Hemodiafiltration with endogenous reinfusion for uremic toxin removal in patients undergoing maintenance hemodialysis: a pilot study.

OBJECTIVE: To delineate the efficacy and safety profile of hemodiafiltration with endogenous reinfusion (HFR) for uremic toxin removal in patients undergoing maintenance hemodialysis (MHD). METHODS: Patients who have been on MHD for a period of at least 3 months were enrolled. Each subject underwent one HFR and one hemodiafiltration (HDF) treatment. Blood samples were collected before and after a single HFR or HDF treatment to test uremic toxin levels and to calculate clearance rate. The primary efficacy endpoint was to compare uremic toxin levels of indoxyl sulfate (IS), λ-free light chains (λFLC), and ß2-microglobulin (ß2-MG) before and after HFR treatment. Secondary efficacy endpoints was to compare the levels of urea, interleukin-6 (IL-6), P-cresol, chitinase-3-like protein 1 (YKL-40), leptin (LEP), hippuric acid (HPA), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), fibroblast growth factor 23 (FGF23) before and after HFR treatment. The study also undertook a comparative analysis of uremic toxin clearance between a single HFR and HDF treatment. Meanwhile, the lever of serum albumin and branched-chain amino acids before and after a single HFR or HDF treatment were compared. In terms of safety, the study was meticulous in recording vital signs and the incidence of adverse events throughout its duration. RESULTS: The study enrolled 20 patients. After a single HFR treatment, levels of IS, λFLC, ß2-MG, IL-6, P-cresol, YKL-40, LEP, HPA, TMAO, ADMA, TNF-α, and FGF23 significantly decreased (p < 0.001 for all). The clearance rates of λFLC, ß2-MG, IL-6, LEP, and TNF-α were significantly higher in HFR compared to HDF (p values: 0.036, 0.042, 0.041, 0.019, and 0.036, respectively). Compared with pre-HFR and post-HFR treatment, levels of serum albumin, valine, and isoleucine showed no significant difference (p > 0.05), while post-HDF, levels of serum albumin significantly decreased (p = 0.000). CONCLUSION: HFR treatment effectively eliminates uremic toxins from the bloodstream of patients undergoing MHD, especially protein-bound toxins and large middle-molecule toxins. Additionally, it retains essential physiological compounds like albumin and branched-chain amino acids, underscoring its commendable safety profile.

Hemodiafiltration: a synergy yet to be convincing.

The desperate attempt to improve mortality, morbidity, quality of life and patient-reported outcomes in patients on hemodialysis has led to multiple attempts to improve the different modes, frequencies, and durations of dialysis sessions in the last few decades. Nothing has been more appealing than the combination of diffusion and convection in the form of hemodiafiltration. Despite the concrete evidence of better clearance of middle weight molecules and better hemodynamic stability, tangible evidence to support the universal adoption is still at a distance. Survival benefits seen in selected groups who are likely to tolerate hemodiafiltration with better vascular access and with lower comorbid burden, need to be extended to real life dialysis patients who are older than the population studied and have significantly higher comorbid burden. Technical demands of initiation hemodiafiltration, the associated costs, and the incremental benefits targeted, along with patient-reported outcomes, need to be explored further before recommending hemodiafiltration as the mode of choice.

Effects of haemodiafiltration or haemofiltration compared with haemodialysis on prognosis in patients with end-stage renal disease: protocol an updated systematic review and meta-analysis of randomised trials with trial sequential analysis.

INTRODUCTION: Haemodialysis is the most common treatment option for patients with life-sustaining end-stage kidney disease (ESKD). In recent years, haemodiafiltration or haemofiltration has been widely used in patients with ESKD, and there are still conflicting findings as to whether both are superior to traditional haemodialysis. This systematic review and meta-analysis were designed to determine whether haemodiafiltration or haemofiltration is more effective than haemodialysis in reducing all-cause mortality risk in patients with ESKD. METHODS AND ANALYSIS: We will perform a systematic PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library and Scopus search, including studies published before September 2023. Randomised controlled trials will be included exploring the effects of haemodiafiltration or haemofiltration compared with haemodialysis on prognosis in patients with ESKD. Outcomes of interest include all-cause mortality, cardiovascular events, dialysis adequacy and adverse effects. The Cochrane Collaboration tools (ROB-2) will assess the bias risk. Available data will be used to calculate effect sizes. Heterogeneity between studies will be evaluated with I2. The trial sequential analysis will be used to eliminate false-positive results. The certainty of the evidence will be assessed using Grading of Recommendations, Assessment, Development and Evaluation criteria. ETHICS AND DISSEMINATION: This systematic review and meta-analysis was deemed exempt from ethics review. Results will be disseminated through publication in peer-reviewed journals and research conferences. PROSPERO REGISTRATION NUMBER: CRD42023464509.

