High-flux Dialysis Research Articles

Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients

BackgroundRemoval of uraemic toxins is inadequate using current dialysis strategies. A new class of dialysis membranes have been developed that allow clearance of larger middle molecules. The REMOVAL-HD study (a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients) will address safety, efficacy and the impact on patient-centred outcomes with the use of a mid cut-off (MCO) dialyser in a chronic haemodialysis (HD) population.MethodsREMOVAL-HD is an open label, prospective, non-randomised, single-arm, multi-centre device study in 85 chronic HD participants. All visits will be conducted during regular HD sessions and participants will undergo a 1 month wash-in period using a standardised high flux dialyser, 6 months of intervention with a MCO dialyser and 1 month of wash-out using a high flux dialyser. The primary endpoint is change in pre-dialysis concentrations of serum albumin, with secondary endpoints including the efficacy of clearance of free light chains and β-2 microglobulin, and patient-centred outcomes including quality of life, symptom burden, functional status, nutritional status, hospitalisation and death.DiscussionMCO dialysers are a novel form of HD membrane. The REMOVAL-HD study is a pivotal study designed to monitor the immediate and medium-term effects following exposure to this dialyser.Trial registrationAustralian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482. Date of registration - 21/06/2016.

Comparison of the effects of different blood purification methods on inflammatory cytokines clearance in patients with maintenance hemodialysis

Objective To compare the effects of different ways of blood purification on inflammatory cytokines clearance in patients with maintenance hemodialysis. Methods The clinical data of 50 patients with maintenance hemodialysis were retrospectively analyzed.The low flux dialysis, high flux dialysis were used respectively, and the changes of hypersensitive C-reactive protein(hs-CRP), tumor necrosis factor alpha(TNF-α), interleukin 1(IL-1), interleukin 6(IL-6) after dialysis were compared between the two methods. Results After low flux dialysis, the hs-CRP, TNF-α, IL-1, IL-6 levels were (6.58±3.69)mg/L, (1.54±0.42)g/L, (105.46±8.20)ng/L, (27.58±6.83)ng/L, respectively, which after high flux dialysis were (2.93±1.85)mg/L, (1.13±0.27)g/L, (97.21±7.14)ng/L, (20.35±5.76)ng/L, respectively, the differences were statistically significant(t=6.253, 5.806, 5.365, 5.806, all P<0.05). Conclusion Compared with the low flux dialysis, high flux dialysis is more effective in inflammatory cytokines clearance in patients with maintenance hemodialysis. Key words: Hemodiafiltration; C-Reactive protein; Tumor necrosis factor-alpha; Interleukins; Controlled clinical trial

Exploring the Clinical Relevance of Providing Increased Removal of Large Middle Molecules.

Dialysis technologies have continued to advance over recent decades; however, these advancements have not always been met with improved patient outcomes. In part, the high morbidity and mortality associated with dialysis have been attributed to a group of uremic toxins, which are described as "difficult to remove." With a new generation of hemodialysis membranes now making meaningful clearance of these molecules possible, it is an apt time to review the clinical relevance of these middle molecules. Our review describes the developments in membrane technology that enable the removal of large middle molecules (molecular mass >15 kD) that is limited with high-flux dialysis membranes. Of the known 58 middle molecules, a literature search identified 27 that have molecular mass >15 kD. This group contains cytokines, adipokines, hormones, and other proteins. These molecules are implicated in chronic inflammation, atherosclerosis, structural heart disease, and secondary immunodeficiency in the literature. Single-center safety and efficacy studies have identified that use of these membranes in maintenance dialysis populations is associated with limited loss of albumin and increased clearance of large middle molecules. Larger, robustly conducted, multicenter studies are now evaluating these findings. After completion of these safety and efficacy studies, the perceived clinical benefits of providing clearance of large middle molecules must be assessed in rigorously conducted, randomized clinical studies.

Evaluation of the efficacy of a medium cut-off dialyser and comparison with other high-flux dialysers in conventional haemodialysis and online haemodiafiltration.

