Predilution Hemodiafiltration Research Articles

Anticoagulation for people receiving long-term haemodialysis.

Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding. To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included. We searched the Cochrane Kidney and Transplant Register of Studies up to November 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating anticoagulant agents administered during HD treatment in adults and children with kidney failure. Two authors independently assessed the risk of bias using the Cochrane tool and extracted data. Treatment effects were estimated using random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE). We included 113 studies randomising 4535 participants. The risk of bias in each study was adjudicated as high or unclear for most risk domains. Compared to UFH, LMWH had uncertain effects on extracorporeal circuit thrombosis (3 studies, 91 participants: RR 1.58, 95% CI 0.46 to 5.42; I2 = 8%; low certainty evidence), while major bleeding and minor bleeding were not adequately reported. Regional citrate anticoagulation may lower the risk of minor bleeding compared to UFH (2 studies, 82 participants: RR 0.34, 95% CI 0.14 to 0.85; I2 = 0%; low certainty evidence). No studies reported data comparing regional citrate to UFH on risks of extracorporeal circuit thrombosis and major bleeding. The effects of very LMWH, danaparoid, prostacyclin, direct thrombin inhibitors, factor XI inhibitors or heparin-grafted membranes were uncertain due to insufficient data. The effects of different LMWH, different doses of LMWH, and the administration of LMWH anticoagulants using inlet versus outlet bloodline or bolus versus infusion were uncertain. Evidence to compare citrate to another citrate or control was scant. The effects of UFH compared to no anticoagulant therapy or different doses of UFH were uncertain. Death, dialysis vascular access outcomes, blood transfusions, measures of anticoagulation effect, and costs of interventions were rarely reported. No studies evaluated the effects of treatment on non-fatal myocardial infarction, non-fatal stroke and hospital admissions. Adverse events were inconsistently and rarely reported. Anticoagulant strategies, including UFH and LMWH, have uncertain comparative risks on extracorporeal circuit thrombosis, while major bleeding and minor bleeding were not adequately reported. Regional citrate may decrease minor bleeding, but the effects on major bleeding and extracorporeal circuit thrombosis were not reported. Evidence supporting clinical decision-making for different forms of anticoagulant strategies for HD is of low and very low certainty, as available studies have not been designed to measure treatment effects on important clinical outcomes.

Improved Quality of Life in Postdilution Compared to Predilution Hemodiafiltration in a European Cohort of Dialysis Patients

Improved Quality of Life in Postdilution Compared to Predilution Hemodiafiltration in a European Cohort of Dialysis Patients

Systematic Comparison of Uremic Toxin Removal Using Different Hemodialysis Modes: A Single-Center Crossover Prospective Observational Study

Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group. Twenty-six patients were treated by those three techniques of extra renal epuration. Mean Kt/Vurea was not different between the treatment methods. Mean reduction ratio of beta2microglobulin was significantly higher for both HDF treatments than for HD (p < 0.001). Myoglobin, kappa, and lambda free light chain reduction ratio was significantly different between the modes: 37.75 ± 11.95%, 45.31 ± 11% and 61.22 ± 10.56%/57.21 ± 12.5%, 63.53 ± 7.93%, and 68.40 ± 11.79%/29.12 ± 8.44%, 34.73 ± 9.01%, and 45.55 ± 12.31% HD, preHDF, and postHDF, respectively (p < 0.001). Mean protein-bound solutes reduction ratio was not different between the different treatments except for PCS with a higher reduction ratio during HDF treatments. Mean albumin loss was always less than 2 g. HDF improved removal of middle molecules but had no effect on indoles concentration without any difference between synthetic dialysis membranes.

What Is the Difference between Post- and Pre-Dilution in On-Line Haemodiafiltration in the Removing of Median-Molecular-Weight Toxins?

Introduction: β2-microglobulin and prolactin are medium-molecular-weight toxins. We believe that the rate of removal of these molecules, using filters with two different surfaces, in post- and pre-dilution haemodiafiltration, will be of interest to the literature. Methods: We studied, in 12 haemodialyzed patients, the removal of those, with filter with surface of 2.5 m2 (Group A) or 2.1 m2 (Group B) with post-dilution haemodiafiltration, and with a filter with surface 2.5 m2 with pre-dilution (Group C). Results: Satisfactory removal of β2-microglobulin (best with post-dilution) was found, and a good rate of removal of prolactin without the filter surface played a role in both cases. Conclusion: The elimination of β2-microglobulin in post-dilution is not affected by the filter surface area. Pre-dilution achieves removal of β2-microglobulin, less than that of post-dilution. Prolactin was removed satisfactorily regardless of the filter surface in post-dilution, and its removal appears to be less than that of β2-microglobulin.

