High-volume Hemodiafiltration Research Articles

High-Volume Hemodiafiltration and Cool Hemodialysis Have a Beneficial Effect on Intradialytic Hemodynamics: A Randomized Cross-Over Trial of Four Intermittent Dialysis Strategies

IntroductionCompared to standard hemodialysis (S-HD), postdilution hemodiafiltration (HDF) has been associated with improved survival.MethodsTo assess whether intradialytic hemodynamics may play a role in this respect, 40 chronic dialysis patients were cross-over randomized to S-HD (dialysate temperature [Td] 36.5 °C), cooled HD (C-HD; Td 35.5 °C), and HDF (low-volume [LV-HDF)] and high-volume [HV-HDF], both Td 36.5 °C, convection volume 15 liters, and at least 23 liters per session, respectively), each for 2 weeks. Blood pressure (BP) was measured every 15 minutes. The primary endpoint was the number of intradialytic hypotensive (IDH) episodes per session. IDH was defined as systolic BP (SBP) less than 90 mmHg for predialysis SBP less than 160 mmHg and less than 100 mmHg for predialysis SBP greater than or equal to 160 mmHg, independent of symptoms and interventions. A post hoc analysis on early-onset IDH was performed as well. Secondary endpoints included intradialytic courses of SBP, diastolic BP (DBP) and mean arterial pressure (MAP).ResultsDuring S-HD, IDH occurred 0.68 episodes per session, which was 3.2 and 2.5 times higher than during C-HD (0.21 per session, P < 0.0005) and HV-HDF (0.27 per session, P < 0.0005), respectively. Whereas the latter 2 strategies showed similar frequencies, HV-HDF differed significantly from LV-HDF (P = 0.02). A comparable trend was observed for early-onset IDH: S-HD (0.32 per session), C-HD (0.07 per session, P < 0.0005) and HV-HDF (0.10 per session, P = 0.001). SBP, DBP, and MAP declined during S-HD (−6.8, −5.2, −5.2 mmHg per session; P = 0.004, P < 0.0005, P = 0.002 respectively), which was markedly different from C-HD (P < 0.01).ConclusionThough C-HD and HV-HDF showed the lowest IDH frequency and the best intradialytic hemodynamic stability, all parameters were most disrupted in S-HD. Therefore, the survival benefit of HV-HDF over S-HD may be partly caused by a more beneficial intradialytic BP profile.

The high-volume haemodiafiltration vs high-flux haemodialysis registry trial (H4RT): a multi-centre, unblinded, randomised, parallel-group, superiority study to compare the effectiveness and cost-effectiveness of high-volume haemodiafiltration and high-flux haemodialysis in people with kidney failure on maintenance dialysis using linkage to routine healthcare databases for outcomes

BackgroundMore than a third of the 65,000 people living with kidney failure in the UK attend a dialysis unit 2–5 times a week to have their blood cleaned for 3–5 h. In haemodialysis (HD), toxins are removed by diffusion, which can be enhanced using a high-flux dialyser. This can be augmented with convection, as occurs in haemodiafiltration (HDF), and improved outcomes have been reported in people who are able to achieve high volumes of convection. This study compares the clinical- and cost-effectiveness of high-volume HDF compared with high-flux HD in the treatment of kidney failure.MethodsThis is a UK-based, multi-centre, non-blinded randomised controlled trial. Adult patients already receiving HD or HDF will be randomised 1:1 to high-volume HDF (aiming for 21+ L of substitution fluid adjusted for body surface area) or high-flux HD. Exclusion criteria include lack of capacity to consent, life expectancy less than 3 months, on HD/HDF for less than 4 weeks, planned living kidney donor transplant or home dialysis scheduled within 3 months, prior intolerance of HDF and not suitable for high-volume HDF for other clinical reasons. The primary outcome is a composite of non-cancer mortality or hospital admission with a cardiovascular event or infection during follow-up (minimum 32 months, maximum 91 months) determined from routine data. Secondary outcomes include all-cause mortality, cardiovascular- and infection-related morbidity and mortality, health-related quality of life, cost-effectiveness and environmental impact. Baseline data will be collected by research personnel on-site. Follow-up data will be collected by linkage to routine healthcare databases — Hospital Episode Statistics, Civil Registration, Public Health England and the UK Renal Registry (UKRR) in England, and equivalent databases in Scotland and Wales, as necessary — and centrally administered patient-completed questionnaires. In addition, research personnel on-site will monitor for adverse events and collect data on adherence to the protocol (monthly during recruitment and quarterly during follow-up).DiscussionThis study will provide evidence of the effectiveness and cost-effectiveness of HD as compared to HDF for adults with kidney failure in-centre HD or HDF. It will inform management for this patient group in the UK and internationally.Trial registrationISRCTN10997319. Registered on 10 October 2017

Clinical performance, intermediate and long-term outcomes of high-volume hemodiafiltration in patients with kidney failure.

