Middle Molecules Research Articles

Dual Layer Mixed Matrix Hollow Fiber Membranes for Outside-In Filtration of Human Blood Plasma

Hemodialysis mainly removes small water-soluble uremic toxins but cannot effectively remove middle molecules and protein-bound uremic toxins. Besides, the therapy is intermittent leading to fluctuating blood values and fluid status which adversely impacts patients’ health. Prolonged hemodialysis could improve the removal of toxins and the development of portable and wearable artificial kidneys could offer more flexibility in the dialysis scheme. This would enhance patients’ overall health, autonomy, mobility and flexibility, allowing patients to participate in social and economic life. However, during prolonged hemodialysis, blood clots could obstruct the fiber lumen, resulting in a decrease of the effective membrane surface area available for toxin removal. The outside-in filtration (OIF) mode, wherein blood flows through the inter-fiber space instead of through the fiber lumina, has been applied widely in blood oxygenators to prevent fiber clotting, but not in hemodialysis. In this study, we present for the first time the development of a mixed matrix membrane (MMM) for OIF of human blood plasma. This MMM combines diffusion and adsorption and consists of a polymeric membrane matrix with activated carbon (AC) particles on the inside layer, and a polymeric particle-free layer on the outer fiber layer. Our results show that in vitro MMM fibers for OIF demonstrate superior removal of the protein-bound uremic toxins, indoxyl sulfate and hippuric acid, compared to both earlier MMM fibers designed for inside-out filtration mode and commercial high-flux fibers.

Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 Dialyzer: A Randomized Controlled Trial.

Expanded hemodialysis therapy enabled by medium cut-off membranes may promote greater clearance of larger middle molecules that comprise putative uremic solutes than conventional high-flux dialysis. This randomized trial evaluated the efficacy and safety of hemodialysis treatment with a medium cut-off dialyzer. Clinically stable patients on maintenance hemodialysis were randomized to receive dialysis with either a medium cut-off dialyzer (Theranova 400) or a high-flux dialyzer (Elisio-17H) over 24 weeks of treatment. The primary safety end point was the predialysis serum albumin level after 24 weeks of treatment. The primary efficacy end point was the reduction ratio of free λ light chains at 24 weeks of treatment. Among 172 patients on maintenance hemodialysis, mean age was 59±13 years, 61% were men, 40% were Black, and mean dialysis vintage was 5±4 years. Of the 86 patients randomized to each dialyzer, 65 completed the trial in each group. The reduction ratio for the removal of free λ light chains was significantly higher in the Theranova 400 group compared with the Elisio-17H group after 4 weeks (39% versus 20%) and 24 weeks (33% versus 17%; both P<0.001). Among secondary end points, the Theranova 400 group demonstrated significantly larger reduction ratios at 4 and 24 weeks for complement factor D, free κ light chains, TNFα, and β2-microglobulin (P<0.001 for all), but not for IL-6. Predialysis serum albumin levels were similar between groups after 24 weeks (4 g/dl with the Theranova 400 and 4.1 g/dl with the Elisio-17H), consistent with noninferiority of the Theranova 400 dialyzer in maintaining predialysis serum albumin levels after 24 weeks of treatment. Hemodialysis therapy with the Theranova 400 dialyzer provides superior removal of larger middle molecules, as exemplified by free λ light chains, compared with a similar size high-flux dialyzer, while maintaining serum albumin level. A Multi-Center, Prospective, Randomized, Controlled, Open-Label, Parallel Study to Evaluate the Safety and Efficacy of the Theranova 400 Dialyzer in End Stage Renal Disease (ESRD) Patients, NCT03257410.

In vitro Cas9-assisted editing of modular polyketide synthase genes to produce desired natural product derivatives

One major bottleneck in natural product drug development is derivatization, which is pivotal for fine tuning lead compounds. A promising solution is modifying the biosynthetic machineries of middle molecules such as macrolides. Although intense studies have established various methodologies for protein engineering of type I modular polyketide synthase(s) (PKSs), the accurate targeting of desired regions in the PKS gene is still challenging due to the high sequence similarity between its modules. Here, we report an innovative technique that adapts in vitro Cas9 reaction and Gibson assembly to edit a target region of the type I modular PKS gene. Proof-of-concept experiments using rapamycin PKS as a template show that heterologous expression of edited biosynthetic gene clusters produced almost all the desired derivatives. Our results are consistent with the promiscuity of modular PKS and thus, our technique will provide a platform to generate rationally designed natural product derivatives for future drug development.