Basic physics of hemodiafiltration.

Standard high-flux hemodialysis (HD) clears urea very efficiently but is less efficient at clearing uremic toxins with larger molecule size, which diffuse more slowly. Hemodiafiltration (HDF) provides much higher convection rates, thereby reliably increasing the clearance of these larger toxins. However, the high ultrafiltration volumes employed by HDF significantly increase the concentration of proteins and lipids in the dialyzer blood compartment. This has the effect of increasing plasma viscosity, which opposes solute diffusion, and increasing plasma oncotic pressure, which opposes convection. The negatively charged plasma proteins also influence the equilibration of ions between dialysate and blood compartments. These effects result in varying conditions for solute transport along the length of the dialyzer and along the radial distance from the membrane within the dialyzer fibers. High-flux dialyzers can be designed to augment solute diffusion and internal filtration, so that their performance approaches that of HDF. This avoids some of the mechanical complexity of HDF, but such enhanced dialyzers may be more difficult to manufacture, control and monitor. Here, we present and discuss the most important physical phenomena associated with HDF therapy, providing an overview of its main concepts and principles. In particular, we discuss the physics of solute diffusion and convection and the factors affecting them, and we compare predilution or postdilution HDF with enhanced HD.

Effects of predilution hemodiafiltration-induced intradialytic left ventricular systolic dysfunction compared to high-flux hemodialysis.

Hemodialysis (HD)-induced myocardial ischemia may lead to left ventricular (LV) dysfunction after normal perfusion returns. This study aimed to assess the short-term influence of predilution hemodiafiltration (HDF) and high-flux hemodialysis (HD) on intradialytic LV systolic function, and hematologic and biochemical risk factors. This cross-over clinical trial enrolled 38 dialysis patients who were randomized equally into one of two treatment sequences: 1-week predilution HDF treatment followed by 1-week high-flux HD, and vice versa. LV systolic function was assessed by echocardiography before and after the mid-week dialysis session. Hematologic and biochemical parameters were also measured. Replacement fluid volume for all patients was 24.2 ± 1.3 L/session. Subjects' mean age was 53.3 ± 11.8years and 24 were males. LV ejection fraction (LVEF) decreased from 61.31 ± 9.96 to 59.03 ± 10.37% after HDF (P = 0.016), and increased from 61.69 ± 11.08 to 62.72 ± 11.26% after high-flux HD (P = 0.190). Average of peak LV systolic tissue velocity increased from 6.74 ± 1.23 to 6.98 ± 1.56cm/s after HDF (P = 0.246), and increased from 6.71 ± 1.34 to 7.44 ± 2.18cm/s (P = 0.039) after high-flux HD. The ratio between peak LV early diastolic mitral inflow velocity and peak LV early diastolic tissue velocity (E/E') at the septal mitral annulus decreased to 18 ± 9 from 21 ± 11 (P = 0.147) after HDF, and to 17 ± 8 from 20 ± 8 (P = 0.037) after high-flux HD. β2-microglobulin was reduced more during HDF than during high-flux HD (70.7 ± 5.3 vs. 67.7 ± 3.9%, P < 0.001). Predilution HDF decreases intradialytic LV systolic function more than high-flux HD. Randomized controlled trials with a larger multi-center sample and long-term follow-up are required to demonstrate the potential mechanisms of predilution HDF effecting on ventricular function.

