Switching from acetate to citrate dialysate in a central concentrate delivery system for high-volume online hemodiafiltration: a retrospective cohort study.

Interest in citrate-based dialysate (Cit-D) is growing due to its benefits, including anticoagulation and dialysis efficacy. However, research on safety and efficiency of Cit-D in high-volume hemodiafiltration (HDF) via central concentrate delivery system (CCDS) is scarce. This study aimed to investigate the safety and efficacy of Cit-D when switching from acetate-based dialysate (Acet-D) in high-volume HDF via CCDS. This is a retrospective analysis of 28 patients who underwent post-dilution online HDF via CCDS, who switched from Acet-D to Cit-D. The study period was divided into 3 periods for analysis: 12 weeks using Acet-D (AD period), the first 12 weeks using Cit-D (CD-1 period), and the second 12 weeks using Cit-D (CD-2 period). We collected the laboratory, dialysis, and safety parameters in each period from electrical medical records. After switching from Acet-D to Cit-D, heparin dosage decreased by 17%, whereas the incidence of complications did not increase. Kt/VBUN and urea reduction ratio increased by 4.6% and 2.1%, respectively. Pre-dialysis beta2-microglobulin concentration decreased after using Cit-D. The corrected calcium levels decreased in the CD-1 period compared to the AD period, but in CD-2, they subsequently increased to levels similar to those observed during the AD period. Symptomatic hypocalcemia did not occur, and there was no significant difference in the incidence of hyperparathyroidism. Endotoxin levels and the bacterial culture of ultrapure dialysate were unremarkable throughout all periods. These results might suggest that Cit-D could potentially offer advantages over Acet-D, such as reducing the heparin dose and increasing dialysis efficiency, in patients undergoing high-volume HDF using CCDS.

Online Hemodiafiltration: A New Perspective for Patients With End-Stage Renal Disease.

Introduction Online hemodiafiltration (OL-HDF) is the most effective renal replacement therapy (RRT), which allows the enhanced removal of small and large uremic toxins by combining diffusion and convective transport of solutes. Although the goal of OL-HDF is to provide greater clearance of solutes with a preference for intermediate molecules responsible for many of the complications of chronic kidney disease (CKD), the studies reported to date and their meta-analyses are conflicting in nature and do not show a significant advantage of convective therapies on patient prognosis. Materials and methods At the Clinic of Nephrology and Dialysis, University Hospital "St. Marina", Varna, Bulgaria, 41 patients were monitored in a retrospective study for a two-year period, randomized into two groups, conducting OL-HDF after dilution and hemodialysis (HD) with the aim of studying the effect of convective therapies on the clinical outcome, the achieved quality of life, and the prognosis of the patient. Results The study found a significantly higher quality of life in patients undergoing OL-HDF with significantly higher values ​​of indicators of dialysis adequacy and nutritional status, better control of the anemic syndrome with the reduction of erythropoietin doses, significantly lower frequency of episodes of intradialytic hypotension with improved recovery, and 3.6-fold lower risk of death compared with conventional dialysis. Discussion Three major randomized controlled trials have compared survival outcomes in patients receiving HD or post-dilution OL-HDF, reporting conflicting results. Meta-analyses of the published studies have also been unable to provide a clear and definitive answer regarding the potential benefits of choosing one treatment over the other. Overall mortality, anemia, phosphate control, and small molecule clearance appear to be insufficiently influenced by the treatment method. On the other hand, cardiovascular mortality, hemodynamic stability, and clearance of middle and protein-bound molecules seem to be better in patients treated with OL-HDF. Conclusions Despite the conflicting data reported so far, OL-HDF is associated with better clinical outcome and prognosis for end-stage renal disease (ESRD) patient and undoubtedly warrants extensive future study with a view to improved quality of life in the growing dialysis population.

Effective Extracorporeal Treatment of Metformin-Associated Lactic Acidosis using Continuous Venovenous Hemodiafiltration.

