Large Uremic Toxins Research Articles

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.

Unveiling the Clinical Benefits of High-Volume Hemodiafiltration: Optimizing the Removal of Medium-Weight Uremic Toxins and Beyond.

Dialysis treatment has improved the survival of patients with kidney failure. However, the hospitalization and mortality rates remain alarmingly high, primarily due to incomplete uremic toxin elimination. High-volume hemodiafiltration (HDF) has emerged as a promising approach that significantly improves patient outcomes by effectively eliminating medium and large uremic toxins, which explains its increasing adoption, particularly in Europe and Japan. Interest in this therapy has grown following the findings of the recently published CONVINCE study, as well as the need to understand the mechanisms behind the benefits. This comprehensive review aims to enhance the scientific understanding by explaining the underlying physiological mechanisms that contribute to the positive effects of HDF in terms of short-term benefits, like hemodynamic tolerance and cardiovascular disease. Additionally, it explores the rationale behind the medium-term clinical benefits, including phosphorus removal, the modulation of inflammation and oxidative stress, anemia management, immune response modulation, nutritional effects, the mitigation of bone disorders, neuropathy relief, and amyloidosis reduction. This review also analyzes the impact of HDF on patient-reported outcomes and mortality. Considering the importance of applying personalized uremic toxin removal strategies tailored to the unique needs of each patient, high-volume HDF appears to be the most effective treatment to date for patients with renal failure. This justifies the need to prioritize its application in clinical practice, initially focusing on the groups with the greatest potential benefits and subsequently extending its use to a larger number of patients.

#6760 EFFICACY OF HEMOSORPTION IN REMOVAL OF HIGH MOLECULAR WEIGHT UREMIC TOXINS IN CHRONIC HEMODIALYSIS PATIENTS

Abstract Background and Aims Symptoms associated with the accumulation of large uremic toxins (the development of chronic inflammation, accelerated progression of cardiovascular diseases and an increase in the incidence of protein-energy malnutrition) are common for patients who get chronic hemodialysis (HD) for a long time. HD effectively removes small and medium molecules (up to 15 kDa), while convection techniques, which are not always available, are used to remove substances of higher molecular weight. An alternative strategy for removing uremic toxins, especially large medium molecules, is the use of sorption techniques. The aim of the study was to compare the removal efficiency of substances with a molecular weight from 11.8 to 45 kDa using HD on a high-flux membrane and a combination of a high-flux membrane with hemosorption. Method The study included patients with a duration of hemodialysis therapy for more than 5 years. Blood sampling was carried out before and after the procedures, in the average RRT session per week. The following indicators were determined: β-2-microglobulin, leptin, free light chains (FLC) κ and λ, Il-6. The first HD session was performed on a Fresenius Fx-80 high-flux membrane. The second procedure (one week after) was carried out using the same filter, but with the connection of a Jafron HA130 sorption column (HD+HP). The duration of the both procedures was 4 hours. Blood flow did not exceed 300 ml/min. Results Total 10 patients were included in the study. Mean duration of renal replacement therapy was 12±5 years. The ratio of men and women was equal. Mean age 54±12 years. All patients used AV fistulas as vascular access. When determining and comparing the concentrations of β-2-microglobulin, leptin, Il-6, a comparable significant decrease in concentrations was noted after both procedures without significant statistical differences between the methods. At the same time, the efficiency of FLC removal on HD and HD+GP was convincingly different: - average kappa-FLC concentration change after HD was +1.8±9.1 mcg/ml, after HD+GP: -9.4±7.5 mcg/ml, p = 0.04. - average lambda -FLC concentration change after HD/HD+GP was +3.2±16.3 and -12.9±4.4 mcg/ml, respectively. p = 0.02. Conclusion The use of sorption techniques as an adjunct to standard HD therapy can increase the excretion of medium-large molecular substances, such as FLC kappa/lambda, which may help reduce the severity of symptoms associated with the accumulation of these uremic toxins. Additional studies are required to evaluate the clinical effectiveness of the new sorption method in chronic HD.