Effects of Japanese-style online hemodiafiltration on survival and cardiovascular events

BackgroundAll-cause mortality can be reduced in patients receiving European-style high-volume post-dilution online hemodiafiltration (post-OHDF) compared with hemodialysis (HD). Japanese-style high-volume pre-dilution online hemodiafiltration (pre-OHDF) can also decrease all-cause mortality. No studies have investigated survival in patients receiving Japanese-style post-OHDF, and directly compared survival between pre-OHDF and post-OHDF. This study sought to clarify these issues.MethodsWe conducted this retrospective observational study at multiple facilities of our medical corporation, which have similar quality of healthcare management, from July 1, 2017 to July 1, 2020. Japanese-style OHDF included pre-OHDF and post-OHDF. Pre-OHDF and post-OHDF were each divided into high-volume and low-volume subgroups. We compared 3-year all-cause mortality and cardiovascular events between OHDF and high-flux HD using propensity score matching. In addition, we examined the effects of different modalities through comparisons between high-volume and low-volume pre-OHDF and between pre-OHDF and post-OHDF.ResultsPost-OHDF was associated with significantly lower all-cause mortality (P = 0.004, log-rank test; hazard ratio [HR] 0.257, 95% confidence interval [CI] 0.094–0.701) and cardiovascular events during all 3 years (P < 0.05) compared with HD. High-volume post-OHDF was associated with lower all-cause mortality compared with hemodialysis (log-rank test P = 0.022) but low-volume post-OHDF was not. Pre-OHDF was also associated with lower all-cause mortality (P < 0.001, log-rank test; HR 0.316; 95% CI 0.212–0.472) compared with HD but was not associated with cardiovascular events. All-cause mortality did not significantly differ between post-OHDF and pre-OHDF.ConclusionsThese findings suggest that Japanese-style post-OHDF may improve all-cause mortality to a level similar to that of pre-OHDF and that post-OHDF, particularly high-volume post-OHDF may reduce cardiovascular events.

Mixed- versus predilution hemodiafiltration effects on convection volume and small and middle molecule clearance in hemodialysis patients: a prospective randomized controlled trial.

BackgroundThe use of newly developed mixed-dilution hemodiafiltration (HDF) can supplement the weaknesses of pre- and postdilution HDF. However, it is unclear whether mixed-HDF performs well compared to predilution HDF.MethodsWe conducted a prospective, open-labeled, randomized controlled trial from two hemodialysis centers in Korea. Between January 2017 and September 2019, 60 patients who underwent chronic hemodialysis were randomly assigned at a 1:1 ratio to receive either predilution HDF (n = 30) or mixed-HDF (n = 30) for 6 months. We compared convection volume, changes in small- and medium-sized molecule clearance, high-sensitive C-reactive protein (hs-CRP) level, and dialysis-related parameters between the two dialysis modalities.ResultsA mean effective convection volume of 41.0 ± 10.3 L/session in the predilution HDF group and 51.5 ± 9.0 L/session in the mixed-HDF group was obtained by averaging values of three time-points. The difference in effective convection volume between the groups was 10.5 ± 1.3 L/session. This met the preset noninferiority criteria, suggesting that mixed-HDF was noninferior to predilution HDF. Moreover, the β2-microglobulin reduction rate was greater in the mixed-HDF group than in the predilution HDF group, while mixed-HDF provided greater transmembrane pressure. There were no significant between-group differences in Kt/V urea levels, changes in predialysis hs-CRP levels, proportions of overhydration, or blood pressure values. Symptomatic intradialytic hypotension episodes and other adverse events occurred similarly in the two groups.ConclusionUse of mixed-HDF was comparable to predilution HDF in terms of delivered convection volume and clinical parameters. Moreover, mixed-HDF provided better β2-microglobulin clearance than predilution HDF.

How biocompatible haemodialysers can conquer the need for systemic anticoagulation even in post-dilution haemodiafiltration: a cross-over study.

