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.

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.

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.

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.

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.

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.

Optical Real-Time Cardiorenal Toxin Uric Acid Measurement During Hemodialysis Using a Miniaturized Optical Sensor.

Patients with chronic kidney disease (CKD) are at higher cardiovascular risk than the general population. Cardiovascular diseases, vascular calcification among them, are the leading cause of death in these patients. Factors influencing vascular calcification are oxidative stress, inflammation, and accumulation of uremic toxins during CKD. Uric acid is a cardiorenal toxin that accumulates in the case of kidney malfunction. The primary therapy for replacing kidney function and removing toxins from end-stage renal disease patients is hemodialysis. Effective removal of toxins can be estimated by blood or dialysate lab analysis or optical monitoring. In this study, the authors tested a miniaturized optical sensor for monitoring uric acid levels and removal for the first time in a more extensive clinical study, including Hemodialysis (HD) and Post-dilutional online hemodiafiltration (HDF) procedures with different settings in Tallinn, Estonia. The results (Mean±SD, Lab vs. Sensor) of the uric acid concentration 57.20±34.05 vs. 57.22±33.09 µmol/L, reduction ratio 68.72±10.91 vs. 67.89±12.48 %, and total removed amount 7.00±2.10 vs. 7.33±2.29 mmol did not differ significantly from the values obtained from the clinical laboratory (p<0.05).Clinical Relevance-During this study, a miniaturized optical sensor was tested for the first time in the clinic in different dialysis settings. The results confirm that the sensor is reliable for regularly monitoring cardiorenal toxin uric acid removal during hemodialysis.

Are medium cut-off membranes the future, or the promising reality for chronic hemodialysis patients?

The development of hemodialysis (HD) membranes has substantially advanced in the last decade. This has resulted in the manufacturing of medium cut-off membranes (MCO) whose internal architecture is based on greater pore size and a smaller diameter, thus promoting the clearance of particles of greater size as well as retrofiltration. Multiple studies have proven their efficacy in the clearance of uremic mid-sized molecules such as ß2-microglobulin, free light chains, and some interleukins; this clearance is far superior with MCO membranes when compared with high-flux HD, and similar to that obtained with online hemodiafiltration. This review summarizes the results of the most relevant clinical studies of this membrane in terms of uremic toxin clearance, as well as the features of some clinical outcomes such as quality of life and hospitalizations.

The effect of hemodiafiltration vs. high-flux hemodialysis on alpha 1-microglobulin level and dialysate albumin loss using a dialyzer surface area of 2.6 m².

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 alpha 1-microglobulin (A1M). In this study, we tested a high-flux dialyzer, BIOPURE (Biorema) 260 HF, with a surface area (SA) of 2.6 m2, in terms of A1M removal and concurrent albumin loss in dialysate while receiving 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' hourly dialysate albumin and pre/post dialysis concentrations of A1M were measured. The dialyzer used in this study resulted in significantly higher A1M RR of 41.9±7.93% with HDF than with HF-HD 27.12±7.65% (p < 0.001), and a median cumulative dialysate albumin loss of 2.97g (IQR 1.98 - 3.37), and 0.67g (IQR 0.49 - 1.13) with HDF and HF-HD, respectively. In conclusion, the dialyzer BIOPURE (Biorema) 260 HF (SA 2.6 m2) is efficient in eliminating A1M, especially with OL-HDF compared to HF-HD, with acceptable albumin loss in the dialysate.

Effects of high-flux hemodialysis and hemodiafiltration on the mortality of patients with end-stage kidney disease: a meta-analysis.

BACKGROUND: High-flux hemodialysis (HFHD) is widely used in hemodialysis centers and is the mode of hemodialysis actively recommended by the guidelines. Additionally, hemodiafiltration (HDF) is widely used in clinical practice. However, there are some inconsistencies in the results of studies on the effects of HDF and HFHD, which has caused controversy regarding which of these two dialysis modalities to select. OBJECTIVE: To explore the effect of HFHD and HDF on the survival of patients with end-stage kidney disease (ESKD). METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and VIP databases was conducted, focusing on cohort studies and randomized controlled trials on hemodialysis in patients with ESKD using HFHD or HDF. A meta-analysis of all-cause mortality and cardiovascular mortality was conducted using Review Manager 5.3 software, and fixed and random effect models were applied according to the heterogeneity results. RESULTS: A total of 13 studies, including six cohort studies and seven randomized controlled trials, were included in the final analysis. The results revealed that HFHD had no statistically significant effect on the all-cause mortality (odds ratio (OR): 1.16, 95% confidence interval (CI): 0.86, 1.57) or cardiovascular mortality (OR: 0.86, 95% CI: 0.64, 1.15) of patients with ESKD. However, compared with HDF, HFHD reduced the infection mortality rate (OR: 0.50, 95% CI: 0.33, 0.77). CONCLUSIONS: Compared with HDF, HFHD has no obvious benefits for all-cause mortality or cardiovascular mortality in patients with ESKD, but reduced risk of infection-related death.

Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

BACKGROUND: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS: A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS: In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

A 15-Year Retrospective Study of Supportive Extracorporeal Therapies Including Plasma Exchange and Continuous Venovenous Hemodiafiltration of 114 Adults with Acute Liver Failure Awaiting Liver Transplantation.

BACKGROUND Recently, there has been a recommendation to utilize a combination of supportive extracorporeal therapies, specifically plasma exchange and continuous venovenous hemodiafiltration, in patients with acute liver failure. This 15-year retrospective study aimed to evaluate supportive extracorporeal therapy, including plasma exchange and continuous venovenous hemodiafiltration, for 114 adults with acute liver failure awaiting liver transplant. MATERIAL AND METHODS In this retrospective study, the medical records of 1288 adult patients who underwent liver transplantation and 161 adult patients who received alternative therapy were analyzed; 114 patients who received combined supportive extracorporeal therapy for acute liver failure were included in the study. Biochemical laboratory data were compared before and after therapy. RESULTS The study included 50 male and 64 female patients. The first group (34 patients) recovered with liver transplantation, and 4 patients died in the first year after liver transplantation. In the second group (80 patients), 66 patients recovered without liver transplantation, while 14 patients died within the first 2 weeks after therapy. All patients showed significant reductions in serum hepatic function tests (alanine transaminase, aspartate transaminase, and total bilirubin), ammonia, and prothrombin time/international normalized ratio after discontinuation of combined supportive extracorporeal therapy (P<0.01). There was also a significant improvement in the hemodynamic parameter. CONCLUSIONS This combined extracorporeal therapy can be used as a supportive treatment for both recovery and bridge to liver transplantation in patients with acute liver failure. In addition, treatment can be continued until liver regeneration and until a usable donor is found.

Extracorporeal Techniques Based on Adsorption: Nomenclature, Hardware, and Circuit Design.

Sorbents have been utilized in the past for intoxication and poisoning, but their spectrum of clinical application is now expanding. Hemoadsorption (HA) is still indicated for toxin and poison removal, but other molecules are considered appropriate targets for this blood purification modality. HA combined with hemodialysis (HA + HD) has been proposed for end-stage kidney disease patients to remove molecules that are not easily removed by classic HD or hemodiafiltration. More recently, a rationale for the use of sorbents in critical illness, sepsis, and acute kidney injury has emerged due to the proposed humoral theory behind these disorders. Pathogenetic circulating molecules in critical illness (damage- and pathogen-associated molecular patterns) cannot be sufficiently removed by classic continuous renal replacement therapies. New sorbent-based extracorporeal therapies have therefore been designed to remove these molecules, offering potential biological and clinical benefits. There is also the possibility of employing selective sorbents to target specific molecules or to perform nonspecific HA for a wide spectrum of molecules. Moreover, there is the possibility of separating plasma from blood and then applying adsorption to plasma or of combining HA with other extracorporeal therapies. Here, we describe a complete appraisal of current available techniques utilizing adsorption.

Combined Hemoperfusion-Hemodialysis in End-Stage Renal Disease Patients.

Despite advances in dialysis technology, a high level of morbidity and mortality is still present in end-stage renal disease patients undergoing maintenance dialysis. This has been in great part correlated with accumulation of uremic toxins that cannot be adequately removed by classic dialysis membranes and techniques. Improvements have been made in enhancing both membrane permeability and convection rates as in the case for expanded hemodialysis (HD) and hemodiafiltration, but these techniques still present limitations or cannot be performed due to technical reasons. Considering the abovementioned limitations of current dialysis techniques, the additional use of adsorption as a solute removal mechanism may represent an interesting option. Recent studies have underlined the significant improvement in the levels of medium-large retention solutes and toxin-related symptoms using a combination of hemoperfusion with HD at least in a session per week. These studies need further confirmation, but they may represent the doorway to further improve patient's outcome in maintenance dialysis.

A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients.

