High-volume Online Hemodiafiltration Research Articles

High volume online hemodiafiltration: a global perspective and the Brazilian experience

RESUMO A hemodiafiltração (HDF) on-line é uma modalidade dialítica em rápido crescimento no mundo. No Brasil, o número de pacientes com planos de saúde privados tratados por HDF já ultrapassa aquele de pacientes em diálise peritoneal. O alcance de um alto volume convectivo associado à redução de desfechos clínicos e do risco de morte confirmam os benefícios da HDF. Dados nacionais do estudo HDFit forneceram informações práticas relevantes sobre a implementação da HDF on-line em clínicas de diálise no Brasil. O objetivo desta publicação é a disseminação de informações técnicas que possam auxiliar na utilização, com qualidade e segurança, dessa nova modalidade dialítica.

High volume online hemodiafiltration: a global perspective and the Brazilian experience.

Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

#6348 HFR USING A HIGH-FLUX DIALYZER (SUPRA-H) AS NEW EFFECTIVE ALTERNATIVE TO ON-LINE HEMODIAFILTRATION: A SINGLE SESSION ANALYSIS

Abstract Background and Aims Hemodiafiltration with regeneration of the ultrafiltrate (HFR) is a highly biocompatible dialysis technique that combines convection, diffusion, and adsorption. SUPRA-H is a new HFR system which uses a high-flux dialyzer in the diffusive stage to improve large uremic toxin removal. The aim of our study was to compare the toxin removal of the SUPRA-H system with high-volume online-hemodiafiltration (OL-HDF). Method In an open, randomized, cross-over, single-center, controlled study, 16 adult chronic hemodialysis patients were treated with SUPRA-H or OL-HDF. Hemodialysis sessions were delivered with Flexya dialysis monitor (Medtronic) in the middle-week session, lasting four hours. OL-HDF session was performed in post-dilution mode with the same high-flux dialyzer (Phylter HF17G, Medtronic) as that used in the diffusive stage of the SUPRA-H system. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of urea, creatinine, phosphate, β2-microglobulin (β2mglob), kappa (κFLC) and lambda (λFLC) free light chains, interleukin-6 (IL-6) p-Cresyl sulfate, indoxyl sulfate and albumin, was intraindividually compared for the two dialysis types with linear mixed models. Results Whereas urea RR was significantly lower, SUPRA-H had significantly higher RR for κFLC (Median: 58.63%, IQR: 49.91-70.24) than those obtained with OL-HDF (Median: 51.97%, IQR: 37.12-62.71); p = 0.03). The RRs for the other large and protein-bound uremic toxins tended to be higher with the SUPRA-H system (Figure 1). There were no significant differences in the RRs for creatinine, phosphate, IL-6, and albumin. Conclusion The new HFR system SUPRA-H, appears to be a potential technologic step ahead in terms of improved large molecule removal for dialysis patients, and might contribute to a more adequate dialysis therapy.

Evaluation of the impact of high-volume online hemodiafiltration on glycemic status, hydration status, and body fat content in diabetic patients

Abstract Background: The increasing patients with diabetes undergoing hemodialysis (HD) have concerned about the issue of glucose delivery with substitution fluid. We evaluate the effects of online high-volume hemodiafiltration (OL-HDF) versus high flux HD (HF-HD) on the influence of glycemic status and body fat content in patients with type 2 diabetes mellitus (T2DM) receiving HD. Objectives: The influence glucose in substitution fluid on glycemic status and body fat content in patients with type 2 diabetes mellitus. Methods: This study evaluated 117 patients receiving HD for more than 3 months (17 patients with T2DM receiving high-volume OL-HDF and the other 100 patients receiving HF-HD). Initially, we performed a cross-sectional study and later examined two modalities of high-volume OL-HDF in a 9-month cross-over study. Overall glycemic control was estimated from the fasting blood glucose (FBG) and the hemoglobin A1c (HbA1c) levels. Body composition and nutritional status were assessed by bioimpedance spectroscopy. Results: FBG and HbA1c were not significantly different in both groups of patients after having followed for 12 weeks. No significant differences were found in overhydration status and body fat content between the two therapy modalities. The blood hemoglobin (Hb) level increased in the high-volume OL-HDF group compared with the HF-HD group. Additionally, no differences were observed in glycemic status, body mass index, or body fat mass between both high-volume pre- and post-dilutional OL-HDF. Conclusion: High-volume OL-HDF did not have an adverse impact on glycemic status, body mass index, and body fat content in patients with diabetes undergoing HD in our short-term study. A large-scale and long-term follow-up study is required to confirm these results.