MO799IS COMBINATION OF MAINTENANCE HEMODIALYSIS WITH HEMOPERFUSION AN EFFECTIVE METHOD IN MANAGEMENT OF RENAL OSTEODYSTROPHY AND INFLAMMATION IN HEMODIALYSIS PATIENTS?

Abstract Background and Aims Some of the conditions which occur in maintenance hemodialysis (MHD) patients with a high incidence resulting in a decline in their quality of life, include malnutrition, renal osteodystrophy, refractory hypertension and chronic systemic inflammation. In developing countries, due to the low level of economic development, low-flux dialysis is the main means of extracorporeal blood purification therapy. But it can hardly remove the middle and large molecule uremic toxins and protein-bound toxins; as a result, the patients suffer from long-term complications and poor quality of life. In this study, we attempted to investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve their uremic complications. Method A total of 54 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into two groups: Group 1 (27 patients) received combined treatment of HD with hemoperfusion (HP) in this regimen: HD 2 times a week with HD+HP once a week two times in a row, then after two weeks, and afterwards once a month as a maintenance treatment. Group 2 (27 patients) was only undergoing maintenance HD 3 times a week. The clinical and laboratory properties of both groups were followed up for 18 months, whereas the primary outcomes included normal clinical data, high sensitive C-reactive protein (hsCRP), immunoreactive parathyroid hormone (iPTH), phosphorus (P04), calcium (Ca), albumin, iron (Fe), total iron binding capacity (TIBC), hemoglobin, Epo doses and types of hypertensive drugs. Results At the end of the 18-month observation, the serum concentration of albumin, P04, hsCRP, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower with Group 1 than with Group 2 (p<0.05). Whereas, higher levels of iPTH were noticed in group 1, but when the laboratory and clinical data are analysed of the group 1 alone a statistically significant lower values after the observational period are noticed especially in the serum values of iPTH (p<0.05), P04 (p<0.001), CRP (p<0.011), SBP and DBP (p<0.05). Conclusion HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body which is mostly shown through reducing the values of iPTH and hsCRP. These findings suggest a potential role for HD+HP in the treatment of inflammation and renal osteodystrophy as well, because lowering these values of iPTH leads to a normalization of other minerals which is expected and therefore leads to a stabilization of this long-term uremic complications, which can improve the overall general condition of the MHD patient.

MO880EFFECTIVENESS OF MEDIUM CUT-OFF VS HIGH FLUX DIALYZERS: A PROPENSITY SCORE MATCHING COHORT STUDY

Abstract Background and Aims According to emerging evidence, medium cut-off membrane improves clearance of molecules larger than 25 kDa, including larger uremic toxins. There is growing evidence on clinical effectiveness outcomes associated with the use of these membranes. Our aim was to evaluate clinical effectiveness of medium cut-off (HDx) versus high flux (HF-HD) dialyzers in terms of hospitalization rate and duration, cardiovascular event rate and survival in a HD prevalent cohort in Colombia through an observational, multicenter retrospective cohort analysis. Method Adult Prevalent HD patients (> 90 days in HD) at Baxter Renal Care Services Colombia were included between September 1st, 2017 to November 30th, 2017 (follow-up until 2 years). Socio-demographic and clinical characteristics of all patients were summarized descriptively. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline socio-demographic and clinical characteristics. Weighted incidence rate ratios (IRRs) and rates and duration of hospitalization and cardiovascular events according to dialyzer type were obtained using binomial negative regression with the weighting sample. Results We evaluated 1098 patients (37.7% women): 534 in HF-HD vs 564 in HDx (Table 1), median age was 60.6 years. Mean time on HD was 5.6 years (SD 5.51) for HF-HD and 5.88 for HDX (SD 5.48) We observed lower hospitalization rates in HDx group, (IRR HDx/HF-HD: 0.82 95% CI 0.69 to 0.98; p=0.03); and cardiovascular events rate, (IRR HDx/HF-HD: 0.65 95% CI 0.47 to 0.91; p=0.01) see Table 2. Main cause of hospitalization was cardio-cerebrovascular (Table 3). We observed no differences in hospitalization duration or survival. Conclusion We evaluated 1098 patients (37.7% women): 534 in HF-HD vs 564 in HDx (Table 1), median age was 60.6 years. Mean time on HD was 5.6 years (SD 5.51) for HF-HD and 5.88 for HDX (SD 5.48) We observed lower hospitalization rates in HDx group, (IRR HDx/HF-HD: 0.82 95% CI 0.69 to 0.98; p=0.03); and cardiovascular events rate, (IRR HDx/HF-HD: 0.65 95% CI 0.47 to 0.91; p=0.01) see Table 2. Main cause of hospitalization was cardio-cerebrovascular (Table 3). We observed no differences in hospitalization duration or survival.