TO012HOW DIFFERENT IS THE CLEARANCE OF LARGE MIDDLE MOLECULES AND INFLAMMATORY MARKERS FROM EXPANDED HEMODIALYSIS THERAPY COMPARED TO ONLINE HEMODIAFILTRATION?

Abstract Background and Aims Expanded hemodialysis (HDx) with a medium cut-off dialyzer, Theranova® 500, can achieve a middle molecule clearance but its efficacy or comparison with HDF is still unknown. It is still unknown on how large middle molecules and inflammation markers are affected over time with a medium cut-off dialyzer. This study compared the purifying effectiveness of Theranova® 500 dialyzer with respect to online Hemodiafiltration (OL-HDF). Method Sixty-three patients who were already receiving HDF were evaluated and 43 were randomized by residual renal function. Twenty-one patients received treatment with HDx using Theranova® 500 and 22 patients remained in HDF in post-dilution mode, using a high-flux dialyzer, Polyflux® 170H, for up to 24 weeks. The dialysis time and the adequacy parameters for both arms were the same. Large middle molecules were measured (kappa immunoglobulin free light chains [κ-FLC], lambda immunoglobulin free light chains [λ-FLC], chitinase-3-like protein 1 [YKL-40], fibroblast growth factor 23 [FGF-23] and serum beta-2 microglobulin [β2M]), ; and inflammatory markers (high sensitivity C-reactive protein [hs-CRP], pentraxin - 3 [PTX-3], interleukin-6 [IL-6], interleukin-10 [IL-10]) at 12 weeks of treatment; and its change from baseline to weeks 12 and 24 in mid-week pre-dialysis. The method of measurement was the immunoassay. Siemens immunoassay was used for FLCs. Results HDx with Theranova® 500 demonstrated comparable results to OL-HDF with convective volume 24.4±3.2 L in terms of reduction rate (RR) of middle molecules (κ-FLC, λ-FLC, FGF-23 and β2M) at 12 weeks of treatment. HDx demonstrated similar performance to HDF in mid-week pre-dialysis plasma levels of middle molecules from baseline, at 12 and 24 weeks of treatment. Greater RR of YKL-40 at 12 weeks of treatment was seen in HDx group when compared to HDF (58.1% vs 42.4%; p≤0.0001), and there was a difference in the pre-dialysis β2M change from Baseline values between the groups (-0.60 for HDx arm and +3.28 for HDF arm, p=0.46). HDx with Theranova® 500 demonstrated comparable results to HDF in terms of reduction rate (RR) of inflammatory markers (hs-CRP, PTX-3, IL-6 and IL-10) at 12 weeks of treatment. There were no differences in the parameters of adequacy of dialysis between both arms. Both treatments were effective in maintaining pre-dialysis albumin and fibrinogen levels throughout the study. There were no significant adverse events related to the safety of Theranova. Conclusion HDx with Theranova® 500 is an emergent, effective and safe hemodialysis therapy that showed a purifying efficacy at least comparable to OL-HDF.

P1105CAN BETTER EFFICACY OF MIDDLE WEIGHT MOLECULES REMOVAL IN DIALYSIS PATIENTS TREATED WITH MEDIUM CUT-OFF MEMBRANES PREDICT SUPERIORITY OVER CONVENTIONAL HIGH FLUX DIALYSERS?