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.

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.

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.

Randomized comparison of three high-flux dialyzers during high-volume online hemodiafiltration-the comPERFORM study.

ABSTRACTBackgroundDialyzers should be designed to efficiently eliminate uraemic toxins during dialysis treatment, given that the accumulation of small and middle molecular weight uraemic solutes is associated with increased mortality risk of patients with end-stage renal disease. In the present study we investigated the novel FX CorAL dialyzer with a modified membrane surface for performance during online hemodiafiltration (HDF) in a clinical setting.MethodscomPERFORM was a prospective, open, controlled, multicentric, interventional, crossover study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online HDF to FX CorAL 600 (Fresenius Medical Care Deutschland), xevonta Hi 15 (B. Braun) and ELISIO 150H (Nipro) each for 1 week. The primary outcome was β2-m removal rate (β2-m RR) during online HDF. Secondary endpoints were RR and/or clearance of β2-m and other molecules. Albumin removal over time was an exploratory endpoint. Non-inferiority and superiority of FX CorAL 600 versus comparators were tested.ResultsFifty-two patients were included and analysed. FX CorAL 600 showed the highest β2-m RR (75.47%), followed by xevonta Hi 15 (74.01%) and ELISIO 150H (72.70%). Superiority to its comparators was statistically significant (P = 0.0216 and P < 0.0001, respectively). Secondary endpoints related to middle molecules affirmed these results. FX CorAL 600 demonstrated the lowest albumin removal up to 60 minutes and its sieving properties changed less over time than with comparators.ConclusionsFX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in β2-m RR. Albumin sieving kinetics point to reduced formation of a secondary membrane.

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.

High volume on line hemodiafiltration in dialysis pregnant patients: predilutional or postdilutional?

Although the frequency of pregnancy in women on chronic dialysis is extremely low, it is associated with severe maternal and perinatal morbidity and mortality. This situation represents a challenge for the therapeutic team, which requires multidisciplinary management, as well as measures to adequate dialysis treatment. Such efforts include increasing the time and frequency of dialysis session, maintaining low uremia levels and ensuring hemodynamic stability by avoiding intra-treatment arterial hypotension and hydro electrolytic fluctuations. Regarding the dialysis modality, literature makes references to hemodialysis or peritoneal dialysis in pregnancy women, but little is known about the of high volume online hemodiafiltration (HVHDF) as well as the appropriate type of replacement fluid (pre-dilution or post-dilution). We present two cases of patients who were pregnant while being treated with HVHDF modality and had a favorable evolution, where the decision to continue with this dialysis modality was motivated by a best hemodynamic stability and the highest clearance of all types of uremic toxins offered by HVHDF.

Effect of hemodiafiltration on measured physical activity: primary results of the HDFITrandomized controlled trial.

BackgroundDialysis patients are typically inactive and their physical activity (PA) decreases over time. Uremic toxicity has been suggested as a potential causal factor of low PA in dialysis patients. Post-dilution high-volume online hemodiafiltration (HDF) provides greater higher molecular weight removal and studies suggest better clinical/patient-reported outcomes compared with hemodialysis (HD).MethodsHDFIT was a randomized controlled trial at 13 clinics in Brazil that aimed to investigate the effects of HDF on measured PA (step counts) as a primary outcome. Stable HD patients (vintage 3–24 months) were randomized to receive HDF or high-flux HD. Treatment effect of HDF on the primary outcome from baseline to 3 and 6 months was estimated using a linear mixed-effects model.ResultsWe randomized 195 patients (HDF 97; HD 98) between August 2016 and October 2017. Despite the achievement of a high convective volume in the majority of sessions and a positive impact on solute removal, the treatment effect HDF on the primary outcome was +538 [95% confidence interval (CI) −330 to 1407] steps/24 h after dialysis compared with HD, and was not statistically significant. Despite a lack of statistical significance, the observed size of the treatment effect was modest and driven by steps taken between 1.5 and 24.0 h after dialysis, in particular between 20 and 24 h (+197 steps; 95% CI −95 to 488).ConclusionsHDF did not have a statistically significant treatment effect on PA 24 h following dialysis, albeit effect sizes may be clinically meaningful and deserve further investigation.