Comparison of Circulating Levels of Uremic Toxins in Hemodialysis Patients Treated with Medium Cut-Off Membranes and High-Flux Membranes: Theranova in Sisli Hamidiye Etfal (THE SHE) Randomized Control Study

Introduction: Removal of uremic toxins is a main objective of hemodialysis; however, whether high-flux and medium cut-off (MCO) membranes differ as regards removal of middle and large uremic toxins is not clear. Objective: To compare medium cut-off and high-flux dialyzers as regards their intra- and interdialysis effect on circulating levels of middle and large uremic toxins and serum albumin. Methods: Fifty-two patients were randomized to have hemodialysis with either 3 months of high-flux dialyzer followed by 3 months of MCO or vice versa. Blood samples were taken before and after dialysis at the first and last sessions of each dialyzer for analyses of middle and large uremic toxins including inflammatory mediators and vascular endothelial growth factor (VEGF), and serum albumin. Results: Reduction rates were higher, and postdialysis levels of β-2 microglobulin, free kappa and lambda light chains, and myoglobulin were lower at the first and last sessions with MCO dialyzers compared to high-flux dialyzers (p < 0.05 for all). Last session predialysis levels of β-2 microglobulin, free kappa light chain, and free lambda light chain were lower than first session predialysis levels in MCO dialyzers as compared to high-flux dialyzers (p < 0.05 for all). Last session levels of interleukin-6, interleukin-10, interleukin-17, and interferon-gamma did not differ between dialyzers (p > 0.05 for all). VEGF level was lower in the MCO group compared to the high-flux group (p = 0.043). Last session level of serum albumin with MCO dialyzers was lower than that with high-flux dialyzers (3.62 [3.45–3.88] vs. 3.78 [3.58–4.02] g/L) (p = 0.04) and 6.7% lower (p < 0.001) than at the first session of MCO dialyzers. Conclusion: The decline in circulating levels of several middle and large uremic toxins including VEGF following hemodialysis was more pronounced when using MCO membranes as compared to high-flux membranes while their effect on inflammatory molecules was similar.

P1072COMPARISON OF UREMIC TOXINS, INFLAMMATORY MARKERS AND VEGF LEVEL WITH MEDIUM CUT-OFF MEMBRANES AND HIGH-FLUX MEMBRANES IN HEMODIALYSIS: THERANOVA IN SISLI HAMIDIYE ETFAL (THE SHE) STUDY