The highlights of dialysis in 2023 / Les temps forts en dialyse en 2023

There has been a wealth of new developments in dialysis this year with the publication of several trials relating to dialysis technique, physical activity and the use of new dialysis treatments. Quality of life should be assessed and managed in all dialysis patients. Lowering the temperature of the dialysis bath in the MyTemp trial does not appear to have an effect on mortality and cardiovascular events. High volume convective hemodiafiltration currently represents the reference technique in hemodialysis; the Convince study confirms its superiority in terms of all-cause mortality. The DIATT study shows the benefit of the presence of an adapted physical activity professional to promote physical activity in dialysis patients and shows that it is necessary for this support to be reimbursed. The RENAL-AF and AXADIA-AFNET 8 studies lack power to conclude on the use of new oral anticoagulants in hemodialysis. For angiotensin receptor neprilysin inhibitors, studies are too weak to allow their use. SGLT2 inhibitors could be used in peritoneal dialysis to increase diuresis or delay the appearance of peritoneal fibrosis but to date only studies on models animals exist. Factor XI inhibitors are a new therapeutic class that could be used and would reduce the risk of thrombosis and hemorrhage. Increasingly, the feelings of patients and caregivers are more and more taken into account. Patient/caregiver communication must be at the heart of care. We will also be looking at the conservative treatment, the management of pruritus in hemodialysis and finally the care of patients with calciphylaxis.

Les nouveautés en dialyse ont été riches cette année avec la publication de plusieurs essais touchant aussi bien à la technique de dialyse, à l'activité physique et à l'utilisation de nouveaux traitements en dialyse. La qualité de vie doit être évaluée et prise en charge chez tous les patients dialysés. La baisse de température du bain de dialyse dans l'essai MyTemp ne semble pas avoir d'effet sur la mortalité et les événements cardiovasculaires. L'hémodiafiltration haut volume convectif représente la technique de référence en hémodialyse dialyse actuellement : l'étude Convince confirme sa supériorité en termes de mortalité toute cause. L'étude DIATT montre l'intérêt de la présence d'un professionnel en activité physique adaptée pour favoriser l'activité physique chez les patients dialysés et montre qu'il est nécessaire que cette prise en charge soit remboursée. Les études RENAL-AF et AXADIA-AFNET 8 manquent de puissance pour conclure sur l'utilisation des nouveaux anticoagulants oraux en hémodialyse. Pour les angiontensin receptor neprilysin inhibitor, les études sont trop faibles pour permettre leur utilisation. Les inhibiteurs des cotransporteurs sodium-glucose de type 2 (iSGLT2) pourraient être utilisés en dialyse péritonéale pour augmenter la diurèse ou retarder l'apparition de la fibrose péritonéale mais, à ce jour, seules des études sur modèles animaux existent. Les inhibiteurs du facteur XI sont une nouvelle classe thérapeutique qui pourrait être utilisée et diminuerait le risque de thrombose et d'hémorragie. Le ressenti des patients et aidants est de plus en plus pris en compte. La communication patients/soignants doit être au cœur de la prise en charge. Seront abordés également le traitement conservateur, la prise en charge du prurit en hémodialyse et le soin des patients atteints de calciphylaxie.

Is hemodiafiltration superior to high-flow hemodialysis in reducing all-cause and cardiovascular mortality in kidney failure patients? A meta-analysis of randomized controlled trials.