Effects of intradialytic cycling exercise on daily physical activity, physical fitness, body composition, and clinical parameters in high-volume online hemodiafiltration patients: a pilot randomized-controlled trial.

The mortality of dialysis patients treated with high-volume online hemodiafiltration (OL-HDF) is better than hemodialysis, but is still higher than healthy population. Low daily physical activity increases cardiovascular mortality. Addition of intradialytic exercise (IDX) program might improve physical activity and health status in OL-HDF patients. This pilot open-labeled randomized-controlled trial was conducted to evaluate the effects of IDX on physical activity and other clinical parameters in OL-HDF patients. Twelve OL-HDF patients were randomized into control (n = 6) or IDX (n = 6) groups. The subjects in IDX group were trained to exercise using a cycle ergometer for 60min during each OL-HDF session. Physical activity measured as daily step count using a wrist-worn triaxial accelerometer, physical fitness, or cardiorespiratory fitness assessed by VO2max and other physical performance tests, lean body mass determined by the Dual-energy X-ray absorptiometry (DXA), quality of life (QOL), and various parameters were compared between baseline and 6months. The baseline physical activity status was comparable. Following 6-month IDX, the physical activity was significantly improved in IDX group [+ 1048.79 (+ 741.50, + 2792.54) vs. -362.06 (-1626.82, -167.47) steps/day, p = 0.01], while physical fitness and QOL were unchanged. The lean body mass parameters were preserved in the IDX group while seemed to decrease in the control group. Serum albumin was significantly increased in the IDX group (p = 0.01). The hemoglobin changes were significantly better (p = 0.01) and the erythropoietin resistance index was significantly lower in the IDX group (p = 0.03). Phosphate reduction was significantly greater in the IDX group (p = 0.04). IDX could improve physical activity and other metabolic parameters in OL-HDF patients and these might contribute to further improvement in clinical and survival outcomes. ClinicalTrials.gov Registration: NCT03353844.

Achieving high convective volume in hemodiafiltration: Lessons learned after successful implementation in the HDFit trial.

High-volume online hemodiafiltration (OL-HDF) associates with improved outcomes compared to hemodialysis (HD), provided adequate dosing is achieved as estimated from convective volume (CV). Achievement of high CV and its impact on biochemical indicators following a standardized protocol converting HD patients to OL-HDF has not been systematically reported. We assessed the success of implementation of OL-HDF in clinics naïve to the modality. We analyzed the results of the implementation of postdilution OL-HDF in patients randomized to the HDF arm of a clinical trial (impact of hemoDiaFIlTration on physical activity and self-reported outcomes: a randomized controlled trial (HDFit) trial [ClinicalTrials.gov:NCT02787161]). The day before randomization of the first patient to OL-HDF at each clinic staff started a 3-day in-person training module on operation of Fresenius 5008 CorDiax machine in HDF mode. Patients were converted from high-flux HD to OL-HDF under oversight of trainers. OL-HDF was performed over a 6-months follow-up with a CV target of 22 L/treatment. We characterized median achieved CV >22 L/treatment record and analyzed the impact of HDF on biochemical variables. Ninety-seven patients (mean age 53 ± 16 years, 29% with diabetes, and 11% had a catheter) from 13 clinics randomized to the OL-HDF arm of the trial were converted from HD to HDF. Median CV > 22 L/treatment was achieved in 99% (94/95) of OL-HDF patients throughout follow-up. Monthly mean CV ranged from 27.1 L to 27.5 L. OL-HDF provided an increased single pool Kt/V at 3-months (0.2 [95% CI: 0.1-0.3]) and 6-months (0.2 [95% CI: 0.1-0.4]) compared to baseline, and reduced phosphate at 3-months (-0.4 mg/dL [95% CI: -0.8 to -0.12]) of follow-up. High-volume online hemodiafiltration was successfully implemented with 99% of patients achieving protocol defined CV target. Monthly mean CV was consistently >22 L/treatment during follow-up. Kt/V increased, and phosphate decreased with OL-HDF. Findings resulting from a short training period in several dialysis facilities appear to suggest HDF is an easily implementable technique.