Abstract Background and Aims Mortality in hemodialysis have not changed since last 30 years which may be caused by inflammation and accumulation of middle and large uremic toxins. Medium cut-off (MCO) membranes are able to perform hemodialysis as effective as hemodiafiltration. Their effect on inflammatory molecules and vascular endothelial growth factor-C (VEGF), an independent factor effective on mortality, are not well known. The aim of the study was to compare intra and inter dialyzer performances of MCO and high-flux dialyzers regarding middle and large uremic toxin, inflammatory marker, VEGF and serum albumin level. Method This is a randomized, prospective, open-label, cross-over study (ClinicalTrials.gov: NCT03836508) approved by local ethic committee. Patients had hemodialysis with either 36 sessions of high-flux dialyzer followed by 36 sessions of medium cut-off dialyzer or vice versa. Pre and postdialysis levels for urea, creatinine, albumin, total protein, free kappa light chain, free lambda light chain, beta-2 microglobulin, myoglobulin levels were determined at first and last sessions of every dialyzer. Postdialysis level of middle and large uremic molecules have been determined by a formula to prevent hemoconcentration effect. Reduction rate for uremic toxins were calculated. Serum level of human VEGF, fibroblast growth factor-23 (FGF-23), interferon gamma (IFN-g), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-17A (IL-17A) levels were determined at first and last session of the each dialyzer. Results Fifty-two patients were enrolled to the study. Median age of patients was 56.40 (43.87-67.39) years. Median dialysis vintage was 4.77 (3.08-10.09) years. Reduction rates and postdialysis levels of free kappa and lambda light chain, myoglobulin, beta-2 microglobulin were lower both at first and last sessions in medium cut-off dialyzers compared to high-flux dialyzers (p&amp;lt;0.05 for all) (Table 1). Last session predialysis free kappa, free lambda, beta-2 microglobulin level was lower than first session predialysis levels in medium cut-off dialyzers (p&amp;lt;0.05 for all) (Table 2). Last session IL-6, IL-10, IL-17, IFN-gamma levels did not differ between dialyzers (p&amp;gt;0.05 for all). Vascular endothelial growth factor levels were 500.91 (363.80-679.15) pg/ml in medium cut-off group and 610.60 (450.63-1021.93) pg/ml in high-flux group (p=0,043). Predialysis serum albumin level at first session for MCO and high-flux groups were 3.88 (3.71-4.04) g/L and 3.75 (3.59-3.95) g/L, respectively (p=0.086) (Figure 1). After 3 months of hemodialysis, it was 3.62 (3.45-3.88) g/L in MCO group and 3.78 (3.58-4.02) g/L in high-flux group (p=0.04). Serum albumin level has decreased from 3.88 (3.71-4.04) g/L to 3.62 (3.45-3.88) g/L in 3 months during hemodialysis with MCO dialyzers (p=0.0001). It did not change significantly in high-flux group in the same time period (p=0.861). Conclusion MCO membranes not only decrease post dialysis levels of free kappa, free lambda, beta-2 microglobulin, myoglobulin but also decrease the third month predialysis levels of free kappa, free lambda, beta-2 microglobulin. They do not let the increase in myoglobulin level as seen in high-flux dialyzers. Even though the IL-6, IL-10, IL-17, IFN-gamma, FGF-23 levels did not differ, VEGF levels were lower in MCO dialyzer. The most important side effect of hemodialysis with MCO membranes is decreased serum albumin level.

P1112COMPARISON OF EFFICACY BETWEEN MAINTENANCE HEMODIALYSIS AND THEIR COMBINATION WITH HEMOPERFUSION IN PATIENTS UNDERGOING CHRONIC HEMODIALYSIS TREATMENT

Abstract Background and Aims The occurance of mid- and longterm uremic complications is related to the low clearance rate of middle and large molecule uremic toxins when hemodialysis (HD) alone is adopted. As the uremic toxins and their corresponding biological effects become increasingly clear, blood purification treatment that aims to remove these toxins, has developed from a stage of life-sustaining to improving the quality of life. The objective of this study was to evaluated demographic, clinical and laboratory data in patients who underwent the combination of maintenance hemodialysis with hemoperfusion (HP) and in those who recieved HD alone and to investigate whether this combination could improve the clearance rate of middle and large molecule uremic toxins. Method A total of 26 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into three groups: Group 1 (7 patients) received combined treatment of HD with HP biweekly (HD 2 times a week with HD+HP once a week), whereas Group 2 (10 patients) was given HD with high flux dialyzer and Group 3 (9 patients) was given HD with low flux dialyzer 3 times a week. This study was followed for 4 months. Before and after the observational period demographic and clinical data were taken from the medical history and blood samples were taken for hemoglobin (Hb), iron (Fe), total iron binding capacity (TIBC), albumin (Alb), calcium (Ca), phosphorus (P04) and parathyroid hormone (PTH). Results This study included 13 female and 13 male patients with a mean age of 41, 62 + 11.12 and a mean dialysis duration of 62, 78+53, 33 months. When it comes to baseline characteristics, patients of the group 3 were significantly older than patients in other groups (p=0.001). At the end of the four months observation period, the same difference according to age was noticed (p=0.01). Also, HD+HP group had significantly higher values of TIBC (p=0.006) and significantly lower serum levels of P04 (p=0.001). EPO doses were very similar in group 1 and 2, but in group 3 there were noticeably lower than in those two groups but without a significant difference. The serum levels of albumin were higher in group 3 compared to the other two groups but also without statistical difference. No statistical difference between groups after the follow up period was observed in terms of Hb, Fe, PTH, Ca, BMI, duration of dialysis treatment and vascular access. When groups are viewed individually, in the HD+HP group serum P04 levels were significantly lower after the 4 months off the follow up period than it was at the beginning (p=0.031) and also TIBC was significantly higher (p=0.018). In group 2 the values of TIBC were significantly lower after the follow up period than it was at the beginning (p=0.025). No significant difference was noticed in group 3 but serum PTH levels tends to decrease after 4 months compared to baseline measurement. Conclusion This combination treatment of HD with HP was superior to HD in reducing levels of phosphorus. These findings suggests a potential role of reducing the risk of cardiovascular events in this population especially when it is known that hyperphosphatemia has been pointed out as the primary culprit in the process of cardiovascular calcification. Also, patients who underwent the combined treatment showed higher values of TIBC but unfortunately no difference was noticed between Hb levels and EPO doses. These results eventually demonstrates their role in the improvement of renal disease anemia, which opens up the possibility of further research on a larger sample and over a longer period of time.