Background: The prevalence of type 2 diabetes mellitus has surged globally. Metformin is recommended as the first-line oral treatment. However, metformin-associated lactic acidosis (MALA) is recognized as a rare but potentially dangerous complication. The pathogenesis of MALA is multifactorial, primarily resulting from the interference of metformin with mitochondrial function and hepatic gluconeogenesis, leading to lactate accumulation. Risk of MALA escalates with impaired kidney function, poorly controlled diabetes, fasting, and liver dysfunction. Case Description: A 57-year-old woman with diabetes and hypertension presented with prolonged gastrointestinal symptoms. During this episode she continued using metformin. She had severe metabolic acidosis and acute kidney injury. Continuous venovenous hemodiafiltration was initiated, resulting in significant clinical improvement and normalized arterial blood gas parameters within 16 hours. Discussion: The pharmacokinetic properties of metformin facilitate efficient elimination via hemodialysis and/or hemofiltration. Continuous venovenous hemodiafiltration emerges as effective for MALA treatment. In the case described the calculated metformin clearance during continuous venovenous hemodiafiltration was notably higher than reported values, possibly due to residual renal clearance. Clinical improvement occurred despite elevated metformin levels, suggesting a lack of correlation between metformin levels and patient outcomes. Comorbidities rather than metformin levels guide treatment decisions in MALA. Conclusion: This case underscores the efficacy of continuous venovenous hemodiafiltration in the treatment of MALA, suggesting its potential as a standard therapeutic approach. However, further research is needed to elucidate the complex interplay between metformin levels, clinical presentation, (extracorporeal) treatment modalities and outcome in MALA. LEARNING POINTS: Continuous venovenous hemodiafiltration seems to be an efficient and effective treatment to eliminate metformin in patients with metformin-associated lactic acidosis.The metformin level does not seem to correlate with the clinical condition of the patient.For a comparison between the effectiveness of different renal replacement therapies in metformin-associated lactic acidosis, more research is needed.

Further improvement of circuit survival in citrate based continuous renal replacement therapy.

Background: Continuous renal replacement therapy (CRRT) is the most frequently used modality of renal replacement therapy (RRT) in critical care patients with acute kidney injury (AKI). Adequate CRRT delivery can be challenging, due to problems with circuit patency. To improve circuit patency, we developed a new CRRT protocol using continuous veno-venous hemodiafiltration (CVVHDF) with 3.0 mmol/l regional citrate anticoagulation (CVVHDF/RCA3.0) as our first choice RRT modality. Methods: Retrospective comparison of efficacy and safety of a CVVHDF/RCA3.0 protocol with our former continuous veno-venous hemofiltration protocol with 2.2 regional citrate anticoagulation (CVVH/RCA2.2) in adult critically ill patients with AKI requiring CRRT between 25 April 2020 and 24 October 2021. Results: In total, 56 patients (257 circuits) and 66 patients (290 circuits) were included in the CVVH/RCA2.2 and CVVHDF/RCA3.0 groups, respectively. Median circuit survival was significantly higher in patients treated with CVVHDF/RCA3.0 (39.6 (IQR 19.5-67.3) hours) compared to patients treated with CVVH/RCA2.2 (22.9 (IQR 11.3-48.6) hours) (P < .001). Higher body weight and higher convective flow were associated with a lower circuit survival. Metabolic control was similar, except for metabolic alkalosis that occurred less frequently during CVVHDF/RCA3.0 (19% of patients) compared to CVVH/RCA2.2 (46% of patients) (P = .006). Conclusions: CRRT circuit survival was longer with CVVHDF/RCA3.0 compared to CVVH/RCA2.2. CRRT circuit survival was negatively associated with higher body weight and higher convective flow.

The CONVINCE randomized trial found positive effects on quality of life for patients with chronic kidney disease treated with hemodiafiltration.