Long-term effects of citric acid-based bicarbonate haemodialysis on patient outcomes: a survival propensity score-matched study in western France.

Citric acid-based bicarbonate haemodialysis (CIT-HD) has gained more clinical acceptance over the last few years in France and is a substitute for other acidifiers [e.g. acetic acid (CH3COOH) and hydrochloric acid (HCl)]. This trend was justified by several clinical benefits compared with CH3COOH as well as the desire to avoid the consequences of the corrosive action of HCl, but a nationwide clinical report raised concerns about the long-term safety of CIT-HD. The aim of this study was to assess the long-term effects of CIT-HD exposure on patient outcomes in western France. This is a population-based retrospective multicentre observational study performed in 1132 incident end-stage kidney disease patients in five sanitary territories in western France who started their renal replacement therapy after 1 January 2008 and followed up through 15 October 2018. Relevant data, collected prospectively with the same medical software, were anonymously aggregated for the purposes of the study. The primary goal of this study was to investigate the effects of citrate exposure on all-cause mortality. To provide a control group to CIT-HD one, propensity score matching (PSM) at 2:1 was performed in two steps: the first analysis was intended to be exploratory, comparing patients who received citrate ≤80% of the time (CIT-HD ≤80) versus those who received citrate >80% of the time (CIT-HD >80), while the second analysis was intended to be explanatory in comparing patients with 0% (CIT-HD0) versus 100% citrate time exposure (CIT-HD100). After PSM, in the exploratory part of the analysis, 432 CIT-HD ≤80 patients were compared with 216 CIT-HD >80 patients and no difference was found for all-cause mortality using the Kaplan-Meier model (log-rank 0.97), univariate Cox regression analysis {hazard ratio [HR] 1.01 [95% confidence interval (CI) 0.71-1.40]} and multivariate Cox regression analysis [HR 1.11 (95% CI 0.76-1.61)] when adjusted for nine variables with clinical pertinence and high statistical relevance in the univariate analysis. In the explanatory part of the analysis, 316 CIT-HD0 patients were then compared with 158 CIT-HD100 patients and no difference was found using the Kaplan-Meier model (log-rank 0.06), univariate Cox regression analysis [HR 0.69 (95% CI 0.47-1.03)] and multivariate Cox regression analysis [HR 0.87 (95% CI 0.57-1.33)] when adjusted for seven variables with clinical pertinence and high statistical relevance in the univariate analysis. Findings of this study support the notion that CIT-HD exposure ≤6 years has no significant effect on all-cause mortality in HD patients. This finding remains true for patients receiving high-volume online haemodiafiltration, a modality most frequently prescribed in this cohort.

Comparative Clinical Performance of Dialyzers Applied During High Volume Online Haemodiafiltration

Comparative Clinical Performance of Dialyzers Applied During High Volume Online Haemodiafiltration

Medium Cut-Off Dialyzer versus Eight Hemodiafiltration Dialyzers: Comparison Using a Global Removal Score