P1063PERFORMANCE OF MEDIUM CUT-OFF DIALYZERS IN EXPANDED HEMODIALYSIS PATIENTS IN COLOMBIA

Abstract Background and Aims Uremic toxins which are retained in ESRD include small solutes to large middle molecules. Large middle molecules play significant roles in immune modulation and cardiovascular morbidity and mortality. Expanded hemodialysis (HDx) enabled by innovative medium cut-off (MCO) membrane more effectively removes large uremic toxins vs current dialytic therapies. Aims: To evaluate the efficacy of MCO dialyzer in large middle molecules removal and pre-dialysis albumin levels after 24 weeks of treatment. Method This was an exploratory, prospective observational, multicenter cohort study. Prevalent patients on HD therapy for at least 90 days at the Renal Care Services (RCS) were included between June 6, 2018, to June 14, 2018. Uremic toxins removal was evaluated by measuring the reduction ratio (RR) of free light chains (FLC) κ, λ, Interleukin (IL) 6, IL-10, β2 Microglobulin (β2 M) and fibroblastic factor 23 (FGF-23) at 12 weeks ( w) of treatment, as well as the change in predialysis midweek serum level of β2M, FGF-23, factor XIV activity, and VII at baseline, 12 w and 24 w of treatment. A mixed-model repeated measures analysis (MMRM) was performed to identify statistical differences over time Results The RR of κ-FLC, λ-FLC, β2 M, and FGF-23 at week 12 showed a reduction between 46-72%; while in IL-6 RR was not significantly changed (Table 2). Predialysis serum levels decreased for β2m, FLCs and IL-6 and FGF 23 (Table 3). The decrease in albumin was within 5% from baseline. Twenty-two adverse events (AEs) occurred during the follow-up period; No AEs during HDx were deemed related to MCO membrane use. Conclusion MCO dialyzers are safe and effective in removing large MMs and decrease in the uremic toxins levels.

Large uremic toxins: an unsolved problem in end-stage kidney disease.

Patients with end-stage kidney disease (ESKD) on maintenance hemodialysis are subject to a high burden of inflammation and cardiovascular disease, driven at least in part by retention of uremic solutes. Existing dialysis technologies using high-flux membranes offer limited clearance of solutes >15 kDa. New approaches to improve the removal of large uremic toxins include the novel medium cut-off dialysis membranes with pores larger than those in high-flux membranes. These new membranes provide the potential to improve the clearance of large middle molecules up to 50 kDa. In this review, we discuss 18 uremic toxins with molecular weights between 15 and 60 kDa that are retained in ESKD, for which there is evidence of a link to inflammation and/or cardiovascular disease. These include inflammatory proteins, cytokines, adipokines and other signaling proteins. Improved clearance of this group of difficult to remove molecules has the potential to lead to improved outcomes in dialysis patients by reducing the burden of cardiovascular disease, which now needs to be assessed in robust clinical trials.