ABSTRACTBackgroundOnline haemodiafiltration (OL-HDF) has been shown to reduce all-cause mortality versus conventional haemodialysis (HD); however, it is not always available. In these situations, a novel class of membranes with a higher pore size, medium cut-off (MCO) dialysers, could be promising. The aim of this study is to evaluate the efficacy of an MCO dialyser in the removal of small and medium-size molecules and compare it with standard high-flux (HF) dialysers in HD and OL-HDF.MethodsIn this crossover study, 18 prevalent HD patients were studied in three single mid-week dialysis treatments during three consecutive weeks as follows: first week with OL-HDF with a standard HF dialyser, second week with conventional HD with a standard HF dialyser and third week with conventional HD with an MCO dialyser. Reduction ratios (RRs) of different-sized molecules and albumin losses were collected for the different dialysers.ResultsMCO HD provided a greater reduction of middle and larger middle molecules compared with standard HF HD [rate reduction (RR) β2-microglobulin 74.7% versus 69.7%, P=0.01; RR myoglobin 62.5% versus 34.3%, P=0.001; RR prolactin 60% versus 32.8%, P=0.001; RR α1-glycoprotein 2.8% versus −0.1%, P=0.01]. We found no difference in the clearance of small and larger middle molecules comparing MCO HD with OL-HDF. Albumin losses were 0.03 g/session with MCO HD and 3.1 g/session with OL-HDF (P=0.001).ConclusionMCO HD is superior to standard HF HD in the removal of middle and larger middle molecules and it is not inferior to OL-HDF in the clearance of small and larger middle molecules. Thus it could be an alternative in patients in which it is not possible to perform OL-HDF.

Removal of vancomycin administered during dialysis by a high‐flux dialyzer

Hemodialysis patients frequently receive vancomycin for treatment of gram-positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high-flux polyamide dialyzers. This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high-flux (Polyflux 24R) dialyzer (Phase 2). There was a three-week washout period between phases. Serial serum vancomycin concentrations were used to determine the removal of vancomycin when administered during dialysis. Dialysis removed 35 ± 15% (range 18-56%) of the vancomycin dose when administered during the last hour of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0-44.5 hours from the start of infusion were similar between the two phases (AUCPhase 1 884 ± 124 mg-hr/L, mean ± SD; AUCPhase 2 856 ± 208 mg-hr/L; P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis treatment following vancomycin administration were also similar between the two phases (13.1 ± 2.7 mg/L in Phase 1 and 12.3 ± 3.3 mg/L in Phase 2; P=0.55). When using a polyarylethersulfone, polyvinylpyrrolidone, and polyamide high-flux HD membrane with a 24R Polyflux dialyzer, vancomycin can be administered during the last hour of dialysis if the dose that is prescribed for intra-dialysis dosing is empirically increased to account for intra-dialytic drug removal.

Removal of stabilizers from human serum albumin by adsorbents and dialysis used in blood purification.

IntroductionHuman serum albumin (HSA) is a monomeric multi-domain protein that possesses an extraordinary binding capacity. It plays an important role in storing and transporting endogenous substances, metabolites, and drugs throughout the human circulatory system. Clinically, HSA is used to treat a variety of diseases such as hypovolemia, shock, burns, hemorrhage, and trauma in critically ill patients. Pharmaceutical-grade HSA contains the stabilizers sodium caprylate and N-acetyltryptophanate to protect the protein from oxidative stress and to stabilize it for heat treatment which is applied for virus inactivation.Material and methodsThe aim of this study was to determine if the two stabilizers can be depleted by adsorbent techniques. Several, adsorbents, some of them are in clinical use, were tested in batch and in a dynamic setup for their ability to remove the stabilizers. Furthermore, the removal of the stabilizers was tested using a pediatric high flux dialyzer.ResultsThe outcome of this study shows that activated charcoal based adsorbents are more effective in removal of N-acetylthryptophanate, whereas polystyrene based adsorbents are better for the removal of caprylate from HSA solutions. An adsorbent cartridge which contains a mix of activated charcoal and polystyrene based material could be used to remove both stabilizers effectively. After 4 hours treatment with a high flux dialyzer, N-acetyltryptophanate was totally removed whereas 20% of caprylate remained in the HSA solution.

The Influence of Colloid Osmotic Pressure on Hydrostatic Pressures in High- and Low-Flux Hemodialyzers.

The aim of this study was to examine the relationship between hydrostatic trans-membrane pressure (TMPh ) and colloid osmotic pressure (COP) in low-flux (LF) and high-flux (HF) dialyzers. Hydrostatic pressures were measured in dialyzers distinguished by their ultrafiltration coefficient Kuf (16 and 85 mL/h/mm Hg) under constant dialysate flow and variable blood flow (Qb ) ranging from 0 to 400 mL/min using (i) alginate (70 kDa) dissolved in dialysate, (ii) diluted, undiluted, and concentrated plasma, or (iii) whole blood at different hematocrit, all in absence of ultrafiltration (UF). For a given fluid, TMPh linearly increased with increasing Qb . The intercept of the linear TMPh to Qb relationship correlated with measured COP with an average bias of 1.00 ± 2.26 mm Hg and a concordance correlation coefficient of 0.98. The slope of the linear TMPh to Qb relationship increased with increasing sample viscosity and was much larger in HF dialyzers under otherwise identical operating conditions, most likely because of increased internal filtration. The TMPh to Qb relationship measured in dialyzers in absence of UF can be described by the intercept related to measured COP and the slope related to internal filtration. This relationship could be of interest to estimate internal filtration and COP under in vivo conditions.

Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis modalities: a meta-analysis of published studies.

Background Recent meta-analyses suggest that higher removal of beta-2 microglobulin (β2M) with either high-flux (HFD) dialysis or hemodiafiltration (HDF) may be associated with decreased total and cardiovascular mortality in dialysis patients. However, there are limited data about the performance of high flux dialyzers and/or convective therapies in removing β2M. Methods This is a random effects meta-analysis and meta-regression of data extracted from randomized controlled trials and observational studies in hemodialysis, hemofiltration and HDF regarding the efficiency of high flux dialyzers to remove β2M. Studies were searched using ProQuest in SCOPUS, EMBASE and MEDLINE. Results We included 69 studies from 1 January 2001 to 12 June 2017 on 1879 patients with 6771 available measurements. Average β2M clearance was 48.75 mL/min [95% confidence interval (CI) 42.50-55.21] for conventional HF dialysis, and 87.06 mL/min (95% CI 75.08-99.03) for convective therapies (hemofiltration and HDF) with substantial heterogeneity among studies [P (Q) ≤ 0.001]. In multivariable meta-regression analyses, we found significantly higher β2M clearance for polyarylethersulfone dialyzers when used for HFD and polysulfone membranes in convective therapies. However, the mass of β2M removed into the dialysate did not depend on membrane material. Adjusted dialysate-side (-22.279, 95% CI -9.8 to -34.757, P < 0.001) β2M clearances were significantly lower than whole blood clearances, suggesting that adsorption contributes substantially to β2M removal. Higher Kuf, blood flow and substitution fluid rates but not dialysate flow rates were associated with statistically significant and clinically meaningful elevation in β2M clearance from the body independent of the dialysis modality. Conclusions Membrane composition and characteristics, modality (convective versus diffusive), blood flow rates and substitution fluid rates in HDF play a significant role in the efficient removal of β2M from the body in both diffusive and convective dialysis.

Effect of Combined Peritoneal Dialysis and Hemodialysis on Health-Related Quality of Life.

In Japan, combined peritoneal dialysis (PD) and hemodialysis (HD) therapy is performed widely as an established modality of renal replacement therapy. This combination therapy is indicated for patients who cannot maintain adequate solute clearance using a standard PD prescription, or those who have uremic symptoms or a state of persistent fluid overload. A common treatment schedule for combined PD + HD therapy consists of 5 days of PD and one HD session per week. A 4- to 5-h HD session is performed with a high-flux membrane dialyzer. On the HD day and the following day, patients are released from bag exchange for PD, defined as a PD holiday. The effectiveness of combined PD + HD therapy for solute clearance and fluid management has been recognized, but only a few reports have considered whether combined PD + HD therapy improves health-related quality of life (HRQOL) in uremic PD patients. We prospectively assessed clinical parameters and HRQOL by using the Short Form Health Survey-Version 2 (SF-36) and the Kidney Disease Quality of Life Instrument-Short Form (KDQOL-SF) before and 1 year after initiation of combined PD + HD therapy in 10 Japanese PD patients who could not achieve adequate solute clearance or fluid volume control. After starting combined PD + HD therapy, body weight and urine volume decreased and renal anemia and azotemia improved. Evaluation of HRQOL with the SF-36 showed improvement in physical function (72.9 ± 12.4 vs. 79.1 ± 12.4, p < 0.05). KDQOL scores for the symptoms/problems (68.3 ± 12.2 vs. 80.2 ± 17.6, p < 0.05) and effect of kidney disease (77.2 ± 12.1 vs. 82.8 ± 14.5, p < 0.05) showed significant improvement. Combined PD + HD therapy improved fluid volume management and uremic symptoms, leading to better HRQOL. Key Messages: Combined therapy improved fluid management and uremic symptoms, leading to better HRQOL.