OBJECTIVES: To develop a population pharmacokinetic (PK) model with data from the largest polymyxin B-treated patient population studied to date to optimize its dosing in hospitalized patients. METHODS: Hospitalized patients receiving intravenous polymyxin B for ≥48 hours were enrolled. Blood samples were collected at steady state and drug concentrations were analysed by liquid chromotography tandem mass spectrometry (LC-MS/MS). Population PK analysis and Monte Carlo simulations were performed to determine the probability of target attainment (PTA). RESULTS: One hundred and forty-two patients received intravenous polymyxin B (1.33-6 mg/kg/day), providing 681 plasma samples. Twenty-four patients were on renal replacement therapy, including 13 on continuous veno-venous hemodiafiltration (CVVHDF). A 2-compartment model adequately described the PK with body weight as a covariate on the volume of distribution that affected Cmax, but it did not impact clearance or exposure. Creatinine clearance was a statistically significant covariate on clearance, although clinically relevant variations of dose-normalized drug exposure were not observed across a wide creatinine clearance range. The model described higher clearance in CVVHDF patients than in non-CVVHDF patients. Maintenance doses of ≥2.5 mg/kg/day or ≥150 mg/day had a PTA ≥90% (for non-pulmonary infections target) at a steady state for minimum inhibitory concentrations ≤2 mg/L. The PTA at a steady state for CVVHDF patients was lower. DISCUSSION: Fixed loading and maintenance doses of polymyxin B seemed to be more appropriate than weight-based dosing regimens in patients weighing 45-90 kg. Higher doses may be needed in patients on CVVHDF. Substantial variability in polymyxin B clearance and volume of distribution was found, suggesting that therapeutic drug monitoring may be indicated.

Daily practice evaluation of the paediatric set of a next-generation long-term haemodialysis machine.

BACKGROUND: From 2006 to 2020, 24% of children starting haemodialysis in France weighed < 20 kg. Most new-generation long-term haemodialysis machines do not propose paediatric lines anymore but Fresenius has validated two devices for use in children above 10 kg. Our aim was to compare the daily use of these two devices in children < 20 kg. METHODS: Retrospective single-center evaluation of daily practice with Fresenius 6008® machines, and low-volume paediatric sets (83 mL), as compared to 5008® machines with paediatric lines (108 mL). Each child was treated randomly with both generators. RESULTS: A total of 102 online haemodiafiltration sessions were performed over 4 weeks in five children (median body weight 12.0 [range 11.5-17.0] kg). Arterial aspiration and venous pressures were maintained respectively over - 200 mmHg and under 200 mmHg. For all children, blood flow and volume treated per session were lower with 6008® vs. 5008® (p < 0.001), median difference between the two devices being 21%. In the four children treated in post-dilution mode, substituted volume was lower with 6008® (p < 0.001, median difference: 21%). Effective dialysis time was not different between the two generators; however, the difference between total duration of session and dialysis effective time was slightly higher (p < 0.05) with 6008® for three patients, due to treatment interruptions. CONCLUSION: These results suggest that children between 11 and 17 kg should be treated with paediatric lines on 5008® if possible. They advocate for modification of the 6008 paediatric set to decrease resistance to blood flow. The possibility to use 6008® with paediatric lines in children below 10 kg deserves further studies.

Toxicokinetics of metformin overdose treated with CVVHDF.

A 53-year-old man died following a reported ingestion of 80 g of his metformin tablets resulting in severe, refractory shock and metformin-associated lactic acidosis. His peak serum metformin concentration was 53 µg/mL (therapeutic range 1-2 µg/mL), peak lactic acid concentration was 49.7 mmol/L, and arterial pH nadir was 7.06. He died despite vasopressors and renal replacement therapy [RRT; both intermittent hemodialysis (IHD) and continuous venovenous hemodiafiltration (CVVHDF)]. Serial metformin concentrations during CVVHDF suggested a half-life of 33-h. Similar to previous reports of RRT for metformin toxicity, CVVHDF appears to provide first-order elimination of metformin.

An extended kinetic model-based correction factor equation to account hemodialysis post-treatment hemoconcentration.

The hemoconcentration effect for middle weight solutes in hemodialysis is corrected by oversimplified methods based on hematocrit changes or distribution volume variations. Here we implemented a variable volume dual pool kinetic model targeted at obtaining a precise correction factor equation for extracellularly distributed solutes based on relevant kinetic parameters such as the ultrafiltration to dry weight ratio UF/DW, the dialyzer clearance, Kd, the intercompartment mass-transfer coefficient, Kc, and the central compartment to extracellular volume ratio, α. More than 300,000 solutions of the model were computed, performing a sweep among physiological values of the proposed kinetic parameters, resulting in a linear regression denoted by the expression fcorr = 1.0707 - 5.2246 (UF/DW) - 0.0005 Kd - 0.0004 Kc - 0.0007 α, with an excellent coefficient of determination R2 = 0.983. The presented fcorr provides a substantial extension of the currently implemented methods to estimate the hemoconcentration factor for middle and high molecular weight extracellular distributed solutes in hemodialysis.