Assessment of the association between increasing membrane pore size and endotoxin permeability using a novel experimental dialysis simulation set-up

BackgroundMembranes with increasing pore size are introduced to enhance removal of large uremic toxins with regular hemodialysis. These membranes might theoretically have higher permeability for bacterial degradation products. In this paper, permeability for bacterial degradation products of membranes of comparable composition with different pore size was investigated with a new in vitro set-up that represents clinical flow and pressure conditions.MethodsDialysis was simulated with an AK200 machine using a low-flux, high-flux, medium cut-off (MCO) or high cut-off (HCO) device (n = 6/type). A polyvinylpyrrolidone-solution (PVP) was recirculated at blood side. At dialysate side, a challenge solution containing a filtrated lysate of two water-borne bacteria (Pseudomonas aeruginosa and Pelomononas saccharophila) was infused in the dialysate flow (endotoxin ≥ 4EU/ml). Blood and dialysate flow were set at 400 and 500 ml/min for 60 min. PVP was sampled before (PVPpre) and after (PVPpost) the experiment and dialysate after 5 and 55 min. Limulus Amebocyte Lysate (LAL) test was performed. Additionally, samples were incubated with a THP-1 cell line (24 h) and IL-1β levels were measured evaluating biological activity.ResultsThe LAL-assay confirmed presence of 9.5 ± 7.4 EU/ml at dialysate side. For none of the devices the LAL activity in PVPpre vs. PVPpost was significantly different. Although more blood side PVP solutions had a detectable amount of endotoxin using a highly sensitive LAL assay in the more open vs traditional membranes, the permeability for endotoxins of the 4 tested dialysis membranes was not significantly different but the number of repeats is small. None of the PVP solutions induced IL-1β in the THP-1 assay.ConclusionsA realisitic in vitro dialysis was developed to assess membrane translocation of bacterial products. LAL activity on the blood side after endotoxin exposure did not change for all membranes. Also, none of the PVPpost solutions induced IL-1β in the THP-1 bio-assay.

Comparison of the effects of different blood purification methods on removal of macromolecules in uremia

Objective To compare the effects of different blood purification methods on the removal of large and medium molecular toxins in patients with maintenance hemodialysis(MHD), and to provide the clinical basis for selecting suitable dialysis modalities to prevent or delay the long term complications of uremic patients. Methods 60 MHD patients with long term and stable hemodialysis were enrolled in this study. All of them were selected from the patients with insufficient hemodialysis.According to the digital table, 60 patients were randomly divided into high flux hemodialysis (HFHD)group and hemodiafiltration (HDF) group, 30 cases in each group. And before, 3 months and 6 months after dialysis, the serum β2-MG, PTH and Cys C after dialysis were tested. Results The clearance of PTH in the HFHD group[(286.34±127.33)pg/mL] was significantly higher than that in the HDF group[(376.04±141.74)pg/mL], the difference was statistically significant(t=2.45, P<0.05). The clearance of β2 -MG in the HDF group[(11.34±1.96)mg/L]was significantly higher than that in the HFHD group[(15.41±3.02)mg/L], the difference was significant(t=5.88, P<0.05). The clearance of Cys C in the HFHD group[(263.67±98.72)μg/dL]was significantly higher than that in the HDF group[(345.63±105.00)μg/dL], the difference was statistically significant(t=2.96, P<0.05). Conclusion Both two dialysis methods are very effective in the removal of large and medium molecular uremic toxins in patients. In the removal of patients with increased PTH, HFHD is more effective. In the removal of patients with increased β2-MG, HDF is more effective. In the removal of Cys C, HFHD is better. Key words: Hemodiafiltration; Uremia

What Is the Optimal Target Convective Volume in On-Line Hemodiafiltration Therapy?