Capacity Characterized by a Medium Cut

Introduction: The adsorbing capacity of membranes can be considered the third dimension of the depurative action of dialysis: diffusion, convection and adsorption. Some metabolites are almost totally bound to albumin, so, regardless of their molecular weight, removal with low flux or high flux dialysis membranes becomes difficult if not impossible. The aim of our work was to evaluate the adsorptive efficacy as well as the depurative of a new membrane with a medium cut-off: Theranova 400, PAES / PVP membrane with surface 1.7 m2 Baxter. Materials and methods: Four patients in chronic three-weekly dialysis were evaluated for over 6 months, treated with the Theranova 400 dialyzer filter, for 6 dialysis bicarbonate sessions. In every piece, blood tests were performed at the beginning and end of dialysis, for the first 3 dialysis and at the third dialysis of the second week, to evaluate besides the purification of the main standard parameters, also the removal of medium molecular weight solutes such as myoglobin, beta2 microglobulin and solutes such as indoxyl sulfate (F IXS) and pcresol (F PCS) which represent less than 10% of the free fraction being bound to albumin for more than 90% of their total concentration (T IXS and T PCS). IXS and PCS were also measured at the biginning of the third dialysis session of the week , in other 130 ESRD patients treated with various membranes . The statistical differences, before and after dialysis, were calculated with the Student’s t test for paired data. For the comparison of the values between Theranova and other membranes the Mann Whitney U Test was used for nonparametric data. Results: At the end of the 6 4-h hemodialysis sessions there was a significant decrease in both the low molecular weight parameters with a good KT/V and a urea clearance close to 300 ml/min. Mean MW concentrations were reduced by 50-75%, while F IXS, T IXS, F PCS and T PCS were reduced by more than 20%. The predialytic values of the last dialysis of the week tended to be higher and in some statistically significant in all the other membranes compared to Theranova. Conclusions: In addition to the high diffusional purifying capacity, the membrane shows a marked adsorptive capacity demonstrated by the effective removal of metabolites linked to albumin and therefore more difficult to remove. It will be interesting to follow in time the adsorptive capacity of this membrane and its clinical implication, especially in comparisons of cardiovascular and atherosclerotic diseases that appear to be related to the concentrations of these metabolites, practically impossible to remove with standard membranes.

Expanded Haemodialysis Therapy of Chronic Haemodialysis Patients Prevents Calcification and Apoptosis of Vascular Smooth Muscle Cells in vitro

Background: Vascular calcification is a common phenomenon in patients with chronic kidney disease and strongly associated with increased cardiovascular mortality. Vascular calcification is an active process mediated in part by inflammatory processes in vascular smooth muscle cells (VSMC). These could be modified by the insufficient removal of proinflammatory cytokines through conventional high-flux (HF) membranes. Recent trials demonstrated a reduction of inflammation in VSMC by use of dialysis membranes with a higher and steeper cut-off. These membranes caused significant albumin loss. Therefore, the effect of high retention Onset (HRO) dialysis membranes on vascular calcification and its implications in vitro was evaluated. Methods: In the PERCI II trial, 48 chronic dialysis patients were dialyzed using HF and HRO dialyzers and serum samples were collected. Calcifying VSMC were incubated with the serum samples. Calcification was determined using alizarin red staining (AZR) and determination of alkaline phosphatase (ALP) activity. Furthermore, apoptosis was evaluated, and release of matrix Gla protein (MGP), osteopontin (OPN) and growth differentiation factor 15 (GDF-15) were measured in cell supernatants. Results: Vascular calcification in vitro was significantly reduced by 24% (ALP) and 36% (AZR) after 4 weeks of HRO dialysis and by 33% (ALP) and 48% (AZR) after 12 weeks of dialysis using HRO membranes compared to HF dialysis. Apoptosis was significantly lower in the HRO group. The concentrations of MGP and OPN were significantly elevated after incubation with HF serum compared to HRO serum and healthy controls. Similarly, GDF-15 release in the supernatant was elevated after incubation with HF serum, an effect significantly ameliorated after treatment with HRO medium. Conclusions: Expanded haemodialysis therapy reduces the pro-calcific potential of serum from dialysis patients in vitro. With a markedly reduced albumin filtration compared to high cut-off dialysis, use of the HRO dialyzers may possibly provide a treatment option for chronic dialysis patients to reduce the progression of vascular calcification.

