High-Flux versus High-Retention-Onset Membranes: In vivo Small and Middle Molecules Kinetics in Convective Dialysis Modalities

2019 ◽  
Vol 49 (1-2) ◽  
pp. 8-15 ◽  
Author(s):  
Isis S.F. Cordeiro ◽  
Lilian Cordeiro ◽  
Carolina S. Wagner ◽  
Luiza Karla R.P. Araújo ◽  
Benedito J. Pereira ◽  
...  
Keyword(s):  
Total Mass ◽  
Crossover Trial ◽  
Maintenance Hemodialysis ◽  
High Flux ◽  
Serum Concentrations ◽  
Middle Molecules ◽  
Dialysis Membranes ◽  
Poor Outcomes ◽  
Beta 2 Microglobulin

Background: Patients undergoing maintenance hemodialysis (HD) exhibit increased levels of uremic toxins, which are associated with poor outcomes. Recently, new dialysis membranes have allowed clearance of solutes with higher molecular weight, without significant albumin losses high-retention-onset-HD (HRO-HD). Methods: Prospective crossover trial, in which 16 prevalent patients switched from high-flux HD (HF-HD) to online hemodiafiltration (olHDF) and HRO-HD for 4 weeks. The following variables were evaluated: pre- and post-dialysis serum concentrations of albumin, urea, phosphate (P), beta-2 microglobulin (β2M), and total mass (TM) extraction and dialyzer clearance of urea, P, and β2M. Results: Comparing HF-HD, olHDF, and HRO-HD, respectively, there were no differences regarding pre-dialysis serum concentrations of albumin (3.94 ± 0.36, 4.06 ± 0.22, and 3.93 ± 0.41 g/dL, p = 0.495), urea (166 ± 29, 167 ± 30, and 164 ± 27 mg/dL, p = 0.971), P (4.9 ± 2.1, 5.2 ± 1.6, and 4.9 ± 2.1 mg/dL, p = 0.879), and β2M (31.3 ± 7.1, 32.6 ± 8.6, and 33.7 ± 5.9 µg/mL, p = 0.646). β2M clearance was significantly lower in HF-HD in comparison to both olHDF and HRO-HD: 43 (37–53) versus 64 (48–85) mL/min, p = 0.013, and 69 (58–86) mL/min, p = 0.015, respectively. Post-dialysis β2M serum concentration was higher in HF-HD in comparison to olHDF and HRO-HD: 11.6 (9.6–12.4) vs. 5.7 (4.5–7.0) µg/mL, p = 0.001, and 5.6 (5.3–7.6) µg/mL, p = 0.001, respectively. TM extraction of urea, P, and β2M were similar across the 3 dialysis modalities. Conclusions: olHDF and HRO-HD were superior to HF-HD regarding β2M clearance, leading to lower post-dialysis β2M levels.

Influence of Dialysis Membranes on the Convective Transport of Middle Molecules

1986 ◽  
Vol 9 (6) ◽  
pp. 421-426 ◽  
Author(s):  
A.L. M. de Francisco ◽  
J. Gordillo ◽  
J.G. Cotorruelo ◽  
L. Ruiz ◽  
M. Gonzalez ◽  
...  
Keyword(s):  
High Performance ◽  
Convective Transport ◽  
Maintenance Hemodialysis ◽  
Gel Chromatography ◽  
High Flux ◽  
Solute Transfer ◽  
Effective Form ◽  
Middle Molecules ◽  
Dialysis Membranes ◽  
Chromatographic Profiles

Ultrafiltrates from 10 patients in chronic maintenance hemodialysis (7 males and 3 females) were obtained simultaneously using three different membranes: cuprophan, polyacrilonitrile and polysulfone. Middle molecules (MM) chromatographic profiles and total MM amount were determined by gel chromatography and high performance liquid chromatography. The convective transport of MM was similar and not membrane related. Hemofiltration, a predominantly convective solute transfer procedure using high flux membranes such as polyacrilonitrile and polysulfone, in which large amounts of fluids have to be ultrafiltered, is an effective form of MM removal.

scholarly journals A Pharmacokinetic Study Comparing the Clearance of Vancomycin during Haemodialysis Using Medium Cut-Off Membrane (Theranova) and High-Flux Membranes (Revaclear)

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 317
Author(s):  
Hussain Allawati ◽  
Linda Dallas ◽  
Sreejith Nair ◽  
Janine Palmer ◽  
Shaiju Thaikandy ◽  
...  
Keyword(s):  
Adverse Outcomes ◽  
High Flux ◽  
Serum Concentrations ◽  
Single Centre ◽  
Open Label ◽  
Median Percentage ◽  
Middle Molecules ◽  
Dialysis Membranes ◽  
Trough Concentrations ◽  
To Receive

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.

