Exploration of Daptomycin Adsorption by Polymethylmethacrylate Hemofilter In Vitro.

Blood purification therapy with cytokine-adsorbing hemofilters has been used to treat sepsis-associated hypercytokinemia. Polymethylmethacrylate (PMMA) hemofilters are frequently used for this purpose; however, adsorption and removal of teicoplanin, a therapeutic agent, have been reported. Similar concerns have been shared regarding daptomycin because its structure resembles that of teicoplanin; nevertheless, there have been no reported effects associated with daptomycin in this context. We studied the adsorption of daptomycin onto a PMMA hemofilter in vitro and investigated its adsorption onto hollow fiber membranes by adding cut PMMA membranes to a daptomycin solution. Additionally, the daptomycin solution was circulated in a dialysis circuit connected to a PMMA hemofilter, and changes in daptomycin content were examined. The daptomycin content decreased immediately after adding the hollow fiber membranes, similar to that observed for teicoplanin. The daptomycin content was lower than that of the standard reagent in the dialysis circuit model, reaching values below the measurement limit after 20 min. These results suggested that daptomycin was adsorbed and removed by the PMMA hemofilter. Encountering this effect during clinical use is plausible; therefore, daptomycin administration via a PMMA hemofilter should be avoided during blood purification therapy.

Cost Analysis of End-Stage Renal Disease in Pediatric Patients in Greece.

BACKGROUND/OBJECTIVES: The cost resulting from peritoneal dialysis (PD), conventional hemodialysis (HD) and online hemodiafiltration (OL-HDF) in pediatric patients with end-stage renal disease (ESRD) has not been estimated to date in Greece. The present single-center retrospective study aimed to estimate the mean annual cost of the above methods, as well as the individual components of this cost. METHODS: Twenty pediatric patients undergoing the three different methods of renal replacement therapy were included in this study. Their mean total annual cost was estimated by the method of micro-costing and the bottom-up approach. RESULTS: The mean total annual cost for PD patients (n = 7) was estimated at EUR 56,676.04; for conventional HD patients (n = 9), it was EUR 39,786.86; and for OL-HDF patients (n = 4), it was EUR 43,894.73. The PD method was found to be more expensive than the other two methods (p < 0.001 vs. conventional HD and p = 0.024 vs. OL-HDF). PD consumables used for daily application had the greatest contribution to the total annual cost. The total mean annual cost in the groups of patients undergoing HD and OL-HDF did not differ significantly (p = 0.175). The total operating cost of the renal dialysis unit had the greatest contribution to the total mean annual costs of both the conventional HD and OL-HDF techniques. CONCLUSIONS: This cost analysis provides useful information to healthcare policymakers who make decisions about the treatment of children with ESRD.

Hemodiafiltration May Be Associated with Senescence-Related Phenotypic Alterations of Lymphocytes, Which May Predict Mortality in Patients Undergoing Dialysis.

Senescence-resembling alterations on the lymphocytes of patients undergoing dialysis have been widely described. However, the pathophysiology behind these phenomena has not been clarified. In this study, we examined the impact of dialysis prescription on T and B lymphocytes, in patients undergoing dialysis.: T and B cell subsets were determined with flow cytometry in 36 patients undergoing hemodialysis and 26 patients undergoing hemodiafiltration, according to the expression of CD45RA, CCR7, CD31, CD28, CD57, and PD1 for T cells, and IgD and CD27 for B cells. The immune phenotype was associated with dialysis modality, hemofiltration volume, and mortality. Compared with hemodialysis, patients undergoing hemodiafiltration had a significantly decreased percentage of CD4+CD28-CD57- T cells [3.8 (2.4-5.3) vs. 2.1 (1.3-3.3)%, respectively, p = 0.002] and exhausted CD4+ T cells [14.1 (8.9-19.4) vs. 8.5 (6.8-11.7)%, respectively, p = 0.005]. Additionally, the hemofiltration volume was negatively correlated with CD8+ EMRA T cells (r = -0.46, p = 0.03). Finally, the increased exhausted CD4+ T cell percentage was associated with increased all-cause mortality in patients undergoing dialysis, independent of age. Hemodiafiltration, especially with high hemofiltration volume, may have beneficial effects on senescence-related immune phenotypes. Immune phenotypes may also be a predicting factor for mortality in patients undergoing dialysis.

Impact of convective clearance on intra-dialytic potassium removal in chronic dialysis patients.