Effect of High-Cutoff Hemodialysis vs Conventional Hemodialysis on Hemodialysis Independence Among Patients With Myeloma Cast Nephropathy

Cast nephropathy is the main cause of acute kidney injury in multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Strategies to rapidly remove nephrotoxic serum-free light chains combined with novel antimyeloma agents have not been evaluated prospectively. To compare the hemodialysis independence rate among patients newly diagnosed with myeloma cast nephropathy treated with hemodialysis using a high-cutoff dialyzer (with very large membrane pores and high permeability to immunoglobulin light chains) or a conventional high-flux dialyzer (with small pores and lower permeability). Randomized clinical trial involving 98 patients with biopsy-proven myeloma cast nephropathy requiring hemodialysis treated at 48 French centers between July 2011 and June 2016; the final date of follow-up was June 29, 2016. Intensive hemodialysis (eight 5-hour sessions over 10 days) with either a high-cutoff dialyzer (46 patients) or a conventional high-flux dialyzer (48 patients). All patients received the same chemotherapy regimen of bortezomib and dexamethasone. Primary end point was hemodialysis independence at 3 months; secondary end points: hemodialysis independence rates at 6 and 12 months, hemodialysis- and chemotherapy-related adverse events, and death. Among 98 randomized patients, 94 (96%) (median age, 68.8 years [interquartile range, 61.2-75.3 years]; 45% women) were included in the modified intent-to-treat analysis. The hemodialysis independence rate at 3 months was 41.3% (n = 19) in the high-cutoff hemodialysis group vs 33.3% (n = 16) in the conventional hemodialysis group (between-group difference, 8.0% [95% CI, -12.0% to 27.9%], P = .42); at 6 months, the rate was 56.5% (n = 26) vs 35.4% (n = 17), respectively (between-group difference, 21.1% [95% CI, 0.9% to 41.3%], P = .04); and at 12 months, the rate was 60.9% (n = 28) vs 37.5% (n = 18) (between-group difference, 23.4% [95% CI, 3.2% to 43.5%], P = .02). The incidence of hemodialysis-related adverse events was 43% in the high-cutoff hemodialysis group vs 39% in the conventional hemodialysis group; chemotherapy-related serious adverse events, 39% vs 37%, respectively; and at 12 months, 9 patients vs 10 patients died. Among patients with myeloma cast nephropathy treated with a bortezomib-based chemotherapy regimen, the use of high-cutoff hemodialysis compared with conventional hemodialysis did not result in a statistically significant difference in hemodialysis independence at 3 months. However, the study may have been underpowered to identify an early clinically important difference. clinicaltrials.gov Identifier: NCT01208818.

The unresolved problem of beta-2 microglobulin amyloid deposits in the intervertebral discs of long-term dialysis patients

BackgroundDialysis-related destructive spondyloarthropathy caused by beta-2 microglobulin (β2M) amyloid deposits in intervertebral discs is a major burden for patients undergoing long-term dialysis. This study aimed to quantify the presence of β2M amyloid deposits in the intervertebral disc tissue of such patients and analyze whether there was a significant correlation between β2M accumulation and the duration of dialysis.MethodsTwo groups of patients who had undergone surgery for degenerative spinal pathologies were selected: the dialysis group (n = 29) with long-term dialysis and the control group (n = 10) with no renal impairment. Tissue sections were prepared from specimens of intervertebral disc tissue obtained during spinal surgery and analyzed via histological staining, including immunohistochemistry (IHC) and Congo red.ResultsThere was a statistically significant multifold increase of β2M expression in the disc tissue of long-term dialysis patients when compared to non-dialysis patients, as shown by both IHC (0.019 ± 0.023 μm2 vs. 0.00020 ± 0.00033 μm2, respectively; p = 0.012) and Congo red staining (0.027 ± 0.041 μm2 vs. 9.240 × 10−5 ± 5.261 × 10−5 μm2, respectively; p = 0.047). We also note a moderate strength positive correlation between the duration of dialysis and positive IHC (r = 0.39; p = 0.015) and Congo-red staining (r = 0.42; p = 0.007).ConclusionsThe problem of β2M amyloidosis in long-term dialysis patients remains unresolved even with predominant use of high-flux dialysis membranes. This highlights the insufficiency of current dialysis modalities to effectively filter β2M.

Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis modalities: a meta-analysis of published studies.

