesis-stimulating agent for over 3 months, and hemoglobin at 10-12 g/dl. Hemodialysis patients were placed in four interventional groups: two hemoglobin ranges (10.0-10.9 or 11.0-11.9 g/dl) and two dialyzers. Patients were randomly assigned by central registration to a vitamin E-bonded polysulfone dialyzers or polysulfone control group. Primary end point was relative erythropoiesis resistance index at baseline between groups at 12 months. Erythropoiesis resistance index was defined as total weekly erythropoiesis-stimulating agent dose divided by hemoglobin. RESULTS: There were no statistically significant differences in age or sex. There was no significant difference in relative erythropoiesis resistance index between vitamin E-bonded polysulfone dialyzers and control groups at 12 months (vitamin E-bonded polysulfone dialyzers: 1.1, control: 1.3). The vitamin E-bonded polysulfone dialyzers group showed better relative erythropoiesis resistance index than the control group at 11.0-11.9 g/dl hemoglobin (vitamin E-bonded polysulfone dialyzers: 1.0, control: 1.4 at 12 months, significant difference) but no difference at 10.0-10.9 g/dl hemoglobin. CONCLUSIONS: The overall relative erythropoiesis resistance index showed no difference between the vitamin E-bonded polysulfone dialyzers and control groups, although the change in relative erythropoiesis resistance index differed according to hemoglobin level.
| S-EPMC3675844 | biostudies-literature
Project description:African Americans require higher doses of erythropoiesis-stimulating agents (ESAs) during dialysis to manage anemia, but the influence of sickle cell trait and other hemoglobinopathy traits on anemia in dialysis patients has not been adequately evaluated. We performed a cross-sectional study of a large cohort of adult African-American hemodialysis patients in the United States to determine the prevalence of hemoglobinopathy traits and quantify their influence on ESA dosing. Laboratory and clinical data were obtained over 6 months in 2011. Among 5319 African-American patients, 542 (10.2%) patients had sickle cell trait, and 129 (2.4%) patients had hemoglobin C trait; no other hemoglobinopathy traits were present. Sickle cell trait was more common in this cohort than the general African-American population (10.2% versus 6.5%-8.7%, respectively, P<0.05). Among 5002 patients (10.3% sickle cell trait and 2.4% hemoglobin C trait) receiving ESAs, demographic and clinical variables were similar across groups, with achieved hemoglobin levels being nearly identical. Patients with hemoglobinopathy traits received higher median doses of ESA than patients with normal hemoglobin (4737.4 versus 4364.1 units/treatment, respectively, P=0.02). In multivariable analyses, hemoglobinopathy traits associated with 13.2% more ESA per treatment (P=0.001). Within subgroups, sickle cell trait patients received 13.2% (P=0.003) higher dose and hemoglobin C trait patients exhibited a similar difference (12.9%, P=0.12). Sensitivity analyses using weight-based dosing definitions and separate logistic regression models showed comparable associations. Our findings suggest that the presence of sickle cell trait and hemoglobin C trait may explain, at least in part, prior observations of greater ESA doses administered to African-American dialysis patients relative to Caucasian patients.
| S-EPMC3968502 | biostudies-literature
Project description:ObjectiveHyporesponsiveness to erythropoiesis-stimulating agent (ESA) may be associated with protein-energy wasting. We investigated the relationship of the ESA resistance index (ERI) and the geriatric nutritional risk index (GNRI) for cardiovascular mortality in hemodialysis (HD) patients.MethodsA total of 180 maintenance HD patients were enrolled. The patients were stratified by the GNRI of 91.2, a previously reported cut-off value, and the ERI of 13.7 (IU/week/kg/g/dL), a cut-off value for predicting cardiovascular-specific mortality, and they were classified into four groups (group 1[G1]: higher GNRI and lower ERI, G2: higher GNRI and higher ERI, G3: lower GNRI and lower ERI, G4: lower GNRI and higher ERI).ResultsThe ERI was independently associated with the GNRI (β = -0.271, p = 0.0005). During a median follow-up of 4.6 years, higher ERI and lower GNRI were independently associated with cardiovascular mortality, respectively (adjusted hazard ratio [aHR], 3.10; 95% confidence interval [CI], 1.31-7.34, and aHR, 6.64; 95%CI, 2.60-16.93, respectively). The 7-year survival rates were 96.1%, 70.3%, 77.3%, and 50.1% in G1, G2, G3, and G4, respectively. The aHR values for G4 versus G1 were 12.63 (95%CI, 3.58-44.59). With regards to model discrimination, adding the GNRI alone, the ERI alone, and both to the traditional risk model significantly improved the net reclassification improvement by 0.421, 0.662, and 0.671, respectively. Similar results were obtained for all-cause mortality.ConclusionThe ERI was independently associated with the GNRI, and could predict cardiovascular mortality in HD patients. Moreover, the combination of GNRI and ERI could improve the predictability for cardiovascular mortality.
| S-EPMC7810304 | 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.