Background: A novel class of membranes, medium cut-off (MCO) membranes, has recently been designed to achieve interesting removal capacities for middle and large middle molecules in hemodialysis (HD) treatments. The few studies published to date have reported contradictory results regarding middle-sized molecules when comparing MCO dialyzers versus dialyzers used in online hemodiafiltration (OL-HDF). Methods: A prospective, single-center study was carried out in 22 patients. Each patient underwent 9 dialysis sessions with routine dialysis parameters, one with an MCO dialyzer in HD and the other 8 with different dialyzers in OL-HDF. The removal ratio (RR) of urea, creatinine, β₂-microglobulin, myoglobin, prolactin, α₁-microglobulin, α₁-acid glycoprotein, and albumin was intraindividually compared. Albumin loss in dialysate was measured. We propose a global removal score ([urea_RR + β₂-microglobulin_RR + myoglobin_RR + prolactin_RR + α₁-microglobulin_RR + α₁-acid glycoprotein_RR]/6 – albumin_RR) as a new tool for measuring dialyzer effectiveness. Results: No significant differences in the RRs of small and middle molecular range molecules were observed between the MCO vs. OL-HDF dialyzers (range 60–80%). Lower RRs were found for α₁-microglobulin and α₁-acid glycoprotein without significant differences. The albumin RR was < 11% and dialysate albumin loss was < 3.5 g in all situations without significant differences. The global removal score was 54.9 ± 4.8% with the MCO dialyzer without significant differences. Conclusions: Removal of a wide range of molecular weights, calculated with the proposed global removal score, was almost equal with the MCO dialyzer in HD treatment compared with 8 high-flux dialyzers in high-volume OL-HDF without relevant changes in albumin loss. The global removal score could be a new tool to evaluate the effectiveness of dialyzers and/or different treatment modalities.

Design and methodology of the impact of HemoDiaFIlTration on physical activity and self-reported outcomes: a randomized controlled trial (HDFIT trial) in Brazil

BackgroundEnd stage renal disease (ESRD) patients require a renal replacement therapy (RRT) to filter accumulated toxins and remove excess water, which are associated with impaired physical function. Hemodialysis (HD) removes middle-molecular weight (MMW) toxins less efficiently compared to hemodiafiltration (HDF); we hypothesized HDF may improve physical function. We detailed the design and methodology of the HDFIT protocol that is testing whether changing from HD to HDF effects physical activity levels and various outcomes.MethodsHDFIT is a prospective, multi-center, unblinded, randomized control trial (RCT) investigating the impact of dialysis modality (HDF verses HD) on objectively measured physical activity levels, self-reported quality of life, and clinical/non-clinical outcomes. Clinically stable patients with HD vintage of 3 to 24 months without any severe limitation ambulation were recruited from sites throughout southern Brazil. Eligible patients were randomized in a 1:1 ratio to either: 1) be treated with high volume online HDF for 6 months, or 2) continue being treated with high-flux HD. This study includes run-in and randomization visits (baseline), 3- and 6-month study visits during the interventional period, and a 12-month observational follow up. The primary outcome is the difference in the change in steps per 24 h on dialysis days from baseline to the 6-month follow up in patients treated with HDF versus HD. Physical activity is being measured over one week at study visits with the ActiGraph (www.actigraphcorp.com). For assessment of peridialytic differences during the dialysis recovery period, we will analyze granular physical activity levels based on the initiation time of HD on dialysis days, or concurrent times on non-dialysis days and the long interdialytic day.DiscussionIn this manuscript, we provide detailed information about the HDFIT study design and methodology. This trial will provide novel insights into peridialytic profiles of physical activity and various self-reported, clinical and laboratory outcomes in ESRD patients treated by high volume online HDF versus high-flux HD. Ultimately, this investigation will elucidate whether HDF is associated with patients having better vitality and quality of life, and less negative outcomes as compared to HD.Trial registrationRegistered on ClinicalTrials.gov on 20 April 2016 (NCT02787161).

Is High-Volume Online Hemodiafiltration Associated With Malnutrition?

