Comparative analyses of adsorbed circulating proteins in the PMMA and PES hemodiafilters in patients on predilution online hemodiafiltration.

Acute and chronic inflammation are common in patients with end-stage kidney disease (ESKD). So, the adsorption of pro-inflammatory cytokines by the hollow fiber of the dialysis membrane has been expected to modify the inflammatory dysregulation in ESKD patients. However, it remains to be determined in detail what molecules of fiber materials can preferably adsorb proteins from the circulating circuit. We aimed this study to analyze directly the adsorbed proteins in the polymethyl methacrylate (PMMA) and polyethersulfone (PES) membranes in patients on predilution online hemodiafiltration (OL-HDF). To compare the adsorbed proteins in the PMMA and PES hemodiafilters membrane, we initially performed predilution OL-HDF using the PES (MFX-25Seco) membrane while then switched to the PMMA (PMF™-A) membrane under the same condition in three patients. We extracted proteins from the collected hemodiafilters by extraction, then SDS-PAGE of the extracted sample, protein isolation, in-gel tryptic digestion, and nano-LC MS/MS analyses. The concentrations of adsorbed proteins from the PMMA and PES membrane extracts were 35.6±7.9 µg/µL and 26.1±9.2 µg/µL. SDS-PAGE analysis revealed distinct variations of adsorbed proteins mainly in the molecular weight between 10 to 25 kDa. By tryptic gel digestion and mass spectrometric analysis, the PMMA membrane exhibited higher adsorptions of ß2 microglobulin, dermcidin, retinol-binding protein-4, and lambda-1 light chain than those from the PES membrane. In contrast, amyloid A-1 protein was adsorbed more potently in the PES membrane. Western blot analyses revealed that the PMMA membrane adsorbed interleukin-6 (IL-6) approximately 5 to 118 times compared to the PES membrane. These findings suggest that PMMA-based OL-HDF therapy may be useful in controlling inflammatory status in ESKD patients.

Randomized investigation of increased dialyzer membrane hydrophilicity on hemocompatibility and performance.

BACKGROUND: Hemodialyzers should efficiently eliminate small and middle molecular uremic toxins and possess exceptional hemocompatibility to improve well-being of patients with end-stage kidney disease. However, performance and hemocompatibility get compromised during treatment due to adsorption of plasma proteins to the dialyzer membrane. Increased membrane hydrophilicity reduces protein adsorption to the membrane and was implemented in the novel FX CorAL dialyzer. The present randomized controlled trial compares performance and hemocompatibility profiles of the FX CorAL dialyzer to other commonly used dialyzers applied in hemodiafiltration treatments. METHODS: This prospective, open, controlled, multicentric, interventional, crossover study randomized stable patients on post-dilution online hemodiafiltration (HDF) to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun) each for 4 weeks. Primary outcome was ß2-microglobulin removal rate (ß2-m RR). Non-inferiority and superiority of FX CorAL versus comparators were tested. Secondary endpoints were RR and/or clearance of small and middle molecules, and intra- and interdialytic profiles of hemocompatibility markers, with regards to complement activation, cell activation/inflammation, platelet activation and oxidative stress. Further endpoints were patient reported outcomes (PROs) and clinical safety. RESULTS: 82 patients were included and 76 analyzed as intention-to-treat (ITT) population. FX CorAL showed the highest ß2-m RR (76.28%), followed by FX CorDiax (75.69%) and xevonta (74.48%). Non-inferiority to both comparators and superiority to xevonta were statistically significant. Secondary endpoints related to middle molecules corroborated these results; performance for small molecules was comparable between dialyzers. Regarding intradialytic hemocompatibility, FX CorAL showed lower complement, white blood cell, and platelet activation. There were no differences in interdialytic hemocompatibility, PROs, or clinical safety. CONCLUSIONS: The novel FX CorAL with increased membrane hydrophilicity showed strong performance and a favorable hemocompatibility profile as compared to other commonly used dialyzers in clinical practice. Further long-term investigations should examine whether the benefits of FX CorAL will translate into improved cardiovascular and mortality endpoints. TRIAL REGISTRATION: eMPORA III registration on 19/01/2021 at ClinicalTrials.gov (NCT04714281).

Dengue rhabdomyolysis successfully treated with hemoperfusion using CytoSorb® in combination with continuous renal replacement therapy: a case report.

