Conventional High-flux Hemodialysis Research Articles

Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

Expanded Dialysis With Theranova Compared to Conventional High-Flux Hemodialysis: A Randomized Prospective 12-Month Study

Expanded Dialysis With Theranova Compared to Conventional High-Flux Hemodialysis: A Randomized Prospective 12-Month Study

Poređenje efikasnosti uklanjanja uremijskih toksina srednje molekulske mase između visokopropusne hemodijalize i postdilucione online hemodijafiltracije

Introduction. Conventional high-flux hemodialysis effectively removes uremic toxins of medium molecular weight of 0.5-15 (20) kDa, while postdilution online hemodiafiltration effectively removes uremic toxins of medium molecular weight in the range of 0.5-60 kDa. AIM. The aim of the study was to compare the efficacy of b2-microglobulin removal from the patient serum during a single session of conventional high-flux hemodialysis and postdilution online hemodiafiltration. METHOD. Eighty-five patients treated with conventional high-flux hemodialysis and thirty patients treated with postdilution online hemodiafiltration were examined. The main parameter for assessing the removal efficiency of medium molecular weight uremic toxins was serum b2microglobulin concentration before and after a single session of conventional high-flux hemodialysis and postdilution online hemodiafiltration. The following were used for statistical analysis: Kolmogorov-Smirnov test, Student's T test and Mann-Whitney U test. RESULTS. In patients treated with postdilution online hemodiafiltration, the average total convective volume was 21.38 ± 2.97 liters per session. The b2-microglobulin reduction index for the FX CorDiax 600 dialysis membrane was 61.76 ± 7.32%, while for the FX CorDiax 800 dialysis membrane it was 74.69 ± 6.51%. The albumin reduction index for the FX CorDiax 600 membrane was 3.48 ± 1.28%, and for the FX CorDiax 800 dialysis membrane it was 6.01 ± 2.97%. There is a highly statistically significant difference between the reduction index of b2-microglobulin and albumin, for two different dialysis modalities and two different dialysis membranes (p < 0.01). CONCLUSION. Postdilution online hemodiafiltration is more efficient in removing b2-microglobulin from patient serum, compared to conventional high-flux hemodialysis. Albumin loss during a single session of high-flux hemodialysis is lower compared to a single session of postdilution online hemodiafiltration. With both dialysis modalities, albumin loss is less than 4.0 g/4h. High-flux hemodialysis effectively prevents the development of dialysis-related amyloidosis, while postdilution online hemodiafiltration effectively prevents not only the development of dialysis-related amyloidosis, but also the development of resistance to erythropoietin and atherosclerotic cardiovascular diseases in the population treated with regular dialysis.

Predicting Residual Function in Hemodialysis and Hemodiafiltration—A Population Kinetic, Decision Analytic Approach

In this study, we introduce a novel framework for the estimation of residual renal function (RRF), based on the population compartmental kinetic behavior of beta 2 microglobulin (B2M) and its dialytic removal. Using this model, we simulated a large cohort of patients with various levels of RRF receiving either conventional high-flux hemodialysis or on-line hemodiafiltration. These simulations were used to estimate a novel population kinetic (PK) equation for RRF (PK-RRF) that was validated in an external public dataset of real patients. We assessed the performance of the resulting equation(s) against their ability to estimate urea clearance using cross-validation. Our equations were derived entirely from computer simulations and advanced statistical modeling and had extremely high discrimination (Area Under the Curve, AUC 0.888–0.909) when applied to a human dataset of measurements of RRF. A clearance-based equation that utilized predialysis and postdialysis B2M measurements, patient weight, treatment duration and ultrafiltration had higher discrimination than an equation previously derived in humans. Furthermore, the derived equations appeared to have higher clinical usefulness as assessed by Decision Curve Analysis, potentially supporting decisions for individualizing dialysis prescriptions in patients with preserved RRF.

Regulatory Considerations for Hemodiafiltration in the United States.