Hemodiafiltration (HDF), in which both convective and diffusion methods are combined, yields an increased overall solute clearance compared with hemodialysis (HD), specifically for medium and larger molecular weight uremic toxins. Due to uncertainty in the treatment effects, the nephrology community still perceives the implementation of HDF and the achievement of high convective volume as complex. In this article, we review practical aspects of the implementation of HDF that can effectively deliver a high-volume HDF therapy and assure clinical performance to most patients. We also present an overview of the impact of high-volume HDF (compared to HD) on a series of relevant biochemical, patient-reported, and clinical outcomes, including uremic toxin removal, phosphate, Inflammation and oxidative stress, hemodynamic stability, cardiac outcomes, nutritional effects, health-related quality of life, morbidity, and mortality.

Mortality in High-Flux Hemodialysis vs. High-Volume Hemodiafiltration in Colombian Clinical Practice: A Propensity Score Matching Study

Background: The aim was to compare the effects of high-flux hemodialysis (HF-HD) versus high-volume post-dilution hemodiafiltration (HV-HDF) on mortality risk. Methods: Retrospective observational study of prevalent patients on hemodialysis who were followed for two years and treated in 28 kidney centers in Colombia. In this study, we included all adult patients who had been on dialysis for at least 90 days treated with an arteriovenous fistula. They were classified as HF-HD if they underwent this treatment exclusively (100% of time). For HV-HDF, if they received this treatment in more than 90% of the observation period. The primary outcome variable was mortality, and the type of hemodialysis therapy was considered as the exposure variable. Propensity score matching (PSM) and Cox regression models were used to evaluate the effect of dialysis modality on the mortality risk. Results: A total of 2933 patients were analyzed, 2361 patients with HF-HD and 572 with HV-HDF. After PSM, 1010 prevalent patients remained; mortality rate was 14.2% (95% Confidence Interval—CI: 11.3–17.6%) and 5.9% (95%CI: 4.0–8.4%) in HF-HD and HV-HDF group, respectively. HV-HDF therapy was associated with a 55% reduction in mortality compared with the HF-HD group (Hazards ratio-HR: 0.45 [95%CI 0.32–0.64] p &lt; 0.001). Cardiovascular mortality rate was not statistically different between groups (HF-HD: 7.1% (36), HV-HDF: 3.4% (17), HR: 0.51 (95%CI: 0.21–1.28), p: 0.152). However, in patients younger than 60 years, a beneficial effect was observed in favor to HV-HDF therapy with a 79% reduction in cardiovascular mortality risk (HR: 0.21, (95%CI: 0.05–0.79), p: 0.021). Conclusion: After adjustment for different confounders, this study suggests that HV-HDF could reduce all-cause mortality compared to HF-HD therapy in prevalent patients on hemodialysis.

MO653: High-Flux Haemodialysis and Haemodiafiltration: A Comparative Study Based on 1-H NMR Serum Metabolic Profile