Abstract Background and Aims During last two decades there was a significant improvement in dialysis field, especially with introducement of high flux haemodialysis and on-line haemodiafiltration. In recent years, expanded haemodialysis has emerged as a new attempt to imrove effectiveness of dialysis. These so called medium cut-off membranes (MCO), allow removal of wider range of uremic toxins, especially middle weight molecules, most of which have important role in chronic inflammation and mortality. The aim of this prospective pilot study was to evaluate the effectiveness of middle molecules and other uremic toxins removal in patients treated with medium cut-off membrane (Theranova 500tm, Baxter), compared with patients on conventional high flux dialysis programme. Method We examined 10 patients on chronic haemodialysis programme, five of them dialyzed with Theranova 500tm dialyser for one year, and other five patients dialyzed with high flux membranes (polysulfone membrane, 1.8m2) during the same period. Patients were matched according to their age, sex, main disease, and the beginning of dialysis. Analyzed laboratory parameters were urea, creatinine, calcium, phosphorus, PTH, and hemoglobin, on the beginning of the study and after one year follow up, while hepcidin and β2 microglobulin levels were measured only in the end of follow up period. We used descriptive and analytic statistical methods (T test for independent and dependent means). Results Patients were divided in two groups, Group 1 - dialyzed with Theranova, and Group 2- patients on high flux haemodialysis, both followed during one year period (Group 1: 63.2±7.01 years, 3 males and 2 women, one of them with polycystic kidney disease (PCKD), the other four with hypertension as main disease, median dialysis time 54.6±8.32 months, Group 2: 63±6 years, 3 males, 2 women, main disease in one was PCKD, in other four hypertension, median dialysis time 53.6±17.98months). Our patients didn’t differ statistically in basic examined laboratory parameters on the beginning of examination (mean urea 21.38±2.15 vs. 27.44±3.93 mmol/ (p&amp;gt;0.05), mean creatinine 936±88.5 vs. 927.6±98.8µmol/L, mean albumin 40±2.54 vs 39.8±2.77g/L (p&amp;gt;0.05), mean calcium 2,24±0.16 vs 2.21±0.17mmol/L (p&amp;gt;0.05), mean phosphorus level 1,84±0.39 vs 1.67±0.56mmol/L (p&amp;gt;0.05), mean parathyroid hormone level 266.16±279.64 vs 236.14±43.99pg/mL (p&amp;gt;0.05), and mean hemoglobin 122.2±5.72 vs 106.4±8.62g/L (p&amp;gt;0.05). In patients on high flux haemodialysis programme there was no significant change in examined parameters during one year follow-up (for all examined parameters p value was &amp;gt;0.05). After switching the first group on Theranova dialysers for one year there was small but statistically significant rise in urea (23.26±2.02mmol/L, p&amp;lt;0.05), and also statistically significant decrease in serum creatinine level (840.2±75.34µmol/L, p&amp;lt;0.05) in this group, while other parameters were not statistically significant. Comparing two groups after one year follow up, there was statistically significant higher level of hemoglobin in the first group (112.2±7.46 vs. 102g/L ±4.47, p&amp;lt;0.05), and statistically significant decrease of beta-2 microglobuline (27.41±2.58 vs. 33.82± 2.47ng/mL, p&amp;lt;0.05) and hepcidin (75.64±32.2 vs 100.26±10.58ng/mL, p&amp;lt;0.05), while other parameters didn’t show statistical significance. Conclusion Our results implicate better clearance of middle weight molecules (B2M, hepcidin) in patients treated with Theranova 500 tm membrane, which could suggest anti-inflammatory effect of medium cut-off membranes, additionaly with the higher hemoglobin level after one year treatment, comparing to conventional high flux dialysis. Our results are promising, but need to be confirmed in larger randomized trials.

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.

P1392ANALYSIS OF CALCIFYING POTENTIAL OF UREMIC SERUM FROM HAEMODIALYSIS PATIENTS TREATED WITH A MEDIUM CUT-OFF (THERANOVA) DIALYSER: A PROSPECTIVE, CROSS-OVER STUDY