Conventional diffusion-based dialysis modalities including high-flux hemodialysis are limited in their capacity to effectively remove large uremic toxins and to improve outcomes for end-stage chronic kidney disease (ESKD) patients. By increasing convective solute transport, hemodiafiltration (HDF) enhances solute removal capacity over a broad range of middle- and large-size uremic toxins implicated in the pathophysiology of chronic kidney disease. Furthermore, by offering flexible convection volume, on-line HDF permits customizing the treatment dose to the patient's needs. In addition, convective-based modalities have been shown to improve hemodynamic stability and to reduce patients' inflammation profile - both of which are implicated in CKD morbidity and mortality. Growing clinical evidence indicates that HDF-based modalities provide ESKD patients with a number of clinical and biological benefits, including improved outcomes. Interestingly, it has recently emerged that the clinical benefits associated with HDF are positively associated with the total ultrafiltered volume per session (and per week), namely convective dose. In this chapter, we revisit the concept of convective dose and discuss the threshold value above which an improvement in ESKD patient outcome can be expected. This particular point will be addressed by stratifying the level of efficacy of convective volumes, schematically defined as minimal, optimal, personalized, and maximal. In addition, factors and best clinical practices implicated in the achievement of an optimal convective dose are reviewed. To conclude, we show how HDF differs from standard hemodialysis and why HDF offers a paradigm shift in renal replacement therapy.

MCO Membranes: Enhanced Selectivity in High-Flux Class.

Novel MCO high-flux membranes for hemodialysis have been developed with optimized permeability, allowing for filtration close to that of the natural kidney. A comprehensive in vitro characterization of the membrane properties by dextran filtration is presented. The sieving profile of pristine membranes, as well as that of membranes exposed to blood for 40 minutes, are described. The effective pore size (Stokes-Einstein radius) was estimated from filtration experiments before and after blood exposure, and results were compared to hydrodynamic radii of middle and large uremic toxins and essential proteins. The results indicate that the tailored pore sizes of the MCO membranes promote removal of large toxins while ensuring the retention of albumin.

Optimal convection volume for improving patient outcomes in an international incident dialysis cohort treated with online hemodiafiltration

Online hemodiafiltration (OL-HDF), the most efficient renal replacement therapy, enables enhanced removal of small and large uremic toxins by combining diffusive and convective solute transport. Randomized controlled trials on prevalent chronic kidney disease (CKD) patients showed improved patient survival with high-volume OL-HDF, underlining the effect of convection volume (CV). This retrospective international study was conducted in a large cohort of incident CKD patients to determine the CV threshold and range associated with survival advantage. Data were extracted from a cohort of adult CKD patients treated by post-dilution OL-HDF over a 101-month period. In total, 2293 patients with a minimum of 2 years of follow-up were analyzed using advanced statistical tools, including cubic spline analyses for determination of the CV range over which a survival increase was observed. The relative survival rate of OL-HDF patients, adjusted for age, gender, comorbidities, vascular access, albumin, C-reactive protein, and dialysis dose, was found to increase at about 55 l/week of CV and to stay increased up to about 75 l/week. Similar analysis of pre-dialysis β2-microglobin (marker of middle-molecule uremic toxins) concentrations found a nearly linear decrease in marker concentration as CV increased from 40 to 75 l/week. Analysis of log C-reactive protein levels showed a decrease over the same CV range. Thus, a convection dose target based on convection volume should be considered and needs to be confirmed by prospective trials as a new determinant of dialysis adequacy.

Elimination of Large Uremic Toxins by a Dialyzer Specifically Designed for High-Volume Convective Therapies