Testing protein permeability of dialysis membranes using SDS-PAGE

2002 ◽  
Vol 25 (5) ◽  
pp. 441-446 ◽  
Author(s):  
H. Mann ◽  
H. Melzer ◽  
A. Al-Bashir ◽  
X.Q. Xu ◽  
S. Stiller
Keyword(s):  
Protein Pattern ◽  
Human Kidney ◽  
Treatment Session ◽  
Retinol Binding Protein ◽  
High Flux ◽  
Sds Page ◽  
Silver Staining Method ◽  
Dialysis Membranes ◽  
Beta 2 Microglobulin ◽  
Protein Permeability

Background Permeability of dialysis membranes for high molecular weight compounds should be similar to that of the glomerular membrane in order to remove uremic toxins like the human kidney does. In order to evaluate permeability of high-flux dialysis membranes SDS-PAGE is applied for examination of filtrate of dialysers during routine dialysis with different membranes. Method SDS-PAGE analysis is performed with silver staining method according to the modification of Melzer (5) and consecutive laser densitometry. Results The protein pattern of filtrate from dialysis membranes is similar to that of the glomerular membrane containing IgG, transferrin, albumin, alpha-1-microglobulin, retinol binding protein and beta-2-microglobulin. Comparing different membranes there are considerable differences depending on cut-off, charge and adsorption capacity of the particular membrane. In all membranes tested permeability of proteins decreases during one treatment session. Conclusion Protein permeability of high-flux dialysis membranes is similar to the gloemerular membrane but modified according to pore-size, surface charge, adsorption and time on dialysis. In contrast to the glomerular membrane in each of the investigated membranes protein permeability decreases during function.

scholarly journals Effect of formaldehyde/bleach reprocessing on in vivo performances of high-efficiency cellulose and high-flux polysulfone dialyzers.

1998 ◽  
Vol 9 (3) ◽  
pp. 464-472
Author(s):  
B V Murthy ◽  
S Sundaram ◽  
B L Jaber ◽  
C Perrella ◽  
K B Meyer ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Creatinine Clearance ◽  
High Efficiency ◽  
Chronic Hemodialysis ◽  
High Flux ◽  
Urea Clearance ◽  
Small Molecular Weight ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Among the several disadvantages of reprocessed dialyzers is the concern that reuse could decrease the clearance of uremic toxins, leading to a decrease in the delivered dose of dialysis. To examine this possibility in the clinical setting, the clearances of small molecular weight solutes (urea and creatinine) and middle molecular weight substances (beta 2 microglobulin) were compared during dialysis with "high-efficiency" cellulose (T220L) and "high-flux" polysulfone (F80B) dialyzers reprocessed with formaldehyde and bleach. In a crossover study, six chronic hemodialysis patients were alternately assigned to undergo 21 dialysis treatments with a single T220L dialyzer or F80B dialyzer. Each patient was studied during first use (0 reuse), 2nd reuse (3rd use), and 5th, 10th, 15th, and 20th reuse of each dialyzer. Urea, creatinine, and beta 2 microglobulin clearances were measured at blood flow rates of 300 ml/min (Qb 300) and 400 ml/min (Qb 400). Total albumin loss into the dialysate was measured during each treatment. Urea or creatinine clearance of new T220L dialyzers was not significantly different from that of new F80B dialyzers at either Qb. Urea clearance of F80B dialyzers at Qb 300 decreased from 241 +/- 2 ml/min for new dialyzers to 221 +/- 5 ml/min after 20 reuses (P < 0.001), and Qb 400 from 280 +/- 4 ml/min for new dialyzers to 253 +/- 7 ml/min after 20 reuses (P = 0.001). Similarly, with reuse, creatinine clearance of F80B dialyzers also decreased at Qb 300 (P = 0.07) and Qb 400 (P = 0.03). In contrast, urea or creatinine clearance of T220L dialyzers did not decrease with reuse at either Qb. Urea clearance of T220L dialyzers was significantly higher than that of F80B at Qb 300 at the 5th, 10th, 15th, and 20th reuse (P < 0.001, = 0.005, = 0.004, and = 0.006, respectively), and Qb 400 at the 2nd, 5th, 10th, 15th, and 20th reuse (P = 0.04, 0.008, 0.03, 0.02, and 0.008, respectively). Beta 2 microglobulin clearance of T220L dialyzers was < 5.0 ml/min across the reuses studied. Beta 2 microglobulin clearance of F80B was < 5.0 ml/min for new dialyzers, but increased to 21.2 +/- 5.3 ml/min (Qb 300) and 23.6 +/- 3.3 ml/min (Qb 400) after 20 reuses (P < 0.001). Throughout the study, albumin was undetectable in the dialysate with T220L dialyzers. With F80B dialyzers, albumin was detected in the dialysate in four instances (total loss during dialysis, 483 mg to 1.467 g). In summary, the results of this study emphasize the greater need for information on dialyzer clearances during clinical dialysis, especially with reprocessed dialyzers. A more accurate knowledge of dialyzer performance in vivo would help to ensure that the dose of dialysis prescribed is indeed delivered to the patients.