Abstract BACKGROUND AND AIMS Patients with chronic kidney disease (CKD) accumulate uraemic toxins (UTs). When compared to other conventional dialysis modalities, high volume haemodiafiltration (HDF) improves the removal of medium and low molecular weight UTs. The present study is a post-hoc analysis comparing the metabolomic profile in serum from patients under high flux HD (hf-HD) and HDF in HDFIT, a multicentric randomized controlled trial (RCT). METHOD Random (pre- and post-dialysis) samples from nine patients in a study arm were selected at baseline and at the end of the follow-up. To compare the samples, 26 possibly matching metabolites were identified by a t-test among the four groups using 1-H nuclear magnetic resonance (NMR). To evaluate the comparison between the modalities in a single treatment session, the clearance rates (CRs) of each metabolite were calculated based on pre- and post-dialysis samples. In addition, to evaluate the effect of UTs removal during the trial follow-up period, the pre-dialysis metabolite concentrations both at the baseline and 6 months were compared with the two arms of the study. RESULTS Evaluating the concentrations of the metabolites during the follow-up period for each study arm, it was possible to assess the effects of UTs removal during the study for each modality. The comparison of the intensity of the peaks identified 26 possible metabolites that differentiated hf-HD and HDF in this timeframe. The correlation (see Figure 1a) then suggested that the peak integrals of 16 of these metabolites increased from baseline to 6 months in the hf-HD, but not in the HDF arm. Amongst the metabolites, several are involved in important metabolic pathways, such as the metabolisms of phenylalanine and the biosynthesis of phenylalanine, tyrosine and tryptophan, which both relate to UTs and the development of cardiovascular diseases. The peak integration relative to glycolic acid was significantly higher (P&amp;lt;.05) at 6 months than at baseline (see Figure 1b) in the hf-HD than in the HDF arm, which has been related to an increased number of renal failure and of renal insufficiency cases [1,2], as well as it related to liver damage [3]. CONCLUSION The concentrations of metabolites related both to CKD and associated pathologies were stable in the HDF arm only during the follow-up period, suggesting enhancement of the long-term stability by this method. In the hf-HD long-term follow-up, the relative increase in the glycolic acid peak integration area, which is related to the metabolite concentration, has also previously been linked to an increased number of renal failures and renal insufficiency cases and to liver damages.

MO124: Intradialytic Symptomatology is Largely Patient-Specific in both Haemodialysis and Haemodiafiltration: A Randomized Cross-Over Trial between Four Intermittent Dialysis Modalities

Abstract BACKGROUND AND AIMS Standard haemodialysis is associated with a considerable burden of intradialytic symptoms. Although haemodialysis with cool dialysate is associated with less intradialytic discomfort in general, the incidence of cold sensations increases significantly. Whether treatment with online post-dilution high-volume haemodiafiltration [target convection volume (CV) ≥23 L/session] reduces adverse intradialytic symptoms and provokes cold sensations is unknown. METHOD We performed a randomized controlled cross-over trial in 40 prevalent dialysis patients, who were subjected to two haemodialysis modalities: standard haemodialysis [sHD; dialysate temperature (Td) of 36.5°C] and cool haemodialysis (cHD; Td 35.5°C) and two haemodiafiltration modalities: low-volume haemodiafiltration (lvHDF, CV 15 L/1.73 m2/session, Td 36.5°C) and high-volume haemodiafiltration (hvHDF, CV ≥23 L/1.73 m2/session, Td 36.5°C). Every dialysis modality lasted 2 weeks. Intradialytic symptoms were evaluated after the last session of each dialysis modality, with a slightly modified Dialysis Symptom Index (mDSI). Intradialytic thermal sensations were scored on the Visual Analogue Scale Thermal Perception (VAS-TP) before and after 1 and 3 h of each treatment session. Patients were trained to use the mDSI and VAS-TP, in order to reduce incidental stress and unwanted learning responses due to the trial environment. Repeated measures analysis of variance (ANOVA) and one-way ANOVA were used to measure potential differences in intradialytic symptoms between the dialysis modalities (intraindividual differences) and to assess potential interindividual differences in intradialytic symptoms. Linear mixed models with an interaction term between time and modality were used to determine differences in rate of change of VAS-TP between the four modalities. When appropriate, stratified models were fitted subsequently. RESULTS With the exception of cold sensations during cHD (P = .01), intradialytic symptoms did not differ between modalities, but varied markedly between patients (P &amp;lt; .05 in 11/13 items, Table 1). While the VAS-TP score remained unaltered in sHD, lvHDF and hvHDF, patients felt significantly more cold sensations during cHD (P = .007)(Figure 1). Stratified models showed a decrease of 0.43 points/h on the VAS-TP scale (P = .007) in the first hour of cHD and remained unaltered thereafter [+0.10 points/h (P = .20)]; thermal perception remained unaltered [0.04 points/h (P = .77)] in the other modalities. CONCLUSION Intradialytic symptomatology was, except for the symptom feeling cold, by and large similar in all modalities, but it varied markedly between patients. Hence, adverse intradialytic symptoms seem largely patient-specific. Patients experienced more cold sensations during cool HD, but not during haemodiafiltration.