Online hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis. However, online hemodiafiltration is used sparsely in the United States in part because of a paucity of delivery systems cleared for clinical use by the US Food and Drug Administration. Although a pathway for regulatory approval exists in the United States, concerns remain, particularly regarding online production of the large volumes of sterile, nonpyrogenic substitution fluid infused directly into the bloodstream to maintain fluid balance. Clearly defined testing protocols, acceptable to Food and Drug Administration, will be useful to show that an online hemodiafiltration system is capable of routinely achieving a sterility assurance level of 10-6 and nonpyrogenic levels of endotoxin. Large-scale clinical experience has shown that systems providing this level of performance when combined with certain design features, such as redundancy, and an appropriate quality management process can routinely and safely produce substitution fluid for online hemodiafiltration.

Hemodiafiltration to Address Unmet Medical Needs ESKD Patients.

Hemodiafiltration combines diffusive and convective solute removal in a single therapy by ultrafiltering 20% or more of the blood volume processed using a high-flux hemodialyzer and maintaining fluid balance by infusing sterile nonpyrogenic replacement fluid directly into the patient's blood. In online hemodiafiltration, the large volumes of replacement fluid required are obtained by online filtration of standard dialysate through a series of bacteria- and endotoxin-retaining filters. Currently available systems for online hemodiafiltration are on the basis of conventional dialysis machines with added features to safely prepare and infuse replacement fluid and closely control fluid balance. Hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis, and recently completed randomized, controlled clinical trials suggest better patient survival with online hemodiafiltration compared with standard high-flux hemodialysis when a high convection volume is delivered. Hemodiafiltration is also associated with improvements in other clinical outcomes, such as a reduction in intradialytic hypotension, and it is now used routinely to treat >100,000 patients, mainly in Europe and Japan.

Influence of high-flux hemodialysis and hemodiafiltration on serum C-terminal agrin fragment levels in end-stage renal disease patients

C-terminal agrin fragment (CAF, 22kDa) has been shown to be a promising new rapid biomarker for kidney function. This study evaluated the influence of hemodialysis (HD) and hemodiafiltration (HDF) treatment on serum CAF concentrations in patients with end-stage renal disease (ESRD). A total of 36 patients with ESRD undergoing chronic HD/HDF treatment were enrolled (21 high-flux-HD/Fx60 membrane, 7 high-flux-HD/Elisio19H membrane, and 8 HDF/Elisio19H membrane). On a midweek session, blood samples were obtained before, at halftime, and post-treatment. Dialysate samples were obtained 4 times during treatment. Serum and dialysate CAF, cystatin C, urea, and creatinine concentrations were measured. Reduction ratios (RRs), totalsolute removal, overall dialytic clearance, and instantaneous dialytic clearance at halftime were calculated and compared. Although HD/Elisio19H and HDF/Elisio19H treatments significantly reduced CAF concentrations (RR 46.6±9.1% and 57.6±11.7%, respectively, P=0.018 and P=0.001), HD/Fx60 treatment did not remove CAF from serum (RR 2.4±15.4%, P=0.25), there was no relevant CAF detection in dialysate. In the HD/Fx60 group, the RR of CAF was significantly lower compared with cystatin C, urea, and creatinine, in which significant removal was detected (37.9±14.8%, 65.0±10.7%, and 56.0±9.8%, respectively, P<0.001). CAF is a new biomarker for kidney function whose serum concentration is not influenced by conventional high-flux HD using Fx60 membrane. It might therefore represent a promising dialysis-independent biomarker for evaluation of kidney function, for example, in acute kidney failure.