scholarly journals P1102EVALUATION THE EFFICACY OF MEDIUM CUT- OFF MEMBRANE DIALYZERS AND COMPARISON WITH HIGH FLUX DIALYZERS IN CONVENTIONAL HEMODIALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Irena Rambabova Bushljetikj ◽  
Lada Trajcheska ◽  
Vladimir Pushevski ◽  
Sefedin Biljali ◽  
Trajan Balkanov
Keyword(s):  
Removal Rate ◽  
Uremic Toxins ◽  
High Flux ◽  
Removal Rates ◽  
Innovative Therapy ◽  
New Class ◽  
Number Of Patients ◽  
Middle Molecules ◽  
Dialysis Membranes

Abstract Background and Aims Hemodialysis (HD) is the most widely used modality of renal replacement therapy. The high-flux dialyzers in standard hemodialysis offer numerous benefits for ESRD patients, such as, increasing the uremic toxins removal and improving patients survival, reduced patients admission and morbidity. A new class of membranes, medium cut-off (MCO) membranes, has been designed to achieve better removal capacities for middle and large middle molecules, as well as to ensure the retention of albumin in hemodialysis (HD) treatments. We evaluated the removal efficacy of Theranova® in standard HD in comparison with standard high- flux HD. Method Four stable HD patients (M/F 1/4) were included in 12-weeks small observational pilot study in HD with Theranova® 400 (sup. 1.7 m2) and Theranova® 500 (sup. 2.0 m2) dialyzers. Each patient was assessed four times, T0 with standard high flux dialyzers, T1 at 1 month, T2 at second month and T3 at third month, by measuring pre and post-HD samples of: urea, creatinine, beta2-microglobilin (B2M), myoglobin, albumin and FLC-k, FLC-λ . Data are reported as mean ± standard deviation (SD). The removal rates of uremic toxins are expressed as percentages. Results The average removal rates for the uremic toxins with standard high-flux membranes were 18.4% for B2M, 14.3% for Myoglobin, 19.8 % for FLC-k and 17.4 % for FLC-λ. The data showed a higher average removal rate for all the uremic toxins with Theranova® dialyzers for B2M, Myoglobin, FLC-k and FLC-λ (62.7%, 56.9%, 63.5%, 54.6%, respectively) during the 3 months of follow up. The using of Theranova® dialyzers in standard HD was enough to significantly decrease the pre-dialysis value of Urea (17.72 ± 2.26 vs 13.75 ± 3.75, p=0.001), Creatinine (700.50 ± 315.07 vs 570.00 ± 206.64, p=0.021), B2M (40.90 ± 11.00 vs 29.00 ± 4.64, p=0.005), FLC-k (267.25 ± 113.28 vs 225.25 ± 100.62, p=0.018), FLC-λ (324.25 ± 116.12 vs 215.23 ± 64.44, p=0.011), Myoglobin ( 199.96 ± 124.41 vs 137.00 ± 83.14, p= 0.049). Finally, albumin retention was observed with Theranova® dialyzers, between T0 and T3 it increased significantly (40.50 ± 4.79 vs 42.25 ± 4.50, p=0.0001). Conclusion Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules in mid -term report. But the long term analysis and larger number of patients is necessary to evaluate a clinical significance of this innovative therapy.