Recent meta-analyses suggest that higher removal of beta-2 microglobulin (β2M) with either high-flux (HFD) dialysis or hemodiafiltration (HDF) may be associated with decreased total and cardiovascular mortality in dialysis patients. However, there are limited data about the performance of high flux dialyzers and/or convective therapies in removing β2M. This is a random effects meta-analysis and meta-regression of data extracted from randomized controlled trials and observational studies in hemodialysis, hemofiltration and HDF regarding the efficiency of high flux dialyzers to remove β2M. Studies were searched using ProQuest in SCOPUS, EMBASE and MEDLINE. We included 69 studies from 1 January 2001 to 12 June 2017 on 1879 patients with 6771 available measurements. Average β2M clearance was 48.75 mL/min [95% confidence interval (CI) 42.50-55.21] for conventional HF dialysis, and 87.06 mL/min (95% CI 75.08-99.03) for convective therapies (hemofiltration and HDF) with substantial heterogeneity among studies [P (Q) ≤ 0.001]. In multivariable meta-regression analyses, we found significantly higher β2M clearance for polyarylethersulfone dialyzers when used for HFD and polysulfone membranes in convective therapies. However, the mass of β2M removed into the dialysate did not depend on membrane material. Adjusted dialysate-side (-22.279, 95% CI -9.8 to -34.757, P < 0.001) β2M clearances were significantly lower than whole blood clearances, suggesting that adsorption contributes substantially to β2M removal. Higher Kuf, blood flow and substitution fluid rates but not dialysate flow rates were associated with statistically significant and clinically meaningful elevation in β2M clearance from the body independent of the dialysis modality. Membrane composition and characteristics, modality (convective versus diffusive), blood flow rates and substitution fluid rates in HDF play a significant role in the efficient removal of β2M from the body in both diffusive and convective dialysis.

Precise Quantitative Assessment of the Clinical Performances of Two High-Flux Polysulfone Hemodialyzers in Hemodialysis: Validation of a Blood-Based Simple Kinetic Model Versus Direct Dialysis Quantification.

Highly permeable dialysis membranes with better design filters have contributed to improved solute removal and dialysis efficacy. However, solute membrane permeability needs to be well controlled to avoid increased loss of albumin that is considered to be detrimental for dialysis patients. A novel high-flux dialyzer type (FX CorDiax; Fresenius Medical Care) incorporating an advanced polysulfone membrane modified with nano-controlled spinning technology to enhance the elimination of a broader spectrum of uremic toxins has been released. The aim of this study was to compare in the clinical setting two dialyzer types having the same surface area, the current (FX dialyzer) and the new dialyzer generation (FX CorDiax), with respect to solute removal capacity over a broad spectrum of markers, including assessment of albumin loss based on a direct dialysis quantification method. We performed a crossover study following an A1-B-A2 design involving 10 patients. Phase A1 was 1 week of thrice-weekly bicarbonate hemodialysis with the FX dialyzer, 4 h per treatment; phase B was performed with a similar treatment regimen but with a new FX CorDiax dialyzer and finally the phase A2 was repeated with FX dialyzer as the former phase. Solute removal markers of interest were assessed from blood samples taken before and after treatment and from total spent dialysate collection (direct dialysis quantification) permitting a mass transfer calculation (mg/session into total spent dialysate/ultrafiltrate). On the blood side, there were no significant differences in the solute percent reduction between FX CorDiax 80 and FX 80. On the dialysate side, no difference was observed regarding eliminated mass of different solutes including β2 -microglobulin (143.1 ± 33.6 vs. 138.3 ± 41.9 mg, P = 0.8), while the solute mass removal of total protein (1.65 ± 0.51 vs. 2.14 ± 0.75 g, P = 0.04), and albumin (0.41 ± 0.21 vs. 1.22 ± 0.51 g, P < 0.001) were significantly less for FX CorDiax 80 compared to the FX 80 dialyzer. The results of this cross-over study indicate that the new FX CorDiax dialyzer has highly effective removal of middle molecules, without any concomitant increase in total protein and albumin loss. The clinical relevance and potential benefit of this finding needs to be determined.

Soluble transferrin receptor as a marker of erythropoiesis in patients undergoing high-flux hemodialysis.