BACKGROUND: Dengue fever is a mosquito-borne viral infection with a broad spectrum of clinical manifestations. Expanded dengue syndrome includes unusual manifestations that do not fall into the categories of dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Rhabdomyolysis causing acute renal failure in dengue is one such unusual manifestation, the pathophysiology of which is incompletely understood. CASE PRESENTATION: We describe a 21-year-old Sri Lankan man with dengue fever who developed severe rhabdomyolysis and acute kidney injury with extremely high creatinine phosphokinase levels (> 2 million U/L). Management of this patient was challenging as his creatinine phosphokinase kept rising with persistent anuria despite hydration, intermittent hemodialysis, and, later, continuous venovenous hemodiafiltration. Further therapeutic options were explored, and CytoSorb® adsorber was added as an adjunct to continuous venovenous hemodiafiltration, following which we observed a marked reduction in his creatinine phosphokinase and myoglobin levels over the next 12 hours and complete renal recovery over the next 5 weeks. CONCLUSION: We report a rare case of significant rhabdomyolysis secondary to dengue infection leading to acute kidney injury. Continuous venovenous hemodiafiltration performed with the hemofilter Pecopen 140 was ineffective, and the addition of CytoSorb® adsorber as an adjunct therapy to continuous venovenous hemodiafiltration may have a potential benefit in removing high-molecular-weight proteins such as myoglobin.

Contribution of Adsorption and Hematocrit Levels to Ganciclovir Clearance in an in Vitro Continuous Hemodiafiltration Model.

Estimation of the continuous hemodiafiltration (CHDF) clearance (CLCHDF) of ganciclovir (GCV) is crucial for achieving efficient treatment outcomes. Here, we aimed to clarify the contribution of diafiltration, adsorption, and hematocrit level to the CLCHDF of GCV in an in vitro CHDF model using three membranes: polyacrylonitrile and sodium methallyl sulfonate copolymer coated with polyethylenimine (AN69ST); polymethylmethacrylate (PMMA); and polysulfone (PS). In vitro CHDF was performed with effluent flow rates (Qe) of 800, 1500, and 3000 mL/h. The initial GCV concentration was 10 µg/mL while that of human serum albumin (HSA) was 0 or 5 g/dL. The CLCHDF, diafiltration rates, and adsorption rates were calculated. The whole blood-to-plasma ratio (R) of GCV for a hematocrit of 0.1 to 0.5 was determined using blood samples with 0.5 to 100 µg/mL of GCV. The in vitro CHDF experiment using AN69ST, PMMA, and PS membranes showed that the total CLCHDF values were almost the same as the Qe and not influenced by the HSA concentration. The diafiltration rate exceeded 88.1 ± 2.8% while the adsorption rate was lower than 9.4 ± 9.4% in all conditions. The R value was 1.89 ± 0.11 and was similar at all hematocrit levels and GCV concentrations. In conclusion, diafiltration mainly contributes to the CLCHDF of GCV, rather than adsorption. Hematocrit levels might not affect the relationship between the plasma and blood CLCHDF of GCV, and the CLCHDF of GCV can be estimated from the Qe and R, at least in vitro.

[Primary renal triple expressor DLBCL treated with chemotherapy under continuous hemodialysis and filtration support].

A 69-year-old woman was previously treated with antibiotics for suspected pyelonephritis due to fever but showed limited improvement. Contrast-enhanced CT revealed heterogeneous areas of decreased contrast enhancement in both kidneys, along with an elevated soluble level of the IL-2 receptor (5,090 U/ml), and thus the patient was referred to our department for further evaluation. A percutaneous renal biopsy performed due to suspected malignant lymphoma confirmed lymphoma cell infiltration into the renal interstitium. Immunohistochemical staining was positive for MYC/BCL2/BCL6, leading to the diagnosis of stage IVB primary renal triple expressor diffuse large B cell lymphoma (DLBCL). Due to acute kidney injury, continuous hemodiafiltration (CHDF) was initiated, followed by rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. The patient's renal function improved rapidly, and complete response was achieved after six cycles of R-CHOP. Although DLBCL is a common lymphoma, the primary renal subtype is extremely rare and poses both diagnostic and therapeutic challenges. This case highlights the potential clinical implications of combining CHDF with chemotherapy to achieve complete response despite an initial poor prognosis based on the patient's overall clinical condition and pathology.