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Project description:African-American patients with end-stage renal disease have historically lower hemoglobin concentrations and higher requirements of erythropoiesis-stimulating agent (ESA). While disparities in health-care access may partially explain these findings, the role of variant hemoglobin, such as sickle trait, has not been investigated. To clarify this, we evaluated 154 African-American patients receiving in-center hemodialysis with available hemoglobin phenotyping. The primary exposure was any abnormal hemoglobin variant and the primary outcome of higher-dose ESA was defined as a dose of 6500 or more units per treatment. Logistic regression assessed the association between variant hemoglobin and higher-dose ESA. Covariates included age, gender, diabetes, iron parameters, intravenous iron dose, parathyroid hormone, albumin, phosphorus, body mass index, vascular access type, hospitalization/missed treatments, smoking status, alcohol abuse, and gastrointestinal bleeding. Of 33 patients with variant hemoglobin, 24 had HbAS and 9 had HbAC. Univariate odds of higher-dose ESA among those with hemoglobin variants were twice that of those with the normal HbAA phenotype (odds ratio 2.05). In multivariate models, the likelihood of higher-dose ESA had an odds ratio of 3.31 and the nature of this relationship did not change in Poisson regression or sensitivity analyses. Hence, our findings may explain, in part, the difference in ESA dosing between Caucasians and African-Americans with end-stage renal disease but await further study.
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Project description:Residence at higher altitude has been associated with improved anemia parameters and lower mortality rates among end-stage renal disease (ESRD) patients. However, these associations were observed prior to the 2011 shift in erythropoiesis-stimulating agent (ESA) dosing. To determine the impact of altitude on contemporary ESRD patients, a retrospective observational analysis was conducted in which patients were ascribed to one of four altitude categories as of 1 Jan 2012 and outcomes were assessed during 2012. Associations between altitude category and outcomes were estimated using generalized linear mixed models, adjusted for covariates that differed at baseline. Patients at higher altitude were less likely to receive ESA treatment, and dose was 723 U/treatment (95?% confidence interval [CI]: 544, 834) lower in the highest altitude category compared to the lowest category. The proportion of patients using IV iron decreased with increasing altitude category. Patients in the highest two categories had greater mean hemoglobin values (+0.15 and +0.23 g/dL) than the lowest. Mortality was lower for patients in the highest altitude category compared to those in the lowest (incidence rate ratio 0.73; 95?% CI: 0.63, 0.88), although their rate of missed dialysis treatments was slightly higher. This study confirms that, in the context of current anemia management practices, high altitude is associated with higher hemoglobin and lower mortality, despite lower utilization of ESA and IV iron.
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Project description:Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory- and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7 ± 13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory- and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p<0.001), hsCRP (p<0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p<0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance.
| S-EPMC3396629 | biostudies-literature
Project description:Ferric pyrophosphate citrate (FPC) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin. The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent (ESA) use and maintain hemoglobin in hemodialysis patients. This 9-month, randomized, placebo-controlled, double-blind, multicenter clinical study included 103 patients undergoing hemodialysis 3-4 times weekly. The FPC group received dialysate containing 2??mol/l of iron. The placebo group received standard dialysate. A blinded central anemia management group facilitated ESA dose adjustments. Intravenous iron was administered according to the approved indication when ferritin levels fell below 200??g/l. The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment. Secondary end points included intravenous iron use and safety. At the end of treatment, there was a significant 35% reduction in prescribed ESA dose in FPC-treated patients compared with placebo. The FPC patients used 51% less intravenous iron than placebo. Adverse and serious adverse events were similar in both groups. Thus, FPC delivered via dialysate significantly reduces the prescribed ESA dose and the amount of intravenous iron needed to maintain hemoglobin in chronic hemodialysis patients.
| S-EPMC4653585 | biostudies-literature
Project description:BackgroundCompared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules.MethodsIn 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.ResultsMCO 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.ConclusionsMCO 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.
| S-EPMC5837492 | biostudies-literature
Project description:The medium cut-off (MCO) dialyzer has shown good clearance of large middle molecules, but its long-term effects are unclear. We investigated whether MCO hemodialysis (HD) over one year could reduce middle molecule levels and cell-free hemoglobin (CFH), without albumin loss. A prospective cohort study in 57 hemodialysis patients was conducted. The patients were assigned to the MCO dialyzer group or the high-flux dialyzer group, according to the HD machine they used. The reduction ratio (RR) and one-year changes in small and middle molecules and CFH were analyzed. Over a 12-month follow-up, MCO HD did not reduce the serum levels of middle molecules (lambda free light chain [FLC], from 135.7 ± 39.9 to 132.0 ± 39.1 mg/L; kappa FLC, from 168.2 ± 58.5 to 167.7 ± 65.8 mg/L; ?2-microglobulin, from 25.6 ± 9.6 to 28.4 ± 4.8 mg/L) or albumin (from 3.96 ± 0.31 to 3.94 ± 0.37 g/dL). MCO HD provided excellent RR of lambda FLC (49.3 ± 10.3%), kappa FLC (69.6 ± 10.4%) and ?2-microglobulin (80.9 ± 7.3%), compared to high-flux HD. CFH was also removed well during an MCO HD session (RR of CPH, 85.5 [78.7-97.3] %), but long-term change was not significant (from 57.8 [46.2-79.1] to 62.0 [54.6-116.7] mg/L). The MCO dialyzer can be used effectively and safely in conventional HD settings, but long-term effects on large middle molecules and CFH were not significant. Further studies are needed to verify clinical benefits of the MCO dialyzer.
| S-EPMC6660073 | biostudies-literature