Anemia is a common complication in chronic kidney disease (CKD) patients receiving hemodialysis. The effect of high-flux dialysis (HFD) on anemia remains unclear. This prospective study aimed to evaluate the effect of HFD on anemia, and the potential of soluble transferrin receptor (sTfR) as a marker of iron status and erythropoiesis in CKD patients on hemodialysis. Forty patients, who switched from conventional low-flux dialysis to HFD for 12 months, were enrolled in this study. The levels of sTfR, hemoglobin (Hb), iron, and nutritional markers, as well as the dose of recombinant human erythropoietin (rhEPO) and use of chalybeate were determined at 0, 2, 6, and 12 months after starting HFD. HFD significantly increased the hemoglobin level and reduced sTfR level in CKD patients (p < 0.05). In addition, significant decreasing linear trends were observed for rhEPO dosage and chalybeate use (p < 0.05). The level of sTfR was positively correlated with the percentage of reticulocytes (RET%), rhEPO dose, and chalybeate use, while it was negatively correlated with Hb levels and total iron-binding capacity results (all p < 0.05). A univariate generalized estimating equation (GEE) model showed that the Hb level, RET%, rhEPO dose, and chalybeate use were the variables associated with sTfR levels. A multivariate GEE model showed that the time points when hemodialysis was performed were the variables associated significantly with sTfR levels. Overall, our findings suggest that HFD can effectively improve renal anemia in hemodialysis patients, and sTfR could be used as a marker of erythropoiesis in HFD patients.

Comparative analysis of the long-term effect of two families of high-flux polysulfone dialysers on platelet count: a retrospective cross-sectional study.

IntroductionThrombocytopenia is a potential complication of hemodialysis (HD), and its occurrence has been described even with highly biocompatible polysulfone (PSf) membranes. Dialysis units routinely monitor platelet (PLT) count at the beginning of HD sessions. However, considering that the long-term effects on PLT count could easily be missed, the prevalence of HD-related thrombocytopenia could be underestimated. In the present study, we aimed to investigate the following: 1) the long-term impact of HD treatment on PLT count, comparing two families of dialysis membranes made up of similar PSfs; 2) whether the switch between the dialysis membranes studied significantly affects PLT count; and 3) the prevalence and the risk of HD-induced thrombocytopenia according to the dialysis membranes used.MethodsA cross-sectional retrospective study was performed comprising 157 adult chronic HD patients. The HD membranes under investigation were of the series FX, Helixone® Fresenius (Filters A), and Polyflux® Gambro (Filters B). Patients were treated in 4 dialysis units in Southern Switzerland. Data were collected from a centralized computing platform.FindingsPLT count significantly differs between Filters A and B with, respectively, 188 (153–243) ×10E9/L versus 214 (179–255) ×10E9/L (p=0.036). The prevalence of thrombocytopenia was higher for Filter A compared with Filter B (28.4% versus 12.8%; p<0.001). The switch from Filter A to Filter B significantly affected PLT count: from 189 (146–217) ×10E9/L to 217 (163–253) ×10E9/L (p<0.001; analysis on 26 patients). A linear random-intercept model confirmed the results (β coefficient =35.214; SE =5.956; p<0.001). In a mixed-effects logistic regression model, the risk of thrombocytopenia for Filter B was 0.157 (CI =0.056–0.442).DiscussionOur data suggest that among the PSf membranes studied, the FX membrane induced a lasting decrease in PLT count and caused significantly more thrombocytopenia. Prospective studies are warranted to verify our findings.

Proteomics Investigations into Serum Proteins Adsorbed by High-Flux and Low-Flux Dialysis Membranes.

Hemodialysis is one of the most important therapies for patients with uremia, and the dialysis membrane is the predominant factor that impacts the efficiency of dialysis. Here, a protein adsorption on two different membranes is investigated to provide a basis for improving dialysis materials. Two cases treated with the Polyflux 14L low-flux dialyzer and the Polyflux 140H high-flux dialyzers during two continuous therapies are selected. Four used dialyzers from selected patients are infused with C12Im-Cl to elute the adsorbed proteins. Then labeled digested proteins adsorb by Polyflux 140H and Polyflux 14L with 13 CD2 O and NaCNBD3 (light labeling, L) and CD2 O and NaCNBH3 (heavy labeling, H), respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to identify the proteins. According to the ratio (Light labeling/Heavy labeling), the eluted proteins are divided into three groups: significantly higher, significantly lower, and no significant differences with a ratio of >2, <0.5, and 0.5-2, respectively. A total of 668 proteins are identified by LC-MS/MS, among which 177 proteins are retained more by the Polyflux 140H membrane (ratio >2), 320 proteins are retained more by the Polyflux 14L membrane (ratio <0.5), and 171 proteins show no significant difference (ratio 0.5-2) between the two types of membranes. Statistical significance is shown in the percentage of adsorbed proteins with an isoelectric point (pI) ranging from 9 to 10 (19.08 versus 7.69%; χ2 = 11.87, p = 0.0006). Proteins with a molecular weight (MW) of 10-15 kDa tend to deposit on Polyflux 140H compared with Polyflux 14L (25 versus 9.23%; χ2 = 18.66, p = 0.0000) and proteins with a MW of 30-60 kDa tend to deposit on Polyflux 14L compared with Polyflux 140H (36.54 versus 22.37%; χ2 = 8.96, p = 0.0028). According to gene ontology analysis, the proteins adsorbed by dialysis membranes are closely related to activation of complement system and the coagulation cascade. The proteins adsorbed by Polyflux 140H and Polyflux 14L show significant differences in PI, MW, and protein class. Proteomic techniques are an effective approach for studying hemodialysis membranes.