INTRODUCTION: Hemodiafiltration (HDF) and high-flux hemodialysis (hf-HD) are different methods of kidney replacement therapy (KRT) used for the treatment of kidney failure patients. A debate has raged over the last decade about the survival benefit of patients with the use of HDF compared with hf-HD, but with divergent results from randomized controlled trials. Therefore, this study aimed to perform a meta-analysis to compare HDF and hf-HD regarding all-cause and cardiovascular mortality. METHODS: PubMed and Cochrane databases were searched until July 19, 2023, for randomized clinical trials comparing HDF and hf-HD in patients on maintenance dialysis. A meta-analysis was performed using Stata 16.1, applying fixed or random effect models according to the heterogeneity between studies. FINDINGS: Of the 496 studies found, five met the inclusion criteria. Compared with the hf-HD group, the risk ratio (RR) for all-cause mortality with HDF use was 0.76 (95% CI: 0.67-0.88, I2 = 0%). HDF was associated with lower cardiovascular mortality, although the sensitivity analysis showed that the result differed between scenarios. Subgroup analysis showed lower all-cause mortality among patients without diabetes in the HDF group compared with hf-HD (RR 0.66, 95% CI: 0.51-0.81, I2 = 0%), but not in diabetic patients (RR = 0.89, 95% CI: 0.65-1.12, I2 = 0.0%). A subgroup analysis considering convection volumes was not performed, but the studies with the highest weight in the meta-analysis described convection volume as more than 20 L/session. DISCUSSION: More clinical studies considering critical risk factors, such as advanced age and preexisting cardiovascular disease, are needed to confirm the supremacy of HDF over hf-HD on the survival of patients treated by these two forms of kidney replacement therapy.

Controversy on the CONVINCE study findings: the PRO take.

The CONVINCE study, recently published in the New England Journal of Medicine, reveals a groundbreaking 23% reduction in the relative risk of all-cause mortality among end-stage kidney patients undergoing high convective volume hemodiafiltration. This significant finding challenges the conventional use of high-flux hemodialysis and offers hope for improving outcomes in chronic kidney disease patients. While some controversies surround the study's findings, including concerns about generalizability and the causes of death, it is essential to acknowledge the study's design and its main outcomes. The CONVINCE study, part of the HORIZON 2020 project, enrolled 1360 patients and demonstrated the superiority of hemodiafiltration in reducing all-cause mortality overall, as well as in specific patient subgroups (elderly, short vintage, non-diabetic, and those without cardiac issues). Interestingly, it was shown that hemodiafiltration had a protective effect against infection, including COVID-19. Future research will address sustainability, dose scaling effects, identification of subgroups especially likely to benefit and cost-effectiveness. However, for now, the findings strongly support a broader adoption of hemodiafiltration in renal replacement therapy, marking a significant advancement in the field.

[Clinical practice guideline for quality control of hemodiafiltration].

This guideline was co-authored by a writing committee of experts in hemodiafiltration. Based on the current evidence-based resources, the guideline drew on and referred to the current relevant clinical practice guidelines and expert recommendations at home and abroad, as well as the Standard Operating Procedures for Blood Purification (2021 Edition), focusing on clinical and medical quality control issues such as the indications for hemodiafiltration, the selection of treatment modes, the selection of replacement fluid and the adjustment of components, vascular access, anticoagulation therapy, prescription setting, and prevention and treatment of related complications. The guideline aimed to guide the clinical practice and clinical research of hemodiafiltration in China, and improve the standardization, normalization and homogeneity of medical quality of hemodiafiltration.

Clinical Efficacy and Long-term Prognosis of High Flux Hemodialysis Combined with Different Frequency Hemodiafiltration in the Treatment of Middle-Aged and Elderly Patients with Uremia.

INTRODUCTION: To analyze the clinical efficacy and long-term prognosis of high flux hemodialysis (HFHD) combined with different frequency hemodiafiltration (HDF) in uremic patients. METHODS: 86 middle-aged and elderly patients with uremia were divided into the HF group (HFHD combined with high-frequency HDF) and the LF group (HFHD combined with low-frequency HDF). The changes between the two groups in various indicators after 12 months of dialysis and the survival rate at 5 years of follow-up were compared. We used SPSS 25.0 software for data analysis. RESULTS: The differences of the levels of serum albumin, hemoglobin and transferrin in HF Group was significantly higher than LF Group before and after treatment (P < .05). The differences of the levels and clearance rate of calcium, phosphorus, parathyroid hormone, ß2-microglobulin and cysteine protease inhibitor C in the patients' blood after dialysis were significantly higher in HF Group than in LF Group (P < .05). The all-cause mortality rate, new cardiovascular event rate, new cerebrovascular event rate, and new infection event rate of HF Group were significantly lower than those of LFHD group, respectively (P < .05). The LF Group had a significantly higher risk of all-cause mortality events, new cardiovascular cerebrovascular and infectious events than the HF Group (P < .05). CONCLUSION: 1 week/time HDF combined with HFHD can more effectively eliminate the vascular related toxins in middle-aged and elderly patients with uremia, improve their nutritional status, treatment effect, and long-term prognosis.  DOI: 10.52547/ijkd.7864.