BackgroundWhile systemic anticoagulation is most widely used in haemodialysis (HD), contraindications to its use might occur in particular settings. The Solacea™ haemodialyser with an asymmetric triacetate membrane claims improved biocompatibility and has already shown promising results when used in combination with only half dose of anticoagulation. To quantify the performance of the Solacea™ when further decreasing anticoagulation to zero, fibre blocking was assessed by micro-computed tomography (micro-CT).MethodsTen maintenance HD patients underwent six dialysis sessions at midweek using a Solacea™ 19H dialyser, consecutively in pre-dilution haemodiafiltration (pre-HDF), HD and post-dilution HDF (post-HDF). After the first three sessions with only a quarter of their regular anticoagulation dose (one-quarter), the last three sessions were performed without anticoagulation (zero). Dialyser fibre blocking was quantified in the dialyser outlet potting using a 3D micro-CT scanning technique post-dialysis.ResultsEven in case of reduced (one-quarter) anticoagulation, the relative number of open fibres post-dialysis was almost optimal, i.e. 0.96 (0.87–0.99) with pre-HDF, 0.99 (0.97–0.99) with HD and 0.97 (0.92–0.99) with post-HDF. Fibre patency was mildly decreased for pre-HDF and HD when anticoagulation was decreased from one-quarter to zero, i.e. to 0.76 (0.61–0.85) with pre-HDF (P = 0.004) and to 0.80 (0.77–0.89) with HD (P = 0.013). Comparing the results for zero anticoagulation, post-HDF [i.e. 0.94 (0.82–0.97)] performed as well as HD and pre-HDF.ConclusionsThe Solacea™ dialyser provides promising results for use in conditions where systemic anticoagulation is contraindicated. Post-HDF, although inducing haemoconcentration in the dialyser, is equally effective for fibre patency in case of zero anticoagulation as pre-HDF and HD when using Solacea™.

Strategies for asymmetrical triacetate dialyser heparin-free effective haemodialysis: the SAFE study.

BackgroundIn haemodialysis, maintaining patency of the extracorporeal circuit requires the use of anticoagulants. Although (low molecular weight) heparins are the mainstay, these are not well tolerated in all patients. Alternative approaches include saline infusion, citrate-containing dialysate, regional citrate anticoagulation or the use of heparin-coated membranes. Asymmetric cellulose triacetate (ATA) dialysers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialysers. The aim of this study was to test the clotting propensity of ATA when used without systemic anticoagulation.MethodsWe performed a Phase II pilot study in maintenance dialysis patients. The ‘Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis’ (SAFE) study was a two-arm open-label crossover study. In Arm A, patients were dialysed using 1.9 m2 ATA membranes in combination with a citrate-containing dialysate (1 mM). In Arm B, the ATA membrane was combined with high-volume predilution haemodiafiltration (HDF) without any other anticoagulation. The primary endpoint was the success rate to complete 4 h of haemodialysis without preterm clotting. Secondary endpoints included time to clotting and measures of dialysis adequacy.ResultsWe scheduled 240 dialysis sessions (120/arm) in 20 patients. Patients were randomized 1:1 to start with Arm A or B. All patients crossed to the other arm halfway through the study. A total of 232 (96.7%) study treatments were delivered. Overall, 23 clotting events occurred, 7 in Arm A and 16 in Arm B. The success rate in Arm A (ATA + citrate-containing dialysate) was 90.8/94.0% [intention to treat (ITT)/as treated]. The success rate in Arm B (ATA + predilution HDF) was 83.3/86.2% (ITT/as treated). Time to clotting was borderline significantly better in Arm A (Mantel-Cox log rank P = 0.05).ConclusionATA dialysers have a low clotting propensity and both predilution HDF and a citrate-containing dialysate resulted in high rates of completed dialysis sessions.

P1064HEPARIN-FREE DIALYSIS: A PHASE II PILOT STUDY USING ASYMMETRIC TRIACETATE (ATA) CELLULOSE DIALYZERS

Abstract Background and Aims Not all dialysis patients tolerate heparin anticoagulation. Heparin should be avoided in patients at high risk of bleeding. Strategies include saline infusion, citrate-containing dialysate, regional citrate anticoagulation and heparin-coated membranes. We recently studied the combination of a heparin-coated membrane and citrate-containing dialysate, with a success rate of 94% . Although this combination resulted in low rates of clotting, heparin-coated membranes are not ubiquitously available. The quest for easy to perform, safe and affordable heparin-free dialysis is on. Asymmetric cellulose triacetate (ATA) dialyzers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialyzers. Method We performed a phase II pilot study in maintenance dialysis patients. The ‘Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis (SAFE study)’ was a two-arm open-label cross-over study. In Arm 1, patients were dialyzed using a 1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan) in combination with citrate (1 mM) containing dialysate. In Arm 2, patients were dialyzed with the same 1.9 m2 ATA membrane, in combination with high volume predilution hemodiafiltration. The primary endpoint was the success rate to complete 4 hours of hemodialysis without preterm clotting. Results We scheduled 240 dialysis sessions (120 per arm) in twenty patients. Ten patients were randomized to start in Arm 1, the others to Arm 2. All patients crossed to the other arm halfway the study. 232 (96.7%) study treatments were delivered. Overall, 23 clotting events occurred, 7 in Arm 1 and 16 in Arm 2. Success rate in Arm 1 (ATA + citrate containing dialysate) was 90.8 / 94.0 % (intention to treat/ as treated). Success rate in Arm 2 (ATA + predilution HDF) was 83.3 / 86.2 % (intention to treat/ as treated). Therapy survival was borderline significantly better in Arm 1(Mantel-Cox log rank P = 0.05). Conclusion Asymmetric cellulose triacetate (ATA) dialyzers have a low clotting propensity. In combination with citrate-containing dialysate, asymmetric cellulose triacetate (ATA) may be a suitable alternative to heparin-coated membranes for systemic heparin-free hemodialysis.