INTRODUCTION: Hyperkalemia is frequently encountered and associated with cardio-vascular mortality in chronic hemodialysis (HD) patients. While online hemodiafiltration (OL-HDF) is thought to offer clinical benefit over high-flux HD, the impact of convective clearance on intra-dialytic potassium removal is unknown. METHODS: Chronic dialysis patients undergoing outpatient HD or OL-HDF at a single center attached to a university hospital were recruited in a prospective observational study. Spent dialysate along with clinical and biological variables were collected during a single mid-week session. RESULTS: We included 141 patients, with 21 treated with HD and 120 with OL-HDF. Mean age was 65.7 ± 15.6 years with 87 (61.7%) men. Mean intra-dialytic potassium removal was 69.9 ± 34.2 mmol. Patients on OL-HDF and HD have similar intra-dialytic potassium removal, with mean values of 69.1 ± 34.2 and 74.3 ± 35.0, respectively. In multivariate analysis, factors associated with intra-dialytic potassium removal were (decreasing order of effect size): dialysate potassium (ß -15.5, p < 0.001), pre-HD serum potassium (ß 9.1, p < 0.001), and session time (ß 7.8, p = 0.003). In OL-HDF patients, substitution flow was not associated with potassium removal. CONCLUSION: In chronic dialysis patients, convective therapy provided by OL-HDF does not affect potassium removal when compared with high-flux HD. Moreover, the importance of convective volume is not associated with potassium clearance in OL-HDF. Overall, session length and serum-to-dialysate potassium gradient are the main determinants of potassium clearance regardless of dialysis modality. Those results should inform clinicians on the optimal therapy in chronic dialysis patients in the era of OL-HDF.

Effect of hemodiafiltration and hemodialysis on mortality of patients with end-stage kidney disease: a meta-analysis.

INTRODUCTION: Previous randomized controlled trials (RCTs) and meta-analyses comparing Hemodiafiltration (HDF) with conventional hemodialysis (HD) on the effectiveness of HDF for mortality in end-stage renal disease (ESRD) patients have yielded contrasting results. Importantly, we sought to compile the available information to provide the most up-to-date and reliable evidence. METHODS: We systematically searched PubMed, Embase and Cochrane Library for RCTs up to January 14, 2024. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence. RESULTS: Our study involved 10 randomized controlled trials with 4654 chronic dialysis patients. Compared to hemodialysis, hemodiafiltration demonstrated a reduction in all-cause mortality (relative risk [RR] 0.84, 95% confidence intervals [CI] 0.72-0.99, P = 0.04) and cardiovascular mortality (RR 0.74, 95% CI 0.61-0.90, P = 0.002). However, it did not reduce the rate of sudden death (RR 0.92, 95% CI 0.64-1.34, P = 0.68) and infection-related mortality (RR 0.70, 95% CI 0.47-1.03, P = 0.07). A subgroup analysis revealed that HDF demonstrated superiority over high-flux hemodialysis in terms of all-cause mortality, while not over low-flux hemodialysis (RR 0.81, 95% CI 0.69-0.96, P = 0.01; RR 0.93, 95% CI 0.77-1.12, P = 0.44, respectively). Furthermore, a subgroup analysis for convection volume found that hemodiafiltration with a convection volume of 22 L or more reduced all-cause and cardiovascular mortality (RR 0.76, 95% CI 0.65-0.88, P = 0.0002, RR 0.73, 95% CI 0.54-0.94, P = 0.01, respectively). CONCLUSION: In maintenance hemodialysis patients, hemodiafiltration can reduce mortality compared to conventional hemodialysis. Furthermore, this effect is more pronounced in HDF with high convection volume.

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.

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.

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.

Depurative capacity toward medium molecules of the dialyzer Toray NV-U® Hydrolink™: A new hydrophilic membrane to perform online hemodiafiltration.

INTRODUCTION: New dialysis membranes with new properties are being developed to improve efficacy and tolerance. The hemocompatibility of a polymeric biomaterial is influenced by the layer of water at the blood membrane interface. The new dialyzer TORAY NV-U® has a membrane Hydrolink™, designed to suppress platelet adhesion and to improve the hemocompatibility. Until now, there is no experience in online hemodiafiltration (OL-HDF).The objective of the present study is to evaluate the efficacy of this new membrane in OL-HDF therapy compared to another membrane commonly used. Other objectives are to evaluate the inflammatory response, hemodynamic tolerance, and the anticoagulation regimes. METHODS: This is a prospective pilot study performed in five anuric patients receiving OL-HDF. For 1 month patients were kept with their usual dialyzer FX1000® (FMC). Subsequently, the dialyzer was changed to TORAY NV-U® (Hydrolink®) for 1 month. In the last dialysis session of each dialyzer, blood tests were performed to evaluate inflammation and depurative capacity. RESULTS: We did not find differences in medium size removal molecules and convective volume: FX1000®: 31 ± 9 l per session and Hydrolink™ 30 ± 8 l; p = 0.7); ß2microglobulin reduction ratio (RR) FX1000® FMC 83 ± 3%; Hydrolink™ 79 ± 4; p = 0.14; Myoglobin RR FX1000® FMC 72 ± 7%; Hydrolink™ 76 ± 4; p = 0.28. We did not find differences in inflammation parameters: serum IL6 with FX1000® 6.0 ± 4.2 pg/mL; Hydrolink™ 7.6 ± 5.0 pg/mL; p = 0.3.During all sessions with the two dialyzers there was adequate plasmatic filling, reaching 85 % filling. All patients had "good" dialyzer status in all dialysis sessions with TORAY NV-U®, while the dialyzer status with FX1000® was "good" in 20% of the sessions, "medium" in 30%, and "dirty" in the remaining 50% dialysis sessions. CONCLUSIONS: The new dialyzer Hydrolink™, TORAY NV-U® is not inferior to perform OL-HDF compared to dialyzers usually used for this therapy, and could allow decrease heparin doses. Further studies with a bigger sample size and longer follow-up will answer if Hydrolink improves inflammation and assess a better hemodynamic tolerance.