MO642: Comparison of Medium Cut-Off Dialyzer and Post-Dilution Hemodiafiltration on the Removal of Small and Middle Molecule Uremic Toxins

Abstract BACKGROUND AND AIMS The medium cut-off (MCO) dialyzer increases the removal of several middle molecules more effectively than high-flux hemodialysis (HD). However, there are no comparable data on the efficacy and safety of MCO dialyzers versus post-dilution hemodiafiltration (HDF) in Korean patients. METHOD A total of 9 patients with chronic HD were included in this crossover study. Patients received HD with an MCO dialyzer for 4 weeks, followed by a 2-week washout period, using a high-flux dialyzer to minimize carry-over effects and then crossed over to post-dilution HDF for 4 weeks. Reduction ratios and differences in the values before and after were calculated from the MCO dialysis, post-dilution HDF and high-flux HD. In the in vitro study, EA.hy926 cells were treated with dialyzed serum. RESULTS Compared with post-dilution HDF, the MCO dialyzer achieved significantly higher reduction ratios for larger middle molecules [myoglobin, kappa free light chain (κFLC) and lambda FLC (λFLC)]. Similarly, the differences between before and after the last dialysis session of myoglobin, κFLC, and λFLC were significantly greater in MCO dialysis than in post-dilution HDF. The expression of Bax and nuclear factor-κb was decreased in the serum after dialysis with the MCO dialyzer than with HDF. CONCLUSION Compared with high-volume post-dilution HDF, MCO dialysis showed no differences in the removal of molecules below 12 000 Da, whereas it was superior in the removal of larger uremic middle molecule toxins in patients with kidney failure. Moreover, these results might be expected to have an anti-apoptotic effect on the human endothelium.

MO657: Low Incidence of Intradialytic Hypotension During Online Post-Dilution High-Volume Haemodiafiltration: A Randomized Cross-Over Trial between Four Intermittent Dialysis Modalities

Abstract BACKGROUND AND AIMS Compared with standard haemodialysis (S-HD), online post-dilution haemodiafiltration (HDF) is associated with improved survival, especially when high convection volumes [high-volume (HV)-HDF] are achieved [1]. A superior intradialytic haemodynamic stability may play an important role in this respect. Therefore, we assessed whether the intradialytic haemodynamic profile differs between four dialysis modalities, including S-HD and HV-HDF. METHOD In the current randomized cross-over trial (NCT03249532, ClinicalTrials.gov), 40 prevalent dialysis patients were subjected to S-HD [dialysate temperature (Td) 36.5°C], HD with cool dialysate (C-HD; Td 35.5°C), low-volume (LV)-HDF [convection volume (CV) 15 L/1.73 m2/session) and HV-HDF (CV ≥23 L/1.73 m2/session) (both Td 36.5°C). Blood pressure (BP) was measured 4x/hour. The primary endpoint was the total number of intradialytic hypotensive (IDH) episodes. IDH was defined as a nadir in systolic BP (SBP) &amp;lt;90 mmHg for a pre-dialysis SBP &amp;lt;160 mmHg and &amp;lt;100 mmHg for a pre-dialysis SBP ≥160 mmHg, independent of symptoms and interventions. In addition, an explorative analysis was performed on the incidence of early-onset IDH, which has recently been related to mortality [2]. Secondary endpoints included the intradialytic courses of SBP, diastolic BP (DBP) and mean arterial pressure (MAP). RESULTS IDH occurred significantly less frequent during C-HD (0.21 episodes/session) and HV-HDF (0.27/session) compared with S-HD (0.68/session, both P &amp;lt; .0005) (Figure 1). Furthermore, early-onset of IDH was also observed more frequently during S-HD (0.32/session) than during C-HD (0.07/session, P&amp;lt;.0005) or HV-HDF (0.10/session, P = .001) (Figure 1). After correction for multiple testing, the intradialytic courses of SBP, DBP and MAP declined only significantly during S-HD (−6.8, −5.2, −5.2 mmHg/session; P = .004, &amp;lt;.0005, .002 resp.) whereas these remained stable in the other modalities (Table 1). CONCLUSION In conclusion, during both C-HD and HV-HDF, IDH occurred least frequent and the intradialytic haemodynamic stability was best preserved. In contrast, intradialytic haemodynamic stability is most dysregulated during S-HD. Therefore, it is conceivable that the survival benefit of HV-HDF over S-HD is (at least partly) due to a more stable intradialytic haemodynamic profile and consequently less repetitive tissue injury.

Basic prerequisites for on-line, high-volume hemodiafiltration.