P1100IMPACT OF THE RELATIONSHIP BETWEEN LOW MOLECULAR WEIGHT PROTEINS REMOVAL EFFICIENCIES AND THE VOLUME OF ALBUMIN LEAKAGE IN HEMODIAFILTRATION THERAPY

Abstract Background and Aims The purpose of hemodiafiltration (HDF) is to remove small- to large molecular weight solutes in order to prevent and treat complications and to improve the prognosis of dialysis patients. Especially, larger low molecular weight proteins (LMWPs) must be removed efficiently. β2-microglobulin (MG) (molecular weight [MW], 11.8 kDa: Stokes radius, 15.6A), is considered as an important marker of dialysis efficiency. However, MW of β2-MG is too small as a marker in HDF. Conversely, α1-MG (MW, 33 kDa: Stokes radius, 28.4A) is the most appropriate marker for evaluation of solute removal efficiency of HDF because of the following reasons: (1) optical molecular size; (2) not very low physiological blood concentration; (3) stable production rate; (4) removal by convection; and (5) accumulation in ESRD. Efficient removal of α1-MG without losing albumin (Alb) (MW,66 kDa: Stokes radius, 35.5A) is impossible even by HDF. In this study, we investigated the relationship between LMWP removal efficiencies and the volume of Alb leakage by analyzing the results of patients undergoing HDF. And we also evaluated the trend of the serum levels of patients who had received high-efficiency HDF for more than three years Method Eighty-seven patients who had received HDF in 2018–2019 were included. The results of HDF (a total of 435 sessions) were analyzed (blood flow rate, 261.5±28.5 mL/min; replacement fluid volume, 48.7 L/s pre-dilution on-line HDF and 14.2 L/s post-dilution on-line HDF). The removal efficiencies of β2-MG, prolactin (PRL), and α1-MG, and the volume of Alb leakage were examined. In addition, the relationship between the removal efficiency of each solute and the volume of Alb leakage was investigated. Changes in serum Alb level were analyzed in 13 patients who continued to receive high-efficiency HDF (the removal rate of α1-MG was 30% or more) for more than three years. Results Analysis of the results (mean ± SD) obtained from a total of 435 sessions (87 patients) showed that the removal rates of β2-MG, PRL, and α1-MG were 80.7 ± 4.5%, 75.8±9.4 and 33.8 ± 9.4%, respectively, and the Alb leakage was 3.9 ± 1.8 g/s. The equations of the approximate curve between Alb leakage and β2-MG, PRL, and α1-MG removal rates were expressed as follows: ï½™= 1.4197ln(x) + 78.972 (R2 = 0.0426), y = 9.7185ln(x) + 64.134 (R2 =0.4632), and ï½™™= 11.225ln(x) + 20.282 (R2 = 0.6191), respectively. These results indicate that the dynamics between Alb leakage and α1-MG removal are very similar. That is, although the molecular weight of Alb is twice as that of α1-MG, the difference in their Stokes radius is 20%; therefore, separate removal of Alb and α1-MG is impossible. The mean serum Alb level in 13 patients who received high-efficiency HDF for 3 years or longer was 3.59 ± 0.23 g/dL in January 2017 and 3.69 ± 0.28 g/dL in December 2019, revealing no changes. Conclusion The efficient removal of larger LMWPs leads to the leakage of Alb. However, an Alb leakage of 3 to 6 g/s has little influence on the serum Alb level of patients. Thus, α1-MG is the most appropriate marker of the solute removal efficiency of HDF.