Calcium mass balance in adults during single hemodialysis and hemodiafiltration treatments using lower calcium dialysate concentrations.

BACKGROUND: Debate continues as to the optimum hemodialysis (HD) dialysate calcium concentration. Although current guidelines advocate 1.25-1.5 mmol/L, some investigators have suggested these may cause calcium gains. As such we investigated whether using dialysate calcium of 1.25 mmol/L risked calcium gains, and whether there were differences between hemodiafiltration and high flux HD. METHODS: We continuously collect an aliquot of effluent dialysate during dialysis sessions, and calculated dialysis calcium mass balance by the difference between the amount of calcium delivered as fresh dialysate and that lost in effluent dialysate. RESULTS: We studied 106 stable outpatients, 64% male, mean age 64.4 ± 16.2 years, median dialysis vintage 32 (22-60) months. Most sessions (69%) used a 1.0 mmol/L calcium dialysate, with a median sessional loss of 13.7 (11.5-17.1) mmol, whereas using 1.25 mmol/L the median loss was 7.4 (4.9-10.1) mmol, but with 6.9% had a positive balance (p = 0.031 vs dialysate calcium 1.0 mmol/L). Most patients (85.8%) were treated by hemodiafiltration, but there was no difference in sessional losses (11.7 (8.4-15.8) vs 13.5 (8.1-16.8)) with high flux HD. Dialysis sessional calcium balance was associated with the use of lower dialysate calcium concentration (ß -19.5, 95% confidence limits (95%CL) -27.7 to -11.3, p < 0.001), and sessional duration (ß 0.07 (95% CL) 0.03-012, p = 0.002). CONCLUSION: Ideally, the choice of dialysate calcium should be individualized, but clinicians should be aware, that even when using a dialysate calcium of 1.25 mmol/L, some patients are at risk of a calcium gain during hemodiafiltration and high-flux hemodialysis.

A chronic intermittent haemodialysis pig model for functional evaluation of dialysis membranes.

Performance evaluation of new dialysis membranes is primarily performed in vitro, which can lead to differences in clinical results. Currently, data on dialysis membrane performance and safety are available only for haemodialysis patients. Herein, we aimed to establish an in vivo animal model of dialysis that could be extrapolated to humans. We created a bilateral nephrectomy pig model of renal failure, which placed a double-lumen catheter with the hub exposed dorsally. Haemodialysis was performed in the same manner as in humans, during which clinically relevant physiologic data were evaluated. Next, to evaluate the utility of this model, the biocompatibility of two kinds of membranes coated with or without vitamin E used in haemodiafiltration therapy were compared. Haemodialysis treatment was successfully performed in nephrectomized pigs under the same dialysis conditions (4 h per session, every other day, for 2 weeks). In accordance with human clinical data, regular dialysis alleviated renal failure in pigs. The vitamin E-coated membrane showed a significant reduction rate of advanced oxidation protein products during dialysis than non-coated membrane. In conclusion, this model mimics the pathophysiology and dialysis condition of patients undergoing haemodialysis. This dialysis treatment model of renal failure will be useful for evaluating the performance and safety of dialysis membranes.

Comparison of efficacy and safety of the new generation helixone dialyzers.

INTRODUCTION: New generation helixone dialyzers has recently been developed as part of the ongoing effort to improve dialyzer hemocompatibility and avoid adverse reactions to synthetic dialyzers. This study aimed to assess the performance and albumin loss of this new dialyzer series in hemodiafiltration and compare it with the previous generation helixone series. MATERIAL AND METHODS: A prospective study was conducted in 19 patients. Each patient underwent eight dialysis sessions with the same routine dialysis parameters; only the dialyzer varied: FX60 CorDiax, FX CorAL 60, FX600 CorDiax, FX CorAL 600, FX80 CorDiax, FX CorAL 80, FX800 CorDiax, and FX CorAL 800. The reduction ratios (RR) of urea, creatinine, ß2-microglobulin, myoglobin, kappa-free immunoglobulin light chains (κFLC), prolactin, α1-microglobulin, α1-acid glycoprotein, lambda immunoglobulin light chains (λFLC), and albumin were compared intra-individually. Dialysate albumin loss was also measured. RESULTS: All treatments were well tolerated. The mean amount of replacement fluid ranged from 31 to 34 L. Comparison of dialysis treatments showed no differences between small molecules and even up to those the size of ß2-microglobulins. Little differences were found between myoglobin, κFLC, prolactin, α1-microglobulin, and λFLC RRs, and only FX80 CorDiax was slightly superior to the others. Mean dialysate albumin losses were similar, with less than 2.5 g lost in each dialyzer. The FX80 CorDiax showed slightly higher global removal scores than the other dialyzers evaluated, except for FX CorAL 800. CONCLUSION: The new generation helixone dialyzers series has been updated to minimise the risk of adverse reactions, while maintaining the effectiveness and albumin loss achieved by the previous most advanced helixone generation.