In the CONVINCE trial, the primary analysis demonstrated a survival benefit for patients receiving high-dose hemodiafiltration (HDF) as compared with high-flux hemodialysis (HD). A secondary objective was to evaluate effects on health-related quality of life (HRQoL); assessed in eight domains (physical function, cognitive function, fatigue, sleep disturbance, anxiety, depression, pain interference, social participation) applying instruments from the Patient-Reported Outcome Measurement Information System (PROMIS) before randomization and every three months thereafter. In total 1360 adults with dialysis-dependent chronic kidney disease, eligible to receive high-flux HDF (23 liters or more), were randomized (1:1); 84% response rate to all questionnaires. Both groups reported a continuous deterioration in all HRQoL domains. Overall, raw score changes from baseline were more favorable in the HDF group, resulting in a significant omnibus test after a median observation period of 30 months. Most relevant single raw score differences were reported for cognitive function. Patients receiving HDF reported a decline of -0.95 units (95% confidence interval - 2.23 to +0.34) whereas HD treated patients declined by -3.90 units (-5.28 to - 2.52). A joint model, adjusted for mortality differences, utilizing all quarterly assessments, identified a significantly slower HRQoL decline in physical function, cognitive function, pain interference, and social participation for the HDF group. Their physical health summary score declined -0.46 units/year slower compared to the HD group. Thus, the CONVINCE trial showed a beneficial effect of high-dose hemodiafiltration for survival as well as a moderate positive effect on patients' quality of life, most pronounced with respect to their cognitive function. REGISTRATION: NTR7138 on the International Clinical Trials Registry Platform.

Citrate Dialysate with and without Magnesium Supplementation in Hemodiafiltration: A Comparative Study Versus Acetate.

The choice of dialysate buffer in hemodialysis is crucial, with acetate being widely used despite complications. Citrate has emerged as an alternative because of its favorable effects, yet concerns persist about its impact on calcium and magnesium levels. This study investigates the influence of citrate dialysates (CDs) with and without additional magnesium supplementation on CKD-MBD biomarkers and assesses their ability to chelate divalent metals compared to acetate dialysates (ADs). A prospective crossover study was conducted in a single center, involving patients on thrice-weekly online hemodiafiltration (HDF). The following four dialysates were compared: two acetate-based and two citrate-based. Calcium, magnesium, iPTH, iron, selenium, cadmium, copper, zinc, BUN, albumin, creatinine, bicarbonate, and pH were monitored before and after each dialysis session. Seventy-two HDF sessions were performed on eighteen patients. The CDs showed stability in iPTH levels and reduced post-dialysis total calcium, with no significant increase in adverse events. Magnesium supplementation with CDs prevented hypomagnesemia. However, no significant differences among dialysates were observed in the chelation of other divalent metals. CDs, particularly with higher magnesium concentrations, offer promising benefits, including prevention of hypomagnesemia and stabilization of CKD-MBD parameters, suggesting citrate as a viable alternative to acetate. Further studies are warranted to elucidate long-term outcomes and optimize dialysate formulations. Until then, given our results, we recommend that when a CD is used, it should be used with a 0.75 mmol/L Mg concentration rather than a 0.5 mmol/L one.

The Roller Coaster of Lamotrigine Levels: Successful Treatment of Massive Lamotrigine Overdose With Continuous Veno-Venous Hemodiafiltration and Rifampin.

Lamotrigine is a commonly used anticonvulsant in treating seizures and bipolar disorder, but there is very limited literature on the management of its toxicity. Case reports have been published suggesting the potential role of hemodialysis in lowering serum lamotrigine levels, as well as sodium bicarbonate and lipid emulsion in treating dysrhythmia. After previously reported therapies failed to stabilize the patient's condition, the case presents our successful treatment experience using continuous veno-venous hemodiafiltration (CVVHDF) to stabilize lamotrigine levels, as well as intravenous rifampin as adjunctive therapy to facilitate lamotrigine metabolism. This is a 66-year-old male who was found unresponsive after a lamotrigine overdose. His first lamotrigine level was 42.3 ug/mL. Hemodialysis was started on hospital day 1. Despite hemodialysis sessions, his lamotrigine level rebounded with worsening neurological and cardiac symptoms. On hospital day 3, he developed wide-QRS complex tachyarrhythmia and hemodynamic instability with a lamotrigine level of 66.9 ug/mL. Sodium bicarbonate was given without effect. Lipid emulsion was administered which terminated the arrhythmia. CVVHDF and rifampin were started and lamotrigine levels have continuously downtrended since. He was successfully extubated on day 7. Lamotrigine level became undetectable on day 9. The patient was discharged to a psychiatric facility without any neurological or mobility impairment on day 10. The continuous drug clearance provided by CVVHDF over intermittent hemodialysis may have provided additional benefit in lamotrigine level stabilization, while rifampin use in this case may have further accelerated lamotrigine metabolism. As the first case reporting CVVHDF and rifampin use, our experience suggests their potential roles in managing severe lamotrigine toxicity.