Amino acid losses are lower during pre-dilution on-line HDF than HD of the same Kt/V for urea.

In this study, we investigated differences in amino acid losses between HD and pre-dilution on-line HDF with equal Kt/V for urea to determine which modality removes less amino acids from extravascular pools and ensures better nutrition. The subjects were patients receiving pre-dilution on-line HDF (n = 10) or HD (n = 10) at this hospital. Dialysis time was 4h for all patients. In patients on HD, the blood flow rate was 200mL/min and the dialysate flow rate was 463 ± 29.3mL/min. In patients on pre-dilution on-line HDF, the blood flow rate was 240 ± 20mL/min, the dialysate flow rate was 565.0 ± 42.5mL/min, and the substitution flow rate (substitution volume) was 252.8 ± 26.4mL/min (57.0 ± 6.0L). Kt/V for urea was comparable between patients on HD and patients on pre-dilution on-line HDF (1.46 ± 0.25 vs. 1.46 ± 0.31). Amino acid loss and clear space were evaluated. Patients on pre-dilution on-line HDF lost significantly less glutamine and arginine (p < 0.01 and p = 0.032) and significantly less nonessential amino acids (NEAAs) than patients on HD (p = 0.013). They also had significantly lower clear space of total amino acids (TAAs), NEAAs, essential amino acids (EAAs), and branched-chain amino acids (BCAAs) than patients on HD (Total AA p = 0.019, NEAA p = 0.018, EAA p = 0.024, BCAA p = 0.042). When Kt/V for urea is equal, pre-dilution on-line HDF ensures better nutrition than does HD.

Enhancement of solute clearance using pulsatile push-pull dialysate flow for the Quanta SC+: A novel clinic-to-home haemodialysis system.

The SC+ haemodialysis system developed by Quanta Dialysis Technologies is a small, easy-to-use dialysis system designed to improve patient access to self-care and home haemodialysis. A prototype variant of the standard SC+ device with a modified fluidic management system generating a pulsatile push-pull dialysate flow through the dialyser during use has been developed for evaluation. It was hypothesized that, as a consequence of the pulsatile push-pull flow through the dialyser, the boundary layers at the membrane surface would be disrupted, thereby enhancing solute transport across the membrane, modifying protein fouling and maintaining the surface area available for mass and fluid transport throughout the whole treatment, leading to solute transport (clearance) enhancement compared to normal haemodialysis (HD) operation. The pumping action of the SC+ system was modified by altering the sequence and timings of the valves and pumps associated with the flow balancing chambers that push and pull dialysis fluid to and from the dialyser. Using this unique prototype device, solute clearance performance was assessed across a range of molecular weights in two related series of laboratory bench studies. The first measured dialysis fluid moving across the dialyser membrane using ultrasonic flowmeters to establish the validity of the approach; solute clearance was subsequently measured using fluorescently tagged dextran molecules as surrogates for uraemic toxins. The second study used human blood doped with uraemic toxins collected from the spent dialysate of dialysis patients to quantify solute transport. In both, the performance of the SC+ prototype was assessed alongside reference devices operating in HD and pre-dilution haemodiafiltration (HDF) modes. Initial testing with fluorescein-tagged dextran molecules (0.3 kDa, 4 kDa, 10 kDa and 20 kDa) established the validity of the experimental pulsatile push-pull operation in the SC+ system to enhance clearance and demonstrated a 10 to 15% improvement above the current HD mode used in clinic today. The magnitude of the observed enhancement compared favourably with that achieved using pre-dilution HDF with a substitution fluid flow rate of 60 mL/min (equivalent to a substitution volume of 14.4 L in a 4-hour session) with the same dialyser and marker molecules. Additional testing using human blood indicated a comparable performance to pre-dilution HDF; however, in contrast with HDF, which demonstrated a gradual decrease in solute removal, the clearance values using the pulsatile push-pull method on the SC+ system were maintained over the entire duration of treatment. Overall albumin losses were not different. Results obtained using an experimental pulsatile push-pull dialysis flow configuration with an aqueous blood analogue and human blood ex vivo demonstrate an enhancement of solute transport across the dialyser membrane. The level of enhancement makes this approach comparable with that achieved using pre-dilution HDF with a substitution fluid flow rate of 60 mL/min (equivalent to a substitution volume of 14.4 L in a 4-hour session). The observed enhancement of solute transport is attributed to the disruption of the boundary layers at the fluid-membrane interface which, when used with blood, minimizes protein fouling and maintains the surface area.