High-volume hemodiafiltration involves filtration of >23 L/treatment and its replacement by sterile non-pyrogenic substitution fluid, while maintaining the patient's fluid balance. That volume of substitution fluid precludes the use of prepackaged sterile fluid. Instead, substitution fluid must be prepared on-line using machines that incorporate a series of bacteria- and endotoxin-retentive filters. The sterilizing ultrafilters are validated to deliver sterile, non-pyrogenic fluid to the patient when operated according to the machine manufacturer's instructions and in compliance with international standards and regulatory oversight. A successful hemodiafiltration program also places important responsibilities on the user. Specifically, the user is responsible for ensuring that the dialysis water or dialysis fluid delivered to the sterilizing filters of the hemodiafiltration machine meets the machine manufacturer's specifications and is consistent with the quality used in the sterilization validation process. The user is also responsible for ensuring that the treatment prescription allows a filtration volume >23 L/treatment to be achieved by careful selection of a dialyzer, blood flow rate and treatment time. Questions related to assurance that the substitution fluid will routinely be sterile and non-pyrogenic have limited the uptake of on-line hemodiafiltration as a therapeutic option in some countries, such as the United States.

High-volume hemodiafiltration decreases the pre-dialysis concentrations of indoxyl sulfate and p-cresyl sulfate compared to hemodialysis: a post-hoc analysis from the HDFit randomized controlled trial.

Although high-volume online hemodiafiltration has been associated with higher clearance and lower pre-dialysis concentration of middle molecular weight toxins compared to hemodialysis, its effect on protein-bound uremic toxins has shown inconclusive results. In this study, we investigated whether hemodiafiltration impacts pre-dialysis plasma levels of the toxins indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid compared to high-flux hemodialysis. This is a post-hoc analysis of the multicenter, randomized controlled trial HDFit (ClinicalTrials.gov: NCT02787161). Uremic toxins were determined by high performance liquid chromatography at baseline, 3, and 6months. Mean differences in monthly changes of pre-dialysis uremic toxin concentrations between hemodiafiltration and high-flux hemodialysis were analyzed using linear mixed-effect models. One hundred ninety-three patients (mean age 53years old, 71% males) were analyzed. There were no differences between groups regarding clinical and biochemical characteristics at baseline or duration of dialysis session and blood flows throughout the follow-up. Mean differences in rates of change (μM/month, [confidence interval CI]) in high-flux hemodialysis vs. hemodiafiltration were 2.4 [0.3 to 4.56], 3.94 [- 1.54 to 9.41] and 0.06 [- 0.6 to 0.5] for indoxyl sulfate, p-cresyl sulfate and indole-3-acetic acid, respectively. In the exploratory analysis, these differences in high-flux hemodialysis vs. hemodiafiltration subgroup with convective volume > 27.5L were 2.86 [0.43 to 5.28], 7.43 [0.7 to 14.16] and - 0.19 [- 0.88 to 0.50]. These exploratory findings suggest that hemodiafiltration is more effective in reducing indoxyl sulfate as compared to standard high-flux hemodialysis, and also that this effect was extended to p-cresyl sulfate in patients achieving higher convective volumes.

Why should we focus on high-volume hemodiafiltration?

Though noticeable technological advances related to hemodialysis (HD) have been made, unfortunately, the survival rate of dialysis patients has yet to improve significantly. However, recent research findings reveal that online hemodiafiltration (HDF) significantly improves patient survival in comparison to conventional HD. Accordingly, the number of patients receiving online HDF is increasing. Although the mechanism driving the benefit has not yet been fully elucidated, survival advantages are mainly related to the lowering of cardiovascular mortality. High cardiovascular mortality among HD patients is seemingly attributable to the cardiovascular changes that occur in response to renal dysfunction and the HD-induced myocardial stress and injury, and online HDF appears to improve such secondary cardiovascular changes. Interestingly, patient survival improves only if the convection volume is supplied sufficiently over a certain level during online HDF treatment. In other words, survival improvement from online HDF is related to convection volume. Therefore, there is a growing interest in high-volume HDF in terms of improving the survival rate. The survival improvement will require a minimum convection volume of 23 L or more per 4-hour session for postdilution HDF. To obtain an optimal high convection volume in online HDF, several factors, such as the treatment time, blood flow rate, filtration fraction, and dialyzer, need to be considered. High-volume HDF can be performed easily and safely in routine clinical practice. Therefore, when the required equipment is available, performing high-volume HDF will help to improve the survival rate of dialysis patients.