Comparison of hemodialysis urea clearance using spent dialysate and Kt/Vurea equations.

INTRODUCTION: Dialysis adequacy is traditionally calculated from pre- and post-hemodialysis session serum urea concentrations and expressed as the urea reduction ratio, or Kt/Vurea. However, with increasing hemodiafiltration usage, we wished to determine whether there were any differences between standard Kt/Vurea equations and directly measured spent dialysate urea clearance. METHODS: Urea clearance was measured from collected effluent dialysate and compared with various other methods of Kt/Vurea calculation, including change in total body urea from measuring pre- and post-total body water with bioimpedance and the Watson equation, by standard Kt/V equations, and online clearance measurements using effective ionic dialysance (OLC). RESULTS: We compared urea clearance in 41 patients, 56.1% male, mean age 69.3 ± 12.6 years with 87.8% treated by hemodiafiltration. Reduction in total body urea was greater when estimating changes in total body urea, compared to measured dialysate losses of 58.4% (48.5-67.6) vs 71.6% (62.1-78), p < 0.01. Sessional urea clearance (Kt/Vurea) was greater using the online Solute-Solver program compared to OLC, median 1.45(1.13-1.75) vs 1.2 (0.93-1.4), and 2nd generation Kt/V equations 1.3 (1.02-1.66), p < 0.01, but not different from estimated total body urea clearance 1.36 (1.15-1.73) and dialysate clearance 1.36 (1.07-1.76). The mean bias compared to the Solute-Solver program was greatest with OLC (-0.25), compared to second-generation equations (-0.02), estimated total body clearance (-0.02) and measured dialysate clearance (-0.01). CONCLUSION: This study demonstrated that the result from equations estimating urea clearance indirectly from pre- and postblood samples from hemo- and hemodiafiltration treatments was highly correlated with direct measurements of dialysate urea clearance.

Effect of online hemodiafiltration on quality of life, fatigue and recovery time: a systematic review and meta-analysis.

The present systematic review and meta-analysis aims to compare the effect of bicarbonate hemodialysis and HDF on quality of life (QoL), fatigue, and time to recovery in end-stage renal disease (ESRD) patients. Searches were run on January 2024 and updated on 3 March 2024 in the following databases: Ovid MEDLINE (1985 to present); Ovid EMBASE (1985 to present); Cochrane Library (Wiley); PubMed (1985 to present). Ten articles were fully assessed for eligibility and included in the investigation. Compared to HD, online HDF had a pooled MD of the mental component score (MCS) of the SF-36 of 0.98 (95% CI - 0.92, 2.87; P = 0.31). and of the physical component score (PCS) of 0.08 (95% CI - 1.32, 1.48; P = 0.91). No significant heterogeneity was observed (Chi2 = 4.85; I2 = 38%; P = 0.18 and Chi2 = 3.85; I2 = 22%; P = 0.28, respectively). Studies that compared the QoL assessed through the Kidney Disease Questionnaire or KDQOL-SF and show that HDF does not improve QoL when compared with HD, in most studies. In five out of seven studies, HDF was not significantly more effective than HD in improving fatigue. The length of the recovery time resulted in similar in patients receiving HDF and HD in all studies included in the present review. HDF is not more effective than HD in improving QoL and fatigue and in reducing the length of time of recovery after dialysis.

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.

Protein-Bound Uremic Toxins and Inflammation Process in Hemodialysis Patients: Is There a Role for Adsorption Hemodiafiltration?