Hemodialysis without anticoagulation: Less clotting in conventional hemodialysis than in predilution hemodiafiltration.

Hemodialysis patients with contraindication to systemic anticoagulation require a heparin-free hemodialysis technique. Among several alternatives to heparin, predilution hemodiafiltration (HDF) is often used, albeit without any confirmation of its effectiveness. Patients hospitalized in a nephrology ICU and hemodialysed for stage 5 CKD or AKI and with contraindication to systemic anticoagulation were randomized to either standard HD with a polysulfone membrane, or to predilution HDF with the same membrane. Coagulation activation was evaluated clinically by the need for premature termination and by the measurement of D-dimers. Two hundred dialysis sessions were performed in 155 patients. Survival curves showed better circuit survival in HD (P = 0.046). In HD, 12% of sessions were interrupted for coagulation versus 23% in predilution HDF (P = 0.04). Predilution HDF was associated with more premature clotting than conventional HD without improvement in dialysis duration or performance epuration indices. When aiming for a 4-hour duration session, conventional heparin-free hemodialysis can be safely proposed in most patients with high bleeding risk.

MON-114 COMPARISON OF ON-LINE HEMODIAFILTRATION AND HEMODIALYSIS ON THE REMOVAL RATE OF DRUGS

Recent data suggest that the removal rate of drugs is higher in predilution on-line hemodiafiltration(HDF) treatment because of the result in temporary reduction of serum protein binding rate. However, as far as searching, there are few studies comparing drug removal rates for Online-HDF and conventional hemodialysis therapy (HD). In this study, we compared the removal rate of drugs between in predilution on-line HDF and HD treatment.

MON-125 Release of uremic retention solutes from protein binding by hypertonic predilution hemodiafiltration: a novel therapeutic approach

Protein-bound uremic retention solutes accumulate in patients suffering from chronic kidney disease and its removal by hemodialysis is hampered. Therefore, we developed a dialysis technique where the protein-bound uremic retention solutes are removed more efficiently under high ionic strength. Protein-bound uremic solutes such as phenylacetic acid, indoxyl sulfate and p-cresyl sulfate was combined with plasma in the presence of increased ionic strength. The protein integrity of proteins and enzymatic activities were analysed. In-vitro dialysis of albumin solution was performed to investigate the clearance of the bound uremic retention solutes. In-vitro hemodiafiltrations of human blood were performed to investigate the influence of increased ionic strength on blood cell survival. The protein-bound fraction of phenylacetic acid, indoxyl sulfate and p-cresyl sulfate was significantly decreased from 59.4±3.4%, 95.7±0.6%, 96.9±1.5% to 36.4±3.7%, 87.8±0.6% and 90.8±1.3% respectively. The percentage of phenylacetic acid, indoxyl sulfate and p-cresyl sulfate released from protein was 23.0±5.7%, 7.9±1.1% and 6.1±0.2%. The clearance during in-vitro dialysis was increased by 13.1±3.6 %, 68.8±15.1 % and 53.6±10.2 % respectively. There was no difference in NaCl concentrations at the outlet of the dialyser using isotonic and hypertonic solutions In conclusion, this study forms the basis for establishing a novel therapeutic approach to remove the protein-bound retention solutes.

In silico comparison of protein-bound uremic toxin removal by hemodialysis, hemodiafiltration, membrane adsorption, and binding competition