High volume online post-dilution hemodiafiltration: how relevant is it in chronic kidney disease?

ABSTRACTOnline hemodiafiltration is potentially a superior mode of dialysis compared to conventional hemodialysis. However, prospective randomized controlled trials have failed to demonstrate such superiority. Post-hoc analyses of these trials have indicated that high volume post-dilution hemodiafiltration is associated with lower death rates than conventional dialysis. This study discusses whether the lower death rates ascribed to high volume hemodiafiltration are linked to convection volume or the time on dialysis needed to achieve high convection volumes.

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.

Why and how high volume hemodiafiltration may reduce cardiovascular mortality in stage 5 chronic kidney disease dialysis patients? A comprehensive literature review on mechanisms involved.

Online hemodiafiltration (HDF) is an established renal replacement modality for patients with end stage chronic kidney disease that is now gaining rapid clinical acceptance worldwide. Currently, there is a growing body of evidence indicating that treatment with HDF is associated with better outcomes and reduced cardiovascular mortality for dialysis patients. In this comprehensive review, we provide an update on the potential mechanisms which may improve survival in HDF treated patients. The strongest evidence is for better hemodynamic stability and reduced endothelial dysfunction associated with HDF treatments. Clinically, this is marked by a reduced incidence of intradialytic hypotensive episodes, with a better hemodynamic response to ultrafiltration, mediated by an increase in total peripheral vascular resistance and extra-vascular fluid recruitment, most likely driven by the negative thermal balance associated with online HDF therapy. In addition, endothelial function appears to be improved due to a combination of a reduction of the inflammatory and oxidative stress complex syndrome and exposure to circulating cardiovascular uremic toxins. Reports of reversed cardiovascular remodeling effects with HDF may be confounded by volume and blood pressure management, which are strongly linked to center clinical practices. Currently, treatment with HDF appears to improve the survival of dialysis patients predominantly due to a reduction in their cardiovascular burden, and this reduction is linked to the sessional convection volume exchanged.

A Matched Case-Control Study of Noncholesterol Sterols and Fatty Acids in Chronic Hemodialysis Patients.

Dyslipidemia is common among patients on hemodialysis, but its etiology is not fully understood. Although changes in cholesterol homeostasis and fatty acid metabolism play an important role during dialysis, the interaction of these metabolic pathways has yet to be studied in sufficient detail. In this study, we enrolled 26 patients on maintenance hemodialysis treatment (high-volume hemodiafiltration, HV HDF) without statin therapy (17 men/9 women) and an age/gender-matched group of 26 individuals without signs of nephropathy. The HV-HDF group exhibited more frequent signs of cardiovascular disease, disturbed saccharide metabolism, and altered lipoprotein profiles, manifesting in lower HDL-C, and raised concentrations of IDL-C and apoB-48 (all p < 0.01). HV-HDF patients had higher levels of campesterol (p < 0.01) and β-sitosterol (p = 0.06), both surrogate markers of cholesterol absorption and unchanged lathosterol concentrations. Fatty acid (FA) profiles were changed mostly in cholesteryl esters, with a higher content of saturated and n-3 polyunsaturated fatty acids (PUFA) in the HV-HDF group. However, n-6 PUFA in cholesteryl esters were less abundant (p < 0.001) in the HV-HDF group. Hemodialysis during end-stage kidney disease induces changes associated with higher absorption of cholesterol and disturbed lipoprotein metabolism. Changes in fatty acid metabolism reflect the combined effect of renal insufficiency and its comorbidities, mostly insulin resistance.

Comparative metabolomic study of high-flux hemodialysis and high volume online hemodiafiltration in the removal of uremic toxins using 1H NMR spectroscopy