Chronic malnutrition is a common problem in patients with end-stage renal disease on hemodialysis. Some studies have reported albumin loss into dialysis fluid during postdilution online hemodiafiltration (OL-HDF). The aim of the study was to assess the nutritional status of patients on high-volume OL-HDF and to demonstrate that higher convective clearances are not associated with malnutrition due to possible loss of nutrients with ultrafiltration. Demographic and clinical data, corporal composition with bioimpedance spectroscopy, dialysis features, albumin loss into dialysis fluid and laboratory parameters were collected in twenty-eight patients with ESRD undergoing postdilution OL-HDF with stable convective volumes over 28L/session. Convective volume (CV) in the last six months was 32.51±3.52L per session. Cross-sectional analysis of dialysis features showed 32.7±3.34L of CV and high reduction rates of beta-2-microglobulin (84.2±3.8%) and cystatin-C (81.6±3.47%). Beta-2-microglobulin reduction showed a positive correlation with prealbumin levels (P= 0.048). CV was only correlated with cystatin-C reduction (P=0.025). Estimated albumin loss into dialysis fluid (1.82±1.05 g/session) was not related to laboratory or bioimpedance nutritional parameters, or to CV. Among patients with higher CV, serum albumin levels maintained more stability during the observational period. High volume OL-HDF results in better convective clearances and is not associated with malnutrition. Albumin and nutrients loss into dialysis fluid should not be a limiting factor of the substitution volume.

Platelet activation and clotting cascade activation by dialyzers designed for high volume online hemodiafiltration.

Hemodialysis patients are pro-thrombotic. Higher volume online postdilutional hemodiafiltration (OL-HDF), with increasing hematocrit increases the risk of clotting in the extracorporeal circuit (ECC). We wished to determine whether OL-HDF increased platelet activation and ECC clotting. Coagulation parameters, platelet, white cell, and endothelial activation markers were measured at the start and end of dialysis sessions in 10 patients and also pre- and post-dialyzer after 15 minutes using two different dialyzers designed for high volume OL-HDF; cellulose triacetate (TAGP) and polysulphone (PS), and polyvinylpyrrolidone (PVP). Patients were anticoagulated with a heparin bolus. At the start of OL-HDF, D dimers, thrombin antithrombin complexes (TATs), and soluble adhesions molecules (sICAM-1 and sVCAM-1) were increased. Post-treatment soluble P selectin (PS/PVP 26.7 ± 7.1 versus 36.6 ± 9.9; TAGP 28.7 ± 7.2 versus 43.5 ± 8.4 ng/ml, P < 0.001), and soluble CD40 ligand (PS/PVP 297 ± 228 versus 552 ± 272, TAGP 245 ± 187 versus 390 ± 205 ng/ml, P < 0.05) increased. Post-dialyzer concentrations increased versus pre-dialyzer for tissue factor (PS/PVP 117 ± 12 versus 136 ± 16, TAGP 100 ± 25 versus 128 ± 40 ng/ml, P < 0.05), factor VIIIc (PS/PVP 174 ± 54 versus 237 ± 83, TAGP 163 ± 60 versus 247 ± 102 IU/ml, P < 0.01), sVCAM-1 (PS/PVP 782 ± 64 versus 918 ± 140, TAGP 722 ± 121 versus 889 ± 168 ng/ml, P < 0.01), and D-dimers (PS/PVP 292 ± 132 versus 355 ± 167, TAGP 300 ± 129 versus 391 ± 171 ng/ml, P < 0.001). There was no macroscopic thrombus noted in the ECC, and no increase in microparticles, platelet factor-4, or TATs. Despite being pro-thrombotic, with activation of platelets, and lymphocytes during passage through ECC, no macroscopic clotting, or increased TATs were noted during OL-HDF, and no major differences between cellulosic and polysulphone dialyzers.

New Biocompatible Haemodiafiltration Membrane to Enable Maximum Substitution for Sensitive Patients

In many European countries, high-volume online haemodiafiltration (OL-HDF) is becoming the method of choice for treating patients with chronic kidney disease. The high convective (Qs &gt;20 L/session) and diffusive properties of this treatment have been shown to be beneficial for patient survival. For optimum outcomes, the dialyser membrane must be able to cope with high transmembrane pressures. For this reason, the most widely-used membranes for this technique are synthetic and asymmetric in structure, making it easier for the membrane to divert the pressure away from its surface. However, patients allergic or sensitive to synthetic molecules, cannot access these high convective volumes (CV) reached in high-volume HDF, because alternative semi-natural membranes for allergic patients, such as cellulose acetate-based membranes, do not have adequate pressure-handling properties for high-volume HDF. At this symposium, a new type of cellulose triacetate (CTA)-based membrane that is biocompatible, able to perform high-volume OL-HDF, and suitable for sensitive patients was introduced.