Echocardiographic Indices in Patients with End-Stage Renal Disease and Their Association with Hemodialysis-to-Hemodiafiltration Transfer: A Prospective Observational Study.

Background and Objectives: The assessment of cardiac function in patients with end-stage renal disease (ESRD) is vital due to their high cardiovascular risk. However, contemporary echocardiographic indices and their association with hemodialysis-to-hemodiafiltration transfer are underreported in this population. Materials and Methods: This prospective cohort study enrolled 36 ESRD patients undergoing hemodialysis-to-hemodiafiltration transfer, with baseline and 3-month post-transfer comprehensive echocardiographic assessments. The key parameters included the global work index, global constructed work, global wasted work (GWW), global work efficiency (GWE), and global longitudinal strain (GLS), with secondary measures from conventional echocardiography. The baseline measures were compared to general population reference values and changes pre- to post-transfer were analyzed using the Mann-Whitney U test. Results: Patients exhibited significant deviations from reference ranges in GWW (179.0 vs. 53.0-122.2 mmHg%), GWE (90.0 vs. 53.0-122.2%), and GLS (-16.0 vs. -24.0-(-16.0)%). Post-transfer left ventricular myocardial work and longitudinal strain remained unchanged (p > 0.05), except for increased GWW (179.0, IQR 148.0-217.0 to 233.5, IQR 159.0-315.0 mmHg%, p = 0.037) and improved mid-inferior peak systolic longitudinal strain ((-17.0, IQR -19.0-(-11.0) to -18.7, IQR -20.0-(-18.0)%, p = 0.016). The enrolled patients also showed higher left atrial diameters, left ventricular volumes, and mass, with impaired systolic function in both ventricles compared to reference values. Conclusions: This study highlights baseline impairments in contemporary echocardiographic measures (GWW, GWE, GLS) in ESRD patients versus reference values, but found no association between hemodialysis-to-hemodiafiltration transfer and most myocardial work and strain parameters.

Transitions and Long-Term Clinical Outcomes in Patients Admitted in Intensive Care Units Receiving Continuous Renal Replacement Therapy.

Introduction: Acute kidney injury (AKI) significantly disrupts vital renal functions and is a common and serious condition in intensive care units (ICUs). AKI leads to extended hospital stays, increases mortality rates, and often necessitates nephrology consultations. Continuous renal replacement therapy (CRRT) plays a central role in managing AKI, requiring a multidisciplinary approach involving nephrologists, intensivists, and anesthesiologists. This study examines the clinical profile and progression of AKI in ICU patients requiring CRRT, with a focus on CRRT indications and modalities. Materials and Methods: We conducted a single-center retrospective observational study on ICU patients with AKI requiring CRRT from January to December 2019. AKI diagnosis followed the RIFLE criteria, and patients who received CRRT for less than 36 h were excluded. Data collected included demographics, hemodynamic parameters, and renal function parameters, with follow-ups at 1 week, 1 month, 6 months, and 12 months. Statistical analyses evaluated outcomes and transitions between CRRT and other renal replacement therapies. Results: Among 123 evaluated patients, 95 met inclusion criteria. Fifteen patients received CRRT for less than 36 h, with an early mortality rate of 80%. The final cohort comprised 80 patients who underwent CRRT for over 36 h, with a mean age of 65.3 years (SD = 13.6) and a Charlson index of 6.4. Patients were categorized based on primary diagnosis into heart failure, cardiac surgery, sepsis, other surgeries, and miscellanea groups. Mortality rates were highest in the heart failure and miscellanea groups. Significant variability was observed in therapy transitions and long-term outcomes. Continuous venovenous hemodiafiltration (CVVHDF) was the most frequently used CRRT modality. Conclusions: This study highlights the variability in CRRT practices and the poor prognosis for critically ill patients with AKI requiring CRRT. Timely nephrology consultation and tailored treatment plans may improve patient outcomes and optimize CRRT utilization. Future research should focus on refining CRRT protocols and exploring preventive strategies for AKI.

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.

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.

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.

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.

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.

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).

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.

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.