Background: Unlike conventional hemodialysis treatments, which rely almost solely on diffusion-related mechanisms for solute removal, hemodiafiltration (HDF) allows more efficient removal of higher molecular weight toxins due to convective transport mechanisms. To facilitate the removal of these toxins in HDF treatment modalities, dialyzers with highly efficient high-flux membranes are necessary. This study assessed the large uremic toxin removal ability of a high-flux dialyzer (FX CorDiax 60) specifically designed to facilitate convective therapies compared with a standard high-flux dialyzer (FX 60). Methods: In an open, randomized, cross-over, single-center, controlled, prospective clinical study, 30 adult chronic hemodialysis patients were treated by post-dilution online HDF with the FX 60 or the FX CorDiax 60 dialyzer. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of blood urea nitrogen, phosphate, β₂-microglobulin (β₂-m), myoglobin, prolactin, α₁-microglobulin, α₁-acid glycoprotein, albumin and total protein as well as the elimination into dialysate was intraindividually compared for the two dialyzer types. Results: For FX CorDiax 60 versus FX 60, the RR was significantly higher for blood urea nitrogen (86.23 ± 4.14 vs. 84.89 ± 4.59%, p = 0.015), β₂-m (84.67 ± 3.79 vs. 81.30 ± 4.82%, p < 0.0001), myoglobin (75.23 ± 10.48 vs. 58.60 ± 12.1%, p < 0.0001), prolactin (72.96 ± 9.68 vs. 56.91 ± 13.01%, p < 0.0001) and α₁-microglobulin (20.89 ± 18.27 vs. 13.60 ± 12.50%, p = 0.016). There were no significant differences in the RR for phosphate, α₁-acid glycoprotein, albumin and total protein. Mass removal was significantly higher with the FX CorDiax 60 than with the FX 60 for β₂-m (0.26 ± 0.09 vs. 0.24 ± 0.09 g, p = 0.0006), myoglobin (1.83 ± 0.89 vs. 1.51 ± 0.76 mg, p = 0.0017), prolactin (0.17 ± 0.13 vs. 0.14 ± 0.08 mg, p = 0.02) and albumin (4.25 ± 3.49 vs. 3.01 ± 2.37 g, p = 0.03). Conclusions: This study demonstrates that treating patients with an FX CorDiax 60 instead of an FX 60 dialyzer in post-dilution HDF mode significantly increases the elimination of middle molecules.

Home haemodialysis and uraemic toxin removal: does a happy marriage exist?

Home-based methods of haemodialysis are becoming of increasing interest. In this article, we review theoretical and evidence-based aspects of dialysis adequacy in the home setting compared with those of standard in-centre dialysis. Owing to the flexibility it enables, home haemodialysis may allow reduced blood flow rates and the successful use of less-efficient access systems. With home haemodialysis, Kt/V(urea) targets should be pursued as recommended in current guidelines, taking into account that this parameter does not reflect a number of essential elements that affect adequacy, such as dialyser pore size or alternative timeframes-factors that might be applicable to modern home haemodialysis. The use of high-flux, large-pore haemodialysers is associated with improved removal of large uremic toxins and should be considered as standard in home haemodialysis where possible, although dialysis water purity is crucial. Large molecule removal is further enhanced by applying convective strategies (such as haemo[dia]filtration), but these strategies greatly increase technical complexity. Alternate-day haemodialysis is more desirable than the usual thrice-weekly approach to avoid complications at the end of the long weekend interval, and it is easier to implement such a regime at home than in-centre. Frequent, prolonged, and combined frequent and prolonged dialysis regimes are all associated with improved removal and improved outcomes. All three alternative timeframes are easier to apply at home than in-centre. Home haemodialysis offers increased flexibility in adopting dialysis regimes that make it possible to improve solute removal and, therefore, outcomes.

A Modified in vivo Flow Variation Technique of Microdialysis for Sampling Uremic Toxins in the Subcutaneous Interstitial Compartment

Background: Uremic toxins are typically measured in plasma and little is known of their interstitial concentrations. We undertook experiments to validate a microdialysis technique for simultaneous recovery of small and large uremic toxins in the subcutaneous interstitial fluid (ISF). Methods: Microdialysis catheters were inserted into the subcutaneous interstitium of 8 subjects (controls and uremic patients) and perfused using two different solutions at incremental flow rates to determine analyte recovery and ISF concentrations of urea and protein. Results: 10% dextran-40 perfusate allowed the determination of interstitial concentrations of urea and protein reliably, by virtue of the exponential decay of their concentrations in the microdialysate with incremental flow rates (R² = 0.63–0.99). Interstitial and plasma urea correlated well (r = 0.95), as did interstitial urea from distant anatomical sites (r = 0.96). Conclusion: Cutaneous microdialysis with dextran-40 allows measurement of small and large molecule concentrations in ISF, creating an opportunity to characterize ISF in uremia.