Comparison between On-Line High-Efficiency Hemodiafiltration and Conventional High-Flux Hemodialysis for Polyclonal Free Light Chain Removal

Background: Polyclonal free light chains (FLC) are considered as middle molecular weight uremic toxins in chronic kidney disease. In this study, we investigate polyclonal FLC removal by comparing conventional high-flux hemodialysis (HD) and online high-efficiency hemodiafiltration (ol-HDF) in end-stage renal disease patients. Methods: We analyzed 31 chronic dialysis patients who were treated by HD then by postdilution ol-HDF during a prospective study. All patients were anuric and without monoclonal gammopathy. Serum pre- and postdialysis FLC were collected during 4 sessions: 1 HD session and 3 ol-HDF sessions. We calculated the reduction ratio using kinetic modeling. Results: The κ reduction ratio was higher with ol-HDF than with HD (66 ± 14 vs. 52 ± 13%, p < 0.001). However, the λ reduction ratio was not significantly higher with ol-HDF (37 ± 20 vs. 37 ± 15%, p = 0.67). Furthermore, predialysis κ- and λ-FLC increased with ol-HDF compared with HD (κ 155 ± 82 vs. 87 ± 47 mg/l, p < 0.05; λ 101 ± 46 vs. 72 ± 41 mg/l, p < 0.05). Postdialysis FLC levels were raised only for λ-FLC with ol-HDF (74 ± 39 vs. 53 ± 31 mg/l, p < 0.05) and were not significantly different for κ. Conclusions: This study shows that κ-FLC removal is better in ol-HDF compared with HD, whereas there is no difference in λ-FLC removal. Surprisingly, predialysis κ and λ levels are both increased in ol-HDF, which is disturbing since polyclonal excess of λ-FLC is associated with mortality in chronic kidney disease.

Removal of Protein‐Bound, Hydrophobic Uremic Toxins by a Combined Fractionated Plasma Separation and Adsorption Technique

Protein-bound uremic toxins, such as phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate, contribute substantially to the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD). However, based on their protein binding, these hydrophobic uremic toxins are poorly cleared during conventional dialysis and thus accumulate in CKD-5D patients. Therefore, we investigated whether hydrophobic and cationic adsorbers are more effective for removal of protein-bound, hydrophobic uremic toxins than conventional high-flux hemodialyzer. Five CKD-5D patients were treated using the fractionated plasma separation, adsorption, and dialysis (FPAD) system for 5 h. A control group of five CKD patients was treated with conventional high-flux hemodialysis. Plasma concentrations of phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate were measured. Removal rates of FPAD treatment in comparison to conventional high-flux hemodialysis were increased by 130% for phenylacetic acid, 187% for indoxyl sulfate, and 127% for p-cresol. FPAD treatment was tolerated well in terms of clinically relevant biochemical parameters. However, patients suffered from mild nausea 2 h after the start of the treatment, which persisted until the end of treatment. Due to the high impact of protein-bound, hydrophobic uremic toxins on progression of CKD and CVD in CKD-5D patients, the use of an adsorber in combination with dialysis membranes may be a new therapeutic option to increase the removal rate of these uremic toxins. However, larger, long-term prospective clinical trials are needed to demonstrate the impact on clinical outcome.

Evaluation of a New Method for Pulse Push/Pull Hemodialysis

The repetition of forward and backward filtration during hemodialysis (HD) increases convective mass transfer, and thus, the authors devised a method of achieving cyclic repletion of ultrafiltration and backfiltration. Hemodialytic efficiencies of the developed unit are described. The devised method, named pulse push/pull hemodialysis (PPPHD), is based on the utilization of dual pulsation in a dialysate stream. Clearances of solutes with different molecular weights were determined, and in vivo hemodialytic performance was investigated in a canine renal failure model. Urea and creatinine reduction and albumin (ALB) loss were monitored, and the results obtained were compared with those of a conventional high-flux hemodialysis (CHD). Dialysis sessions were repeated eight times for PPPHD and six times for CHD by alternating PPPHD and CHD sessions in a single animal, which remained stable throughout the experiments. Urea and creatinine reductions for the PPPHD unit were 49.2 ± 2% and 44.3 ± 3.3%, respectively, which were slightly higher than those obtained for the CHD. Total protein and ALB levels were preserved by both methods. However, in vitro results revealed that PPPHD achieved significantly greater inulin clearance than CHD. The developed PPPHD unit facilitates repetitive filtration and improves convective mass transfer during HD, without the need for external replacement infusion.