scholarly journals Beta-2 microglobulin and all-cause mortality in the era of high-flux hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study

2020 ◽  
Author(s):  
Eiichiro Kanda ◽  
Daniel Muenz ◽  
Brian Bieber ◽  
Aleix Cases ◽  
Francesco Locatelli ◽  
...  
Keyword(s):  
Practice Patterns ◽  
Cox Regression ◽  
Urine Volume ◽  
High Flux ◽  
Reactive Protein ◽  
Middle Molecules ◽  
Dialysis Vintage ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Dialysis Outcomes

Abstract Background Beta-2 microglobulin (β2M) accumulates in hemodialysis (HD) patients, but its consequences are controversial, particularly in the current era of high-flux dialyzers. High-flux HD treatment improves β2M removal, yet β2M and other middle molecules may still contribute to adverse events. We investigated patient factors associated with serum β2M, evaluated trends in β2M levels and in hospitalizations due to dialysis-related amyloidosis (DRA), and estimated the effect of β2M on mortality. Methods We studied European and Japanese participants in the Dialysis Outcomes and Practice Patterns Study. Analysis of DRA-related hospitalizations spanned 1998–2018 (n = 23 976), and analysis of β2M and mortality in centers routinely measuring β2M spanned 2011–18 (n = 5332). We evaluated time trends with linear and Poisson regression and mortality with Cox regression. Results Median β2M changed nonsignificantly from 2.71 to 2.65 mg/dL during 2011–18 (P = 0.87). Highest β2M tertile patients (&gt;2.9 mg/dL) had longer dialysis vintage, higher C-reactive protein and lower urine volume than lowest tertile patients (≤2.3 mg/dL). DRA-related hospitalization rates [95% confidence interval (CI)] decreased from 1998 to 2018 from 3.10 (2.55–3.76) to 0.23 (0.13–0.42) per 100 patient-years. Compared with the lowest β2M tertile, adjusted mortality hazard ratios (95% CI) were 1.16 (0.94–1.43) and 1.38 (1.13–1.69) for the middle and highest tertiles. Mortality risk increased monotonically with β2M modeled continuously, with no indication of a threshold. Conclusions DRA-related hospitalizations decreased over 10-fold from 1998 to 2018. Serum β2M remains positively associated with mortality, even in the current high-flux HD era.

scholarly journals Medium cut-off dialyzer improves erythropoiesis stimulating agent resistance in a hepcidin-independent manner in maintenance hemodialysis patients: results from a randomized controlled trial

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeong-Hoon Lim ◽  
Yena Jeon ◽  
Ju-Min Yook ◽  
Soon-Youn Choi ◽  
Hee-Yeon Jung ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Transferrin Saturation ◽  
Resistance Index ◽  
Serum Levels ◽  
Estimating Equation ◽  
Maintenance Hemodialysis ◽  
High Flux ◽  
Independent Manner ◽  
Tnf Α ◽  
Middle Molecules

Abstract 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 significant decrease in the ESA dose, weight-adjusted ESA dose, and ERI compared to the high-flux group at 12 weeks (p < 0.05). The generalized estimating equation models revealed significant interactions between groups and time for the ESA dose, weight-adjusted ESA dose, and ERI (p < 0.05). Serum iron and transferrin saturation were higher in the MCO group at 12 weeks (p < 0.05). The MCO group showed a greater reduction in TNF-α and lower serum TNF-α level at 12 weeks compared to the high-flux group (p < 0.05), whereas no differences were found in the reduction ratio of hepcidin and serum levels of erythropoietin, erythroferrone, soluble transferrin receptor and hepcidin between groups. HD with MCO dialyzer improves ESA resistance over time compared to high-flux HD in maintenance HD patients. The MCO dialyzer provides superior removal of the inflammatory cytokine and thus improves iron metabolism in a hepcidin-independent manner.