Protein-bound uremic toxins (PBUTs) are poorly removed during hemodialysis (HD) due to their low free (dialyzable) plasma concentration. We compared PBUT removal between HD, hemodiafiltration (HDF), membrane adsorption, and PBUT displacement in HD. The latter involves infusing a binding competitor pre-dialyzer, which competes with PBUTs for their albumin binding sites and increases their free fraction. We used a mathematical model of PBUT/displacer kinetics in dialysis comprising a three-compartment patient model, an arterial/venous tube segment model, and a dialyzer model. Compared to HD, improvements in removal of prototypical PBUTs indoxyl sulfate (initial concentration 100 µM, 7% free) and p-cresyl sulfate (150 µM, 5% free) were: 5.5% and 6.4%, respectively, for pre-dilution HDF with 20 L replacement fluid; 8.1% and 9.1% for post-dilution HDF 20 L; 15.6% and 18.3% for pre-dilution HDF 60 L; 19.4% and 22.2% for complete membrane adsorption; 35.0% and 41.9% for displacement with tryptophan (2000 mg in 500 mL saline); 26.7% and 32.4% for displacement with ibuprofen (800 mg in 200 mL saline). Prolonged (one-month) use of tryptophan reduces the IS and pCS time-averaged concentration by 28.1% and 29.9%, respectively, compared to conventional HD. We conclude that competitive binding can be a pragmatic approach for improving PBUT removal.

Differences in Amino Acid Loss Between High-Efficiency Hemodialysis and Postdilution and Predilution Hemodiafiltration Using High Convection Volume Exchange—A New Metabolic Scenario? A Pilot Study

The objective of the study was to quantify the loss of total amino acids (TAAs), nonessential amino acids, essential amino acids, and branched chain amino acids (BCAAs) produced by high-efficiency hemodialysis (HEHD), postdilution hemodiafiltration (HDFpost), and predilution hemodiafiltration (HDFpre) using high ultrafiltration volumes; and to define the specific AA losses registered in HEHD, HDFpost, and HDFpre; to identify a potential metabolic and nutritional decline into protein energy wasting; to compare AA analysis of arterial blood samples taken from healthy controls and patients with end-stage renal disease undergoing hemodialysis. Identical dialysis monitors, membranes, and dialysate/infusate were used to homogenize extracorporeal body influence. Ten patients were recruited and randomized to receive treatment with HEHD, HDFpost, and HDFpre it was used on-line dialytic water methodologies (OL); patients' AA arterial concentrations were measured at the start and on completion of dialysis; TAA from the dialyzer filter was calculated, and baseline levels were subsequently compared with findings obtained 1year later. Finally, the results obtained were compared with the data from a study of 8 healthy volunteers conducted using bioimpedance analysis and laboratory blood tests to assess nutritional status. A higher convective dose results in a higher weekly loss of TAA, nonessential AAs, essential AAs, and BCAAs (HEHD: 15.7g; HDFpost-OL: 16.1g; HDFpre-OL: 16.3g, P<.01). After 12months, the same hemodialys patients showed a reduced body and water intracellular mass and reduced phase angle. Arterial concentrations of TAAs and BCAAs were lower than those detected in healthy subjects (P<.01). The study shows that the AA losses in dialytic liquid are greater after high exchange volume HDF techniques, especially HDFpre. The AA losses are not metabolically compensated, so these increase the derangements of predialytic arterial plasma AA levels. Both AA losses and arterial AA perturbations further worsened body composition already after 12months of additional dialysis.

Current approaches to middle molecule removal: room for innovation.

Aggressive removal of middle molecules or larger low-molecular-weight proteins (LMWPs) has been a growing concern following studies on their harmful effects on the mortality and morbidity of chronic dialysis patients. To remove larger LMWPs and some protein-bound uremic toxins (PBUTs), high- and medium-cutoff (HCOs and MCOs, respectively) membranes, convective therapy and protein adsorptive membranes are available. When we use HCO or MCO membranes for convective therapy, we have to take care to avoid massive albumin leakage during a dialysis session. Convection volume is an important element to increase middle molecule removal; however, a larger convection volume has a risk of larger leakage of albumin. Predilution hemodiafiltration is a useful measurement to increase larger LMWPs without massive albumin leakage. β2-microglobulin (B2M), α1-microglobulin (A1M) and albumin leakage during a dialysis session are useful parameters for assessing middle-molecule removal. Reduction ratios of B2M >80% and of A1M >35% are favorable to improve severe dialysis-related symptoms. The efficacy of middle molecule removal should be evaluated in comparison with clinical outcomes, mortality, morbidity and the improvement of dialysis-related symptoms. Recently some dialysis-related symptoms such as sleep disturbance, skin itchiness and dialysis hypotension have been recognized as good surrogate makers for mortality. Further studies to evaluate the relationship between middle molecule or PBUTs removal and the improvement of patient symptoms should be performed in well-designed randomized controlled trials.