Relationship between effective blood flow rate and clinical outcomes in maintenance hemodialysis patients: a single-center study.

The association between blood flow rate (BFR) and clinical outcomes in patients undergoing maintenance hemodialysis (MHD) is inconclusive. This retrospective study included 175 patients undergoing MHD treatment between July 2015 and March 2022, divided into two groups based on time-averaged effective blood flow rate (eBFR) median value. We investigated arteriovenous fistula (AVF) outcomes and the association of eBFR with all-cause mortality and new major adverse cardiovascular events (MACE). Mean ± SD and median time-averaged eBFR values were 276 ± 24 and 275 mL/min, respectively. After adjusting for relevant factors including age, sex, vintage, diabetes, CVD, receiving hemodiafiltration (HDF) treatment and spKt/V, Cox models indicated a low time-averaged eBFR (≤ 275 ml/min) was associated with increased risks of all-cause mortality (hazard ratio [HR] 14.18; 95% confidence interval [CI], 3.14-64.1) and new MACE (HR 3.76; 95% CI, 1.91-7.40) in MHD patients. Continuous Cox models demonstrated each 20 ml/min increase in eBFR linked to a 63% decrease in the risk of all-cause mortality (HR: 0.37, 95% CI: 0.23-0.59) and a 38% decrease in the occurrence of new MACE (HR: 0.62, 95% CI: 0.46-0.84). There was no significant difference in AVF outcomes between the two groups. Our study noted higher eBFR (>275 mL/min) is associated with lower risks of both all-cause mortality and new MACE compared with low eBFR (≤275 mL/min). Increased eBFR is not associated with a higher risk of AVF failure.

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.

Experience with Tandem Pre-Dilution Online Hemodiafiltration and Centrifugal Plasma Exchange in Pretransplant Desensitization for Abo-Incompatible Kidney Transplantation: A Case Report.

BACKGROUND: In the use of therapeutic plasma exchange (TPE) as antibody removal therapy for ABO-incompatible (ABOi) kidney transplantation, it is technically possible to perform online hemodiafiltration (OHDF) and TPE simultaneously for patients who are receiving OHDF. In this study, we report tandem therapy of pre-dilution OHDF and centrifugal plasma exchange (cTPE), instead of membrane plasma exchange, which is the mainstay of TPE in Japan. METHODS: A total of 14 sessions of tandem cTPE and pre-dilution OHDF were performed as preoperative antibody removal therapy for 6 ABOi kidney transplant recipients. cTPE intra-circuit pressure, decreased antibody titer, and adverse events were evaluated. The study was carried out following the ethical standards of the Declaration of Helsinki and Istanbul. Donors were not prisoners or individuals who were coerced or paid. RESULTS: The tandem therapy was completed safely in 12 of the 14 sessions, with no problems such as pressure upper and lower limit alarms or circuit coagulation. In 2 sessions, the tandem therapy had to be interrupted due to coagulation on the dialysis circuit side. Antibody titers were reduced by a median of 3-fold for both IgG and IgM. There was no acute antibody-associated rejection. CONCLUSIONS: In preoperative apheresis therapy for ABOi kidney transplantation, tandem therapy of pre-dilution OHDF and cTPE may be a useful treatment option that can be performed safely and results in sufficient reduction of antibody levels.

Removal of inflammatory factors and prognosis of patients with septic shock complicated with acute kidney injury by hemodiafiltration combined with HA330-II hemoperfusion.