FGF-23 removal is improved by on-line high-efficiency hemodiafiltration compared to conventional high flux hemodialysis

Reducing circulating levels of fibroblast growth factor-23 (FGF-23) in patients on renal replacement therapy (RRT) could appear as an appealing approach for cardiovascular events prevention. The purpose of our study was to compare the clearance of FGF-23 between high flux hemodialysis (HD) and on-line hemodiafiltration (OL-HDF) procedures. Fifty-three patients were included in the HD group while 32 patients were included in the OL-HDF group. Serum pre- and post-dialysis FGF-23 levels were measured using a 2nd generation Human FGF-23 (C-Term) ELISA kit. Mean FGF-23 reduction rates were significantly higher in OL-HDF (55.7 ± 25.2%) versus HD (36.2 ± 28.6%) groups (P=.0001), as were calculated FGF-23 clearances (P=.015) and Kt/V-FGF-23 (P=.001). Overall, post-treatment FGF-23 levels were significantly lower than pre-treatment values in both groups (P<.01). OL-HDF achieves higher FGF-23 removal over high flux HD.

Mathematical analysis for internal filtration of convection-enhanced high-flux hemodialyzer

Structural modifications using a conventional hemodialyzer improved the internal filtration and clearance of middle molecular weight wastes by enhanced convection effect. In this study, we employed a mathematical model describing the internal filtration rate as well as the hemodynamic and hematologic parameters in highflux dialyzer to interpret the previous reported experimental results. Conventional high-flux hemodialysis and convection-enhanced high-flux hemodialysis were configured in the mathematical forms and integrated into the iterative numerical method to predict the internal filtration phenomena inside the dialyzers during dialysis. The distributions of blood pressure, dialysate pressure, oncotic pressure, blood flow rates, dialysate flow rates, local ultrafiltration, hematocrit, protein concentration and blood viscosity along the axial length of dialyzer were calculated in order to estimate the internal filtration volume. The results show that the filtration volumes by internal filtration is two times higher in a convection-enhanced high-flux hemodialyzer than in a conventional high-flux hemodialzer and explains the experimental result of improved clearance of middle molecular size waste in convection-enhanced high-flux hemodialyzer.

Pulse Push/Pull Hemodialysis: In Vitro Study on New Dialysis Modality With Higher Convective Efficiency

Midsize molecule retention is related with renal-failure-associated mortality. Here, the authors describe a new dialysis modality, pulse push/pull hemodialysis (PPPHD), which increases convective clearance. Blood and dialysate are circulated by a pulsatile pump, but with pulsatile flow patterns that are 180 degrees out of phase. This causes blood-to-dialysate pressure gradients that oscillate between positive and negative, and which cause consecutive periods of ultrafiltration and backfiltration. The devised PPPHD was compared with conventional high-flux hemodialysis (CHFHD) in terms of solute clearances, albumin loss, and total protein levels. Human plasma containing dissolved uremic marker molecules was used as a blood substitute, and clearances were investigated for blood urea nitrogen, creatinine, vitamin B12, and inulin. Observed clearances were found to be significantly higher for PPPHD by approximately 3-14% for low-molecular-weight solutes, by 47-48% for vitamin B12, and by 38-49% for inulin than for CHFHD. No albumin loss was observed in either of these two study groups. The authors conclude that PPPHD offers a simple straightforward means of enhancing uremic molecule removal by increasing total ultrafiltration volume without the need to infuse replacement fluid.

The relevance of convection in clinical practice: A critical review of the literature

Convective treatments (high-flux hemodialysis (HD), hemodiafiltration and hemofiltration) are characterized by enhanced removal of middle and large molecular weight solutes compared with conventional low-flux HD. As these molecules are claimed to play an important role in the genesis of many complications of chronic HD, the availability of these techniques represented an intriguing innovation and a possible means to improve the still poor prognosis of HD patients. Here we will critically review the most important published studies comparing convective treatments with low-flux HD on chronic morbidity, preservation of residual renal function, and long-term survival.