INTRODUCTION: Despite major advances in the field of dialysis, there are still some unmet needs such as reducing inflammation through adequate depuration. It is well known that the wide spectrum of pro-inflammatory and pro-atherosclerotic uremic toxins are inefficiently removed by current dialysis techniques. Adsorption seems to be an extra tool to remove toxins, but its effect and optimization have not been widely studied. The aim of this report was to present preliminary results regarding the possibility of performing hemodiafiltration with a highly adsorptive polymethylmethacrylate membrane. METHODS: The study was first conducted in 10 patients in which the safety and feasibility of hemodiafiltration with PMMA BG-U 2.1 membrane were tested through measurement of hemolysis indices, transmembrane pressures, and dialysis adequacy. Twenty patients were prospectively observed for 18-month period in which they consecutively underwent standard hemodialysis, standard post-dilution hemodiafiltration, and polymethylmethacrylate-based post-dilution hemodiafiltration. Protein-bound uremic toxins concentrations and inflammatory markers were measured throughout the observed period. RESULTS: HDF-PMMA was inferior to HDF in convective volume, but KT/V was similar, and no differences were noted in operating pressures during the two treatments. During HDF-PMMA period of treatment, we observed a significant reduction of CPR levels, and HDF-PMMA was superior to all other treatments in hepcidin removal even if this did not significantly affect hemoglobin levels. HDF-PMMA could significantly reduce indoxyl sulfate (indoxyl) concentration over a period of 6 months but not for p-cresyl sulfate (p-cresyl). CONCLUSION: PMMA BG-U 2.1 membrane can be safely and efficiently used in hemodiafiltration. Moreover, as these preliminary results show, adding adsorption properties to convection and diffusion enabled an increased removal of indoxyl uremic toxin associated to a reduction in inflammation markers as CRP and hepcidin without any negative impact on albumin levels.

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).

Controversy on the CONVINCE study findings: the PRO take / Controvérsia sobre os achados do estudo CONVINCE: a perspectiva PRO

ABSTRACT 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.

RESUMO O estudo CONVINCE, publicado recentemente no New England Journal of Medicine, revela uma redução inovadora de 23% no risco relativo de mortalidade por todas as causas entre pacientes renais em estágio terminal submetidos à hemodiafiltração de alto volume de convecção. Esse achado significativo desafia o uso convencional da hemodiálise de alto fluxo e oferece esperança de melhoria dos desfechos em pacientes com doença renal crônica. Embora algumas controvérsias cerquem os achados do estudo, incluindo preocupações sobre a generalização e as causas de óbito, é essencial reconhecer o desenho do estudo e seus principais desfechos. O estudo CONVINCE, parte do projeto HORIZON 2020, inscreveu 1.360 pacientes e demonstrou a superioridade da hemodiafiltração na redução da mortalidade por todas as causas em geral, bem como em subgrupos específicos de pacientes (idosos, HD de curta duração, não diabéticos e aqueles sem problemas cardíacos). Curiosamente, demonstrou-se que a hemodiafiltração teve um efeito protetor contra infecções, incluindo a COVID-19. Pesquisas futuras abordarão sustentabilidade, efeitos de escalonamento da dose, identificação de subgrupos especialmente propensos a se beneficiar e a relação custo-benefício. No entanto, por ora, os achados apoiam fortemente uma adoção mais ampla da hemodiafiltração na terapia renal substitutiva, marcando um avanço significativo na área.

Hemodiafiltration: a synergy yet to be convincing / Hemodiafiltração: uma sinergia ainda não convincente

ABSTRACT 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.

RESUMO A tentativa desesperada de melhorar a mortalidade, morbidade, qualidade de vida e desfechos relatados pelos pacientes em indivíduos em hemodiálise levou a diversas tentativas de aprimorar os diferentes modos, frequências e durações das sessões de diálise nas últimas décadas. Nada foi mais atrativo do que a combinação de difusão e convecção na forma de hemodiafiltração. Apesar das evidências concretas de melhor depuração de moléculas de peso médio e melhor estabilidade hemodinâmica, evidências tangíveis para apoiar a adoção universal ainda estão distantes. Os benefícios de sobrevida observados em grupos selecionados que provavelmente toleram a hemodiafiltração com melhor acesso vascular e com menor carga de comorbidades precisam ser estendidos aos pacientes reais em diálise, que são mais velhos do que a população estudada e apresentam uma carga de comorbidades significativamente maior. As exigências técnicas do início da hemodiafiltração, os custos associados e os benefícios incrementais almejados, juntamente com os desfechos relatados pelos pacientes, precisam ser melhor explorados antes de se recomendar a hemodiafiltração como o modo de escolha.