INTRODUCTION: To explore the effect of CRRT using CVVHDF + HP on the removal of inflammatory mediators in patients with septic shock complicated with AKI. METHODS: A total of 20 patients between January 1, 2018, and December 31, 2021, were included. The patients were randomly divided into the treatment group (CVVHDF + HP) and the control group (CVVHDF). Changes in inflammatory factors, including IL-1ß, IL-6, IL-8, TNF-α, PCT, and CRP were compared. Other observed measures were also analyzed, for example, Lac, Scr, BUN, SOFA, and norepinephrine (NE) dosage. The clinical outcomes of both groups were followed up for 28 days. RESULTS: The IL-6 and PCT levels in the treatment group were significantly lower (p = 0.005, 0.007). Although the IL-1ß, TNFα, and CRP levels in the treatment group decreased, there were no statistical differences (p > 0.05). There were significant differences in Lac, SOFA, and NE dosage levels between both groups (p = 0.023, 0.01, 0.023). Survival analysis showed that the 28-day survival rate was significantly higher in the treatment group. CONCLUSION: CRRT using CVVHDF+HP can effectively remove inflammatory factors and improve the prognosis of patients.

Most recently developed polyester polymer alloy dialyzer: A new medium cut-off membrane?

BACKGROUND: New versions of the polyester polymer alloy (PEPA) membrane have appeared over the years, with increases in both the pore size and the amount of polyvinylpyrrolidone (PVP) to optimize hydrophilicity performance. This study aimed to assess the efficacy of the most recently developed PEPA dialyzer, the FDY series, in hemodialysis (HD) modality in terms of uremic toxin removal and albumin loss and to compare it with that of several high-flux dialyzers currently used in HD and post-dilution hemodiafiltration (HDF) treatments. METHODS: A prospective study was carried out in 21 patients. All patients underwent six dialysis sessions with the same routine dialysis parameters; only the dialyzer and/or the dialysis modality varied: FX80 in HD, FDY 180 in HD, Clearum HS17 in HDF, Elisio 19H in HDF, Vitapes 180 in HDF, and FX80 in post-dilution HDF. The reduction ratios (RR) of urea, creatinine, ß2-microglobulin, myoglobin, κFLC, prolactin, α1-microglobulin, α1-acid glycoprotein, λFLC, and albumin were compared intraindividually. Dialysate albumin loss was also measured. RESULTS: Both membranes FDY and FX80 are high-flux dialyzers and are applied here in high-flux HD. The average RR of ß2-microglobulin was slightly lower in the two HD treatments than in the HDF treatments. Comparison of dialysis treatments revealed that the PEPA FDY dialyzer in the HD modality was more effective than the FX80 dialyzer in high-flux HD and was as effective as post-dilution HDF, especially in terms of myoglobin, κFLC, prolactin, α1-microglobulin, and λFLC RRs. The FDY treatments obtained similar albumin RR in blood and slightly higher dialysate albumin loss, although the values were clinically acceptable. CONCLUSIONS: The most recently developed PEPA dialyzers in the HD modality were as effective as all treatments in the HDF modality and were clearly superior to high-flux helixone HD treatment. These results confirm that this dialyzer should be categorized within the medium cut-off (MCO) membrane classification.

Hemodiafiltration for children with stage 5 chronic kidney disease: technical aspects and outcomes.

Despite significant medical and technical improvements in the field of dialysis, the morbidity and mortality among patients with chronic kidney disease (CKD) stage 5 on dialysis remains extremely high. Hemodiafiltration (HDF), a dialysis method that combines the two main principles of hemodialysis (HD) and hemofiltration-diffusion and convection-has had a positive impact on survival when delivered with a high convective dose. Improved outcomes with HDF have been attributed to the following factors: HDF removes middle molecular weight uremic toxins including inflammatory cytokines, increases hemodynamic stability, and reduces inflammation and oxidative stress compared to conventional HD. Two randomized trials in adults have shown improved survival with HDF compared to high-flux HD. A large prospective cohort study in children has shown that HDF attenuated the progression of cardiovascular disease, improved bone turnover and growth, reduced inflammation, and improved blood pressure control compared to conventional HD. Importantly, children on HDF reported fewer headaches, dizziness, and cramps; had increased physical activity; and improved school attendance compared to those on HD. In this educational review, we discuss the technical aspects of HDF and results from pediatric studies, comparing outcomes on HDF vs. conventional HD. Convective volume, the cornerstone of treatment with HDF and a key determinant of outcomes in adult randomized trials, is discussed in detail, including the practical aspects of achieving an optimal convective volume.

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.

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.