Successful treatment of a severe 5-hydroxytrytophan intoxication using carbon hemoperfusion, hemodiafiltration, and mechanical ventilation in a dog.

OBJECTIVE: To describe the successful use of carbon hemoperfusion and hemodiafiltration in combination with mechanical ventilation (MV) to treat a severe intoxication of 5-hydroxytryptophan (5-HTP) in a dog. CASE SUMMARY: A dog ingested a minimum of 550 mg/kg of extended-release 5-HTP, resulting in serotonin syndrome that progressed to a comatose state and severe hypoventilation requiring MV. Extracorporeal carbon hemoperfusion coupled with hemodiafiltration was performed to remove 5-HTP from this patient. A carbon hemoperfusion cartridge was placed in series upstream in the extracorporeal circuit from the hemodialyzer. A total of 46.5 L of blood (4.89 L/kg) was processed during a 4.85-hour treatment. Serial plasma samples were obtained at 0, 60, 90, and 150 minutes during the session and 14 hours after the session. These samples were later analyzed for 5-HTP and serotonin concentrations. The extraction ratio of 5-HTP was 93.6%-98.9% through the carbon filter. The dog was weaned from MV within 8 hours after extracorporeal therapy and, after a full recovery, was successfully discharged. NEW OR UNIQUE INFORMATION PROVIDED: Despite an extensive review of the available literature, this appears to be the first reported case of using a carbon hemoperfusion, hemodiafiltration, and MV to treat severe serotonin syndrome secondary to 5-HTP intoxication in a dog. The combination of carbon hemoperfusion and hemodiafiltration can significantly reduce plasma 5-HTP concentrations after acute intoxication and may serve to decrease morbidity and mortality in patients with severe intoxication.

Comparison of citrate dialysate in pre- and post-dilution online hemodiafiltration: effect on clot formation and adequacy of dialysis in hemodialysis patients.

BACKGROUND: Citrate dialysate (CD) has been successfully used in conventional hemodialysis and continuous renal replacement therapy; however, no study has compared pre- and post-dilution online hemodiafiltration (oL-HDF). Therefore, we aimed to investigate the efficacy of citrate anticoagulation for oL-HDF and the metabolic changes and quality of life of patients on hemodialysis treated using both modes. METHOD: Eight dialysis patients were treated with CD containing 0.8 mmol of citric acid for 4 weeks in each phase. Visual clotting scores were investigated as the primary endpoints. Adequacy of dialysis, laboratory parameters, and quality of life were measured as secondary objectives. RESULTS: The mean clotting scores in the pre-dilution mode were significantly lower than those in the post-dilution mode and in all phases except the heparin-free phase (p < 0.001 in the baseline phase, p = 0.001 in phase 1, and p = 0.023 in phase 2). The values of Kt/V in both modalities were comparable except during the baseline phase, in which the values of pre-dilution were significantly greater than post-dilution (2.36 ± 0.52/week vs. 1.87 ± 0.33/week;95% CI -0.81 to -0.19, p = 0.002). The patient's quality of life regarding their physical activity level was significantly higher in the post-dilution mode than in the pre-dilution mode at baseline and in phase 1 (p = 0.014 and 0.004 at baseline and in phase 1, respectively). Metabolic changes did not differ between the two modes. CONCLUSION: Citrate dialysate decreased or prevented anticoagulation in both pre- and post-dilution modes of oL-HDF without significant side effects and had comparable adequacy of dialysis.

Anti-inflammatory effect of high flux dialyzer surface area 2.6m2 in high flux hemodialysis and hemodiafiltration.