Beta-2 Microglobulin Removal by Immunoextraction and Passive Adsorption in High-Flux Dialyzers

2011 ◽  
Vol 11 ◽  
pp. 35-44
Author(s):  
Michael L. Branham ◽  
T. Govender ◽  
Edward A. Ross
Keyword(s):  
Small Volume ◽  
Membrane Surface ◽  
High Flux ◽  
Cellulose Diacetate ◽  
Passive Adsorption ◽  
Circulating Antibodies ◽  
Dialysis Membranes ◽  
Beta 2 ◽  
Beta 2 Microglobulin

The objectives in this study were to compare the removal of 2-M via different dialyzers (high- and low flux) under equilibrium or sink conditions, wherein there was highly selective antibody-based facilitated transport into a small volume dialysate reservoir. Using an in vitro haemodialysis model we perfused high-flux polymethylmethacrylate (PMMA), high-flux cellulose diacetate (CDA), and a low-flux polysulfone (PSF) membranes with known amounts of 2-M through the intracapillary space. Anti-2-M antibodies added to the extracapillary space were shown to create sink conditions across the membrane when its pore size is sufficiently large for diffusion and if 2-M is not strongly adsorbed to the membrane surface. Our results indicate that 2-M (~12kDa) does not penetrate low-flux dialyzers and that its adsorption to intracapillary PSF surfaces does not substantially affect clearance. 2-M strongly adsorbed to high-flux PMMA dialyzers (ko = 0.0271+0.002 min-1), but without significant clearance enhancement due to circulating antibodies. A significant clearance enhancement (101.2%+24.89) for 2-M due to immunoextraction was observed in the high-flux cellulose acetate dialyzers, but without passive adsorption to the surface. These studies demonstrate the utility of in vitro haemodialysis experiments to elucidate midsize molecule clearance in dialysis membranes under controlled conditions. The use of anti-2-M antibodies as dialysate additives might be feasible in the removal of 2-M from whole blood, highlighting the advantages of selective antibody-based extraction of disease-causing toxins into potentially simple extracorporeal devices with small volume receiver compartments.

scholarly journals Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 Dialyzer

2020 ◽  
Vol 15 (9) ◽  
pp. 1310-1319 ◽  
Author(s):  
Daniel E. Weiner ◽  
Luke Falzon ◽  
Line Skoufos ◽  
Angelito Bernardo ◽  
Werner Beck ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Serum Albumin Level ◽  
Albumin Level ◽  
Reduction Ratio ◽  
Light Chains ◽  
Maintenance Hemodialysis ◽  
High Flux ◽  
Efficacy And Safety ◽  
End Point ◽  
Middle Molecules

Background and objectivesExpanded hemodialysis therapy enabled by medium cut-off membranes may promote greater clearance of larger middle molecules that comprise putative uremic solutes than conventional high-flux dialysis. This randomized trial evaluated the efficacy and safety of hemodialysis treatment with a medium cut-off dialyzer.Design, setting, participants, & measurementsClinically stable patients on maintenance hemodialysis were randomized to receive dialysis with either a medium cut-off dialyzer (Theranova 400) or a high-flux dialyzer (Elisio-17H) over 24 weeks of treatment. The primary safety end point was the predialysis serum albumin level after 24 weeks of treatment. The primary efficacy end point was the reduction ratio of free λ light chains at 24 weeks of treatment.ResultsAmong 172 patients on maintenance hemodialysis, mean age was 59±13 years, 61% were men, 40% were Black, and mean dialysis vintage was 5±4 years. Of the 86 patients randomized to each dialyzer, 65 completed the trial in each group. The reduction ratio for the removal of free λ light chains was significantly higher in the Theranova 400 group compared with the Elisio-17H group after 4 weeks (39% versus 20%) and 24 weeks (33% versus 17%; both P<0.001). Among secondary end points, the Theranova 400 group demonstrated significantly larger reduction ratios at 4 and 24 weeks for complement factor D, free κ light chains, TNFα, and β2-microglobulin (P<0.001 for all), but not for IL-6. Predialysis serum albumin levels were similar between groups after 24 weeks (4 g/dl with the Theranova 400 and 4.1 g/dl with the Elisio-17H), consistent with noninferiority of the Theranova 400 dialyzer in maintaining predialysis serum albumin levels after 24 weeks of treatment.ConclusionsHemodialysis therapy with the Theranova 400 dialyzer provides superior removal of larger middle molecules, as exemplified by free λ light chains, compared with a similar size high-flux dialyzer, while maintaining serum albumin level.Clinical Trial registry name and registration numberA Multi-Center, Prospective, Randomized, Controlled, Open-Label, Parallel Study to Evaluate the Safety and Efficacy of the Theranova 400 Dialyzer in End Stage Renal Disease (ESRD) Patients, NCT03257410.

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