High volume online hemodiafiltration: a global perspective and the Brazilian experience / Hemodiafiltração on-line de alto volume: uma perspectiva global e a experiência brasileira

ABSTRACT 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.

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.

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.

Hemodiafiltration versus Hemodialysis in End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Rationale & Objective: The use of hemodiafiltration (HDF) as a kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD) has sparked a debate regarding its advantages over conventional hemodialysis (HD). The present study aims to shed light on this controversy by comparing mortality rates and cause-specific deaths between ESKD patients receiving HDF and those undergoing HD. Study Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). The search was conducted using PubMed, EMBASE, and Cochrane Central on July 1, 2023. Setting & Participants: Adult patients with ESKD on regular KRT. Exposure: Studies with participants undergoing HDF. Outcomes: Primary outcomes were all-cause mortality, cardiovascular (CV) mortality, deaths related to infections, and kidney transplant. We also evaluated the endpoints for deaths related to malignancy, myocardial infarction, stroke, arrhythmias, and sudden death. Analytical Approach: We included RCTs evaluating HDF versus HD. Crossover trials and studies with overlapping populations were excluded. Two authors independently extracted the data following predefined search criteria and quality assessment. The risk of bias was assessed with Cochrane's RoB2 tool. Results: We included 5 RCTs with 4,143 patients, of which 2,078 (50.1%) underwent HDF, whereas 2,065 (49.8%) were receiving HD. Overall, HDF was associated with a lower risk of all-cause mortality (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.73-0.91; P < 0.001; I2 = 7%) and a lower risk of CV-related deaths (RR, 0.75; 95% CI, 0.61-0.92; P = 0.007; I2 = 0%). The incidence of infection-related deaths was also significantly different between therapies (RR, 0.69; 95% CI, 0.50-0.95; P = 0.02; I2 = 26%). Limitations: In individual studies, the HDF groups achieved varying levels of convection volume. Conclusions: Compared with those undergoing HD, patients receiving HDF experienced a reduction in all-cause mortality, CV mortality, and infection-related mortality. These results provide compelling evidence supporting the use of HDF as a beneficial intervention in ESKD patients undergoing KRT. Registration: Registered at PROSPERO: CRD42023438362.

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.

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.

Delayed post-dialysis recovery times are associated with relative changes in intracellular and extracellular fluid ratios between different body compartments.

INTRODUCTION: Hemodialysis patient groups have advocated reducing dialysis fatigue and symptoms. We investigated whether compartmental fluid shifts were associated with peri-dialytic fatigue and symptoms. METHODS: Sessional dialysis records of patients reporting both a short and delayed recovery (<1 h and ≥1 h) with corresponding bioimpedance measurements were reviewed. RESULTS: One hundred and twenty-four patients reported both short and delayed recovery times, mean age 66.0 ± 14.8 years, 66.1% male. Differences between sessions included higher distress thermometer [4 (1-6) vs. 3 (0-5)], fatigue [4 (0-9) vs. 2 (0-7)], total symptom scores [20.5 (12.3-34.5) vs. 16 (7-28)], change in extracellular water to total body water ratios between body compartments [right leg/left arm 2.36 (1.23-4.19) vs. 1.28 (0.12-2.01), all p < 0.01] with delayed recovery, and more hemodialysis than hemodiafiltration sessions (χ2 4.6, p = 0.02). CONCLUSION: Sessions with prolonged recovery times were associated with more peri-dialytic symptoms, psychological distress, and hemodialysis mode, and greater changes in compartmental fluid shifts.