Dialysis therapy has remarkably evolved through the innovation in dialyzers and hemodialysis modalities, enhancing patients' quality of life. The efficacy of dialysis can be determined by measuring the reduction ratio (RR) of middle molecules such as Interleukin-6 (IL-6) and Procalcitonin. In our study, we tested a high-flux dialyzer, BIOPURE (Biorema) 260 HF, with a surface area (SA) of 2.6 m2, in terms of IL-6 and Procalcitonin removal while performing high-flux hemodialysis (HF-HD) and post-dilution online hemodiafiltration (OL-HDF). This crossover study comprised 25 patients who received a session of HF-HD using the BIOPURE (Biorema) 260 H, followed by a session of post-dilution OL-HDF. A washout period of 2 weeks was instilled between the two sessions, during which the patients received HF-HD using high-flux dialyzers (maximum SA 2.0 m2). All patients' pre/post dialysis concentrations of IL-6 and procalcitonin were measured. The dialyzer used in this study resulted in a significant IL-6 RR of 44.92±5.11% (p <0.001) with HDF and 32.48±5.72% (p <0.001) with HF-HD; and a procalcitonin RR of 50.32±3.94% (p <0.001) with HDF and 41.80±4.32% (p <0.001) with HF-HD. In conclusion, the dialyzer BIOPURE (Biorema) 260 HF (SA 2.6 m2) is efficient in eliminating IL-6 and procalcitonin, especially with OL-HDF compared to HF-HD, with acceptable albumin loss in the dialysate.

Comparison of the pre-dilution and post-dilution methods for online hemodiafiltration.

Online hemodiafiltration (OL-HDF) is a treatment modality using diffusion and ultrafiltration. There are two types of dilution methods in OL-HDF: pre-dilution, which is commonly provided in Japan, and post-dilution, which is commonly provided in Europe. The optimal OL-HDF method for individual patients is not well studied. In this study, we compared the clinical symptoms, laboratory data, spent dialysate, and adverse events of pre- and post-dilution OL-HDF. We conducted a prospective study of 20 patients who underwent OL-HDF between January 1, 2019 and October 30, 2019. Their clinical symptoms and dialysis efficacy were evaluated. All patients underwent OL-HDF every 3 months in the following sequence: first pre-dilution, post-dilution, and second pre-dilution. We evaluated 18 patients for the clinical study and 6 for the spent dialysate study. No significant differences in spent dialysates regarding small and large solutes, blood pressure, recovery time, and clinical symptoms were observed between the pre- and post-dilution methods. However, the serum α1-microglobulin level in post-dilution OL-HDF was lower than that in pre-dilution OL-HDF (first pre-dilution: 124.8 ± 14.3 mg/L; post-dilution: 116.6 ± 13.9 mg/L; second pre-dilution: 125.8 ± 13.0 mg/L; first pre-dilution vs. post-dilution, post-dilution vs. second pre-dilution, and first pre-dilution vs. second pre-dilution: p = 0.001, p < 0.001, and p = 1.000, respectively). The most common adverse event was an increase in transmembrane pressure in the post-dilution period. Compared to pre-dilution, the post-dilution method decreased the α1-microglobulin level; however, there were no significant differences in clinical symptoms or laboratory data.

An evaluation of different dilution modes on circuit lifespan during continuous veno-venous hemodiafiltration without anticoagulation.

BACKGROUND: Circuit clotting remains a major problem during continuous kidney replacement therapy (CKRT), particularly in patients with contraindications to anticoagulant use. We hypothesized that the different options of alternative replacement fluid infusion sites might affect circuit lifespan. However, research-based evidence supporting an optimal replacement fluid infusion strategy is limited. Therefore, we aimed to evaluate the effect of three dilution modes (pre-dilution, post-dilution, and pre- to post-dilution) on circuit lifespan during continuous veno-venous hemodiafiltration (CVVHDF). METHODS: This prospective cohort study was conducted between December 2019 and December 2020. Patients requiring CKRT were enrolled to receive pre-dilution, post-dilution, or pre- to post-dilution fluid infusion with CVVHDF. The primary endpoint was circuit lifespan, and the secondary outcomes included the clinical parameters of patients, such as changes in serum creatinine (Scr) and blood urea nitrogen (BUN) levels, 28-day all-cause mortality, and length of stay. For all patients included in this study, only the first circuit used was recorded. RESULTS: Among the 132 patients enrolled in this study, 40 were in the pre-dilution mode, 42 were in the post-dilution mode, and 50 were in the pre- to post-dilution mode. The mean circuit lifespan was significantly longer in the pre- to post-dilution group (45.72 h, 95% CI, 39.75-51.69 h) than in the pre-dilution group (31.58 h, 95% CI, 26.33-36.82 h) and the post-dilution group (35.20 h, 95% CI, 29.62-40.78 h). There was no significant difference between the pre- and post-dilution group circuit lifespan (p > 0.05). Kaplan-Meier survival analysis revealed a significant difference between the three dilution modes (p = 0.001). No significant differences were observed in terms of changes in the Scr and BUN levels, admission day, and 28-day all-cause mortality among the three dilution groups (p > 0.05). CONCLUSION: The pre- to post-dilution mode significantly prolonged circuit lifespan but did not reduce Scr and BUN levels, compared with the pre-dilution and post-dilution modes during CVVHDF when no anticoagulants were used.