Effect of dialyzer membrane materials on survival in chronic hemodialysis patients: Results from the annual survey of the Japanese Nationwide Dialysis Registry.

BackgroundLittle information is available regarding which type of dialyzer membrane results in good prognosis in patients on chronic hemodialysis. Therefore, we conducted a cohort study from a nationwide registry of hemodialysis patients in Japan to establish the association between different dialyzer membranes and mortality rates.MethodsWe followed 142,412 patients on maintenance hemodialysis (female, 39.1%; mean age, 64.8 ± 12.3 years; median dialysis duration, 7 [4–12] years) for a year from 2008 to 2009. We included patients treated with seven types of high-flux dialyzer membranes at baseline, including cellulose triacetate (CTA), ethylene vinyl alcohol (EVAL), polyacrylonitrile (PAN), polyester polymer alloy (PEPA), polyethersulfone (PES), polymethylmethacrylate (PMMA), and polysulfone (PS). Cox regression was used to estimate the association between baseline dialyzers and all-cause mortality as hazard ratios (HRs) and 95% confidence intervals for 1-year mortality adjusting for potential confounders, and propensity score matching analysis was performed.ResultsThe distribution of patients treated with each membrane was as follows: PS (56.0%), CTA (17.3%), PES (12.0%), PEPA (7.5%), PMMA (4.9%), PAN (1.2%), and EVAL (1.1%). When data were adjusted using basic factors, with PS as a reference group, the mortality rate was significantly higher in all groups except for the PES group. When data were further adjusted for dialysis-related factors, HRs were significantly higher for the CTA, EVAL, and PEPA groups. When the data were further adjusted for nutrition-and inflammation-related factors, HRs were significantly lower for the PMMA and PES groups compared with the PS group. After propensity score matching, HRs were significantly lower for the PMMA group than for the PS group.ConclusionThe results suggest that the use of different membrane types may affect mortality in hemodialysis patients. However, further long-term prospective studies are needed to clarify these findings, including whether the use of the PMMA membrane can improve prognosis.

Ultrapure dialysis water obtained with additional ultrafilter may reduce inflammation in patients on hemodialysis

BackgroundPatients on standard dialysis, in particular those on high-flux and high-efficiency dialysis, are exposed to hundreds of liters of dialysis-water per week. The quality of dialysis-water is a factor responsible for inflammation in dialysis patients. Inflammation is a potent trigger of atherosclerosis and a pathogenetic factor in anemia, increasing mortality and morbidity in dialysis patients. Current systems for water treatment do not completely eliminate bacteria and endotoxins. This prospective study tested whether improved dialysis-water purity by an additional ultrafilter can reduce inflammation and ameliorate hemoglobin levels, with a consequent reduction in erythropoietin-stimulating agents (ESA).MethodsAn ultrafilter, composed of two serially positioned devices with polysulfone membranes of 2.0 and 1.0 m2, respectively, was positioned within the fluid pathway before the dialysis machine. Prevalent dialysis patients were assigned either to continue dialysis with conventional dialysis-water (control phase) or to initiate dialysis sessions with improved dialysis-water purity (study phase). After 6 months, patients were crossed over. Total study duration was 1 year. Routine chemistry, bacterial count, endotoxin levels in dialysis-water as well as blood levels of pro- and anti-inflammatory cytokines, human serum amyloid A, C-reactive protein and fraction 5 of complement were measured.ResultsThirty-two patients completed the study. Mean bacterial count was lower and endotoxin levels were absent in dialysis-water obtained with the ultrafilter. At the end of the study-phase, C-reactive protein and pro-inflammatory cytokines decreased while anti-inflammatory ones increased. Hemoglobin levels were improved with lower ESA doses.ConclusionsAn additional ultrafilter improved dialysis-water purity, reduced levels of inflammation markers, ameliorated hemoglobin concentration with reduced ESA doses. These results remain speculative but they may generate studies to assess whether improved dialysis-water quality with an ultrafilter can reduce inflammation and improve survival of dialysis patients.