Uremic toxins (UTs) accumulate in the circulation of patients with chronic kidney disease (CKD). High volume hemodiafiltration (HDF) improves clearance of low and medium molecular weight UTs compared to HD. The present study is a post-hoc analysis comparing the metabolomic profile in serum from patients under high flux HD (hf-HD) and HDF in HDFIT, a multicentric randomized controlled trial (RCTs). Per protocol, serum samples were collected pre- and post- dialysis treatments at randomization (baseline) and at the end of the follow up (6 months) and stored in a biorepository. Random (pre- and post-dialysis) samples from nine patients in study arm were selected at baseline and at the end of the follow up. To compare the samples, 26 possibly matching metabolites were identified by a t-test among the four groups using 1H nuclear magnetic resonance (NMR). To evaluate the comparison between the modalities is a single treatment session, the clearance rates (CRs) of each metabolite were calculated based on pre-dialysis and post-dialysis samples. In addition, to evaluate to effect of UT removal during the trial follow up period, the pre-dialysis metabolite concentrations at the baseline and at 6 months were compared among the two arms of the study. There was no significant difference between in the single session CRs of metabolites when hf-HD and HDF were compared. On the other hand, the comparison between baseline and 6-month (long-term evolution) led to the identification of 16 metabolites that differentiated the hf-HD and the HDF evolutions. Most of these 16 metabolites are involved in several important metabolic pathways, such as metabolism of phenylalanine and biosynthesis of phenylalanine, tyrosine, and tryptophan, which are related to UTs and cardiovascular disease development. Although no difference was observed between hf-HD and HDF samples before and after a single session, concentrations of CKD-relevant metabolites and associated pathologies were stable in the HDF samples, but not in the hf-HD samples, over the six-month period, suggesting that HDF enhances long-term stability.

Potential Cost Savings Associated with the Reduction of Hospital Admissions by Using Online High-Volume Hemodiafiltration (Hv-HDF) vs. High-Flux hemodialysis (Hf-HD)

Potential Cost Savings Associated with the Reduction of Hospital Admissions by Using Online High-Volume Hemodiafiltration (Hv-HDF) vs. High-Flux hemodialysis (Hf-HD)

The Effect of Hemodiafiltration on Inflammatory Biomarkers in Comparison to High Flux Dialyzers in Prevalent Hemodialysis Patients

Abstract Introduction Inflammation in patients with ESRD undergoing HD is an increasing concern for physicians and has been related to increase the rates of morbidity and mortality. Interestingly, patients with ESRD in conventional HD have frequent infections and a suboptimal response to vaccines; this is probably related to an immune inflammatory disorder associated either with uremia and/or nutritional status. In addition to CRP, which seems to be the most important marker for the identification and control of inflammation in clinical practice, many other markers are also available for the evaluation of inflammatory state. Decreased renal clearance clearly accounts for higher levels of circulating cytokines, although increased production has also been described. Hemodiafiltration has been shown to improve cardio-protection and the immunologic system and reduces infection and mortality compared with conventional HD. A recent study showed that hemodiafiltration compared with conventional HD reduced the risk of mortality in ESRD patients. Analysis of pooled individual participant data from randomized controlled trials has shown survival benefits of high volume-HDF on all-cause mortality and especially cardiovascular mortality rate. The mechanisms that lead to improved outcomes are not clear, but it is thought that HDF may reduce the production of inflammatory mediators through the use of biocompatible dialysers and ultrapure dialysate and also improve clearance of larger molecular weight substances, many of which are associated with oxidative stress, inflammation and endothelial dysfunction. Objective The aim of this study is to detect, prospectively, the effect of 3 months dialysis with Hemodiafiltration on inflammatory and nutritional biomarkers in comparison to conventional dialysis with high flux dialyzer in stable HD patients. Patients and methods 30 adults aged 20-75 years who were selected from Dialysis Unit, Kobary El-Kobba Military Hospital. 30 male patients known to have chronic kidney disease and are on dialysis with high flux dialyzer more than 3 months were divided into 2 groups:15 Patients are shifted to be on dialysis with HDF and 15 Patients are continued to be on Regular Hemodialysis with high flux dialyzer. Full medical history and clinical examination. Anthropometric measurements and Laboratory investigations including Complete Blood Picture (WBCs, platelets, Hb), Coagulation profile PT, PTT&amp;INR, Liver function tests (ALT, AST, T. Bilirubin and S. Albumin), Lipid profile (Triglycerides, total cholesterol, VLDL), S. creatinine, BUN, Na, K, Uric acid, Total Proteins, Serum Calcium, Serum Phosphorus, PTH, Serum ferritin, High sensitivity CRP (Enzyme- Linked Immunosorbent Assay (ELISA)) and IL6 (ELISA). Results The current study was conducted on 30 patients with chronic kidney disease on regular dialysis. The patients were divided into two groups A representing patients on hemodiafiltration (n = 15) and group B representing patients on dialysis with high flux dialyzer (n = 15). A high statistical significant difference (P &amp;lt; 0.01) was found regarding K 4.3±0.6 meq/l in group A while it is 5.2±0.5 meq/l in group B, a high statistical significant difference (P &amp;lt; 0.01) was found regarding phosphorus 4.6±1.0 mg/dl in group A while it is 6.1±0.9 mg/dl in group B and no statistical significant difference (P &amp;gt; 0.05) was found as regard the uric acid. A statistical significant difference (P &amp;lt; 0.05) was found regarding CRP 63.5±40.9 mg/dl in group A while it is 73.4±33.2 mg/dl in group B, a statistical significant difference (P &amp;lt; 0.01) was found regarding IL6 85.3±37.6 mg/dl in group A while it is 156.7±151.9 mg/dl in group B after 3 months and no statistical significant difference (P &amp;gt; 0.05) was found as regard those inflammatory markers before 3 months. A statistical significant difference (P &amp;lt; 0.05) was found regarding CRP. A statistical significant difference (P &amp;lt; 0.05) was found regarding IL6. Conclusion The present study revealed that there was no significant change in CRP and IL6 in patients on HDF compared to patients undergoing hemodialysis with high flux dialyzer before 3 months but there was a significant decrease in CRP and IL6 in patients on HDF compared to patients undergoing hemodialysis with high flux dialyzer after 3 months.