Do patients dialysing with higher ultrafiltration rates report more intradialytic symptoms and longer postdialysis recovery times?

BACKGROUND: Many hemodialysis (HD) patients report intradialytic symptoms, and take time to recover postdialysis. To improve quality of life, patient groups have highlighted the need to reduce postdialysis fatigue and other peridialytic symptoms. As compartmental shifts of fluid during dialysis have been proposed to cause peridialytic symptoms we investigated whether patients dialysing with higher ultrafiltration rates (UFR) reported more intradialytic symptoms and recovery times. METHODS: We reviewed the hospital records of HD patients who completed a self-reported intradialytic symptom questionnaire, using a visual analogue scale, who had contemporaneous midweek pre- and postdialysis segmental bioimpedance measurements. RESULTS: Six hundred and five patients returned the peridialytic symptom questionnaire with pre- and postdialysis bioimpedance measurements. The majority were male (64.8%), mean age 64.2 ± 15.6 years, duration of dialysis treatment 26.8 (10.7-59.2) months, 85% treated by hemodiafiltration and mean dialysate temperature 35.4 ± 0.4°C. We divided patients into terciles according to UFR adjusted for weight, and there was a greater fall in the ratio of extracellular water (ECW) to total body water (TBW) postdialysis in the nonfistula arm from the lower to middle to higher tercile (0.8 (0-1.54) vs. 1.28 (0.52-1.85) vs. 1.54 (0.78-2.52)), trunk (1.5 (0.74-2.27) vs. 1.53 (0.99-2.2) vs. 1.98 (1.18-2.66)), left leg (1.56 (0.49-2.25) vs. 1.77 (1.24-2.43) vs. 2.08 (1.18-2.95)), lower versus higher tercile p < 0.05. However, no differences in intradialytic symptoms or postdialysis recovery times between the UFR terciles were observed. CONCLUSION: There were no differences in self-reported intradialytic symptoms or postdialysis recovery times with differing UFRs, despite changes in intracompartmental fluid shifts as measured by changes in ECW/TBW.

A pilot study of intensive short-time continuous renal replacement therapy to substitute maintenance hemodialysis during transitional period of COVID-19.

INTRODUCTION: There is a lack of perfect solutions for maintenance hemodialysis (MHD) in patients with a high transmission risk of SARS-CoV-2. METHODS: MHD patients with a high risk of SARS-CoV-2 transmission from April 1 to June 30, 2022, were recruited. We performed 4-h continuous renal replacement therapy with Prismaflex dialysis machine and ST100 suite using continuous venovenous hemodiafiltration (CVVHDF) mode with a fluid exchange volume of 8000 mL/h. RESULTS: Forty-five MHD patients were included with a median dialysis age of 91 months. Overall spKt/V reached 0.96 ± 0.19. Urea reduction ratio was 50.29 ± 7.60% with the ultrafiltration of 2.18 ± 0.79 kg. Dry weight was significantly inversely correlated with spKt/V (R = -0.563, p < 0.001). Female gender was a significant positive factor of spKt/V. Preheating of replacement solution using an incubator solved the complication of shivering in most patients. CONCLUSION: Intensive short-time CVVHDF may be considered as an alternative for routine MHD during COVID-19 transitional period.

Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study.

INTRODUCTION: The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α1-Microglobulin (α1-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α1-m and ß2-microglobulin (ß2-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in comparison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study. METHODS: Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α1-m, ß2-m, small molecules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment. RESULTS: Clearance rates of α1-m at 60 min were -2.8 ± 5.2 mL/min with Pre-PS, -0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α1-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of ß2-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS. CONCLUSION: The removal rate of α1-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed ß2-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effectively removes α1-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.

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.

Extracorporeal Techniques in Kidney Failure.

During the last decades, various strategies have been optimized to enhance clearance of a variable spectrum of retained molecules to ensure hemodynamic tolerance to fluid removal and improve long-term survival in patients affected by kidney failure. Treatment effects are the result of the interaction of individual patient characteristics with device characteristics and treatment prescription. Historically, the nephrology community aimed to provide adequate treatment, along with the best possible quality of life and outcomes. In this article, we analyzed blood purification techniques that have been developed with their different characteristics.