Effect of various dialysis modalities on intradialytic hemodynamics, tissue injury and patient discomfort in chronic dialysis patients: design of a randomized cross-over study (HOLLANT)

BackgroundFrom a recent meta-analysis it appeared that online post-dilution hemodiafiltration (HDF), especially with a high convection volume (HV-HDF), is associated with superior overall and cardiovascular survival, if compared to standard hemodialysis (HD). The mechanism(s) behind this effect, however, is (are) still unclear. In this respect, a lower incidence of intradialytic hypotension (IDH), and hence less tissue injury, may play a role. To address these items, the HOLLANT study was designed.MethodsHOLLANT is a Dutch multicentre randomized controlled cross-over trial. In total, 40 prevalent dialysis patients will be included and, after a run-in phase, exposed to standard HD, HD with cooled dialysate, low-volume HDF and high-volume HDF (Dialog iQ® machine) in a randomized fashion. The primary endpoint is an intradialytic nadir in systolic blood pressure (SBP) of < 90 and < 100 mmHg for patients with predialysis SBP < 159 and ≥ 160 mmHg, respectively. The main secondary outcomes are 1) intradialytic left ventricle (LV) chamber quantification and deformation, 2) intradialytic hemodynamic profile of SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP), 3) organ and tissue damage, such as the release of specific cellular components, and 4) patient reported symptoms and thermal perceptions during each modality.DiscussionThe current trial is primarily designed to test the hypothesis that a lower incidence of intradialytic hypotension contributes to the superior survival of (HV)-HDF. A secondary objective of this investigation is the question whether changes in the intradialytic blood pressure profile correlate with organ dysfunction and tissue damage, and/or patient discomfort.Trial registrationRegistered Report Identifier: NCT03249532# (ClinicalTrials.gov). Date of registration: 2017/08/15.

Stepwise achievement of high convection volume in post‐dilution hemodiafiltration: A prospective observational study

High-volume online hemodiafiltration (HDF) has been reported to reduce the patient's mortality. However, achieving a high convection volume is challenging. In this prospective study, we investigated the feasibility of achieving high-volume HDF with ≥21L substitution volume via modification of blood flow rate (BFR), needle size, and dialysis membrane. In 30 patients undergoing hemodialysis, we followed a stepwise protocol and gradually increased the BFR (280→300→330ml/min; steps 1, 2, and 3) and needle size (16→15G; step 4). After changing dialyzer surface area (1.8m2 →2.5m2 ), the BFR and needle size were similarly increased stepwise (steps 5, 6, 7, and 8). The mean substitution volume was 18.7±2.2L at step 1 and it significantly increased to 25.1±2.6L by step 8. A substitution volume of 21L was achieved by 13.3% of patients in step 1 and by 96.7% after step 8. The substitution volume was higher for the dialyzer with a large surface area and for the larger needle (15G). Between steps 1 and 8, the Kt/V and β2 microglobulin reduction ratios also improved significantly. High-volume HDF is feasible through a stepwise increase in the BFR, needle size, and surface area of the dialysis membrane.