Abstract Background and Aims The retention of a large number of solutes that are normally excreted or metabolized by the kidney is responsible for the classical symptoms of haemodialysis (HD) patients. These molecules are defined as uremic toxins and can be classified into three groups: small water-soluble molecules, middle molecules and protein-bound toxins. Recently, efforts were put in order to develop dialysis membranes that allow the removal of large-middle molecules without clinically relevant albumin loss. These dialysers are the medium cut-off (MCO) membranes, which allow the removal of middle molecules up to approximately 50,000 Da. We performed a prospective, open-label, controlled, cross-over pilot study comparing expanded HD (HDx) with MCO membrane Theranova and conventional HD in 20 patients. Method Ten patients underwent conventional HD high-flux dialyser and 10 patients underwent HDx for 3 months, later the patients switched and received the other treatment for a further 3 months. We then analyzed the pro-calcifying effect of patient uremic serum in a model of high-phosphate (Pi) induced calcification in vascular smooth muscle cells (VSMCs). Results In this study each patient was the control of himself and, interestingly, we found a tendency of less pro-calcifying potential of serum from patients when treated with HDx, in comparison with HD (6.6±1.1, 5.6±0.6 and 6.7±1.0, OD/mg protein, baseline HD, 0-3 HDx and 3-6 HD, months, respectively; and 4.7±0.7 vs 3.2±0.2, OD/mg protein, 0-3 HD vs 3-6 HDx, months, respectively) (Figure). Investigating the major mechanisms involved in high-Pi induced calcium deposition, we found that serum from patients when treated with HDx induced less necrosis in VSMCs, compared with HD (3.2±0.8 vs. 0.9±0.1, necrosis enrichment factor, 0-3 HD vs. 3-6 HDx, months, respectively). Nevertheless, no differences were found between the different dialysis treatment in the serum potential to induce apoptosis and to modulate the expression of a panel of genes involved in VSMC osteoblastic-differentiation such as BMP2, RUNX2, osteocalcin, MGP, OPN, and elastin. In the effort to characterize the difference in uremic toxin profile during the two different dialysis treatments, we measured a panel of protein-bound uremic toxins which have been shown to promote vascular calcification and /or bone loss and shown a significant increased removal by HDx of 3-indoxyl sulfate (30.6±13.2 vs -17.1±10.2 Δ%; 0-3 HD vs 3-6 HDx, months; p&amp;lt;0.05; and -21.1±11.4 vs 54.4±33.2 Δ%; 0-3 HDx vs 3-6 HD, months; p&amp;lt;0.05), indole 3-acetic acid (43.1±16.9 vs -2.3±10.9 Δ%; 0-3 HD vs 3-6 HDx, months; p&amp;lt;0.05), CMPF (61.8±27.6 vs -16.1±9.6 Δ%; 0-3 HD vs 3-6 HDx, months; p&amp;lt;0.05), and kynurenine (44.2±12.9 vs -0.2±6.8 Δ%; 0-3 HD vs 3-6 HDx, months; p&amp;lt;0.05). Conclusion These preliminary data suggest a role for HDx in reducing the calcifying potential of uremic serum. Our findings are promising and they need to be confirmed in larger studies.

P1098THE CHANGE OF PLASMA SCLEROSTIN AND OTHER BIOMARKERS IN HEMODIALYTIC PATIENTS USING DIALYZER WITH MEDIUM CUT-OFF MEMBRANE

Abstract Background and Aims Protein-bound toxins and uremic toxins with middle molecular weight usually develop uremic symptoms in patients with advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). Although the effect on uremic toxicity of the molecules is not proven yet, middle molecules or larger middle molecules is regarded with important substance concerning of development of uremic symptoms and cardiovascular complication, particularly in CKD patients. Hemodialysis (HD) or hemodiafiltration (HDF) using dialyzer with high flux membrane provided improved clearance for uremic toxins with middle molecular weights. However, uremic toxins with larger middle molecular weight could not be easily removed through above methods. Medium cut-off (MCO) membrane can remove larger middle molecules which can be not removed through high flux membrane and HDF. From this perspective, chronic use of MCO membrane lowering the plasma concentration of larger middle molecules associated with cardiovascular complications including vascular calcification may give beneficial effect, particularly in patients with ESRD. Method Twenty-five patients undergoing chronic hemodialysis were prospectively analyzed for 6 months. We randomly divided enrolled patients into two groups: control group and MCO group. Patients in the control group used dialyzer with high flux membrane and patients in MCO group used dialyzer with MCO membrane. The enrolled patients performed hemodialysis thrice a week during 6 months. We measured plasma levels of several biomarkers at baseline and 3-month and 6-month through the multiplexing using Luminex® technology. In this prospective study, we performed comparative analysis with larger middle molecules, such as CXCL16, sclerostin, and FGF-23, in both groups. Results The plasma levels of all biomarkers at baseline did not show significant difference between two groups (CXCL16: p =0.904, Sclerostin: p =0.322, FGF-23: p =0.065, respectively). However, plasma sclerostin levels at 3-month and 6-month were significantly lower in MCO group (p = 0.060, p &amp;lt;0.005, respectively). In addition, even after analysis of covariance through ANCOVA analysis, plasma sclerostin levels at 3-month and 6-month were significantly lower in MCO group compared with the control group (p = 0.042, p =0.001, respectively). But, there was no a significant decrease of plasma sclerostin levels according to time, particularly in MCO group (p = 0.157, p =0.412, respectively) (Figure 1). Conclusion This study showed the 6-month outcome for changes of the plasma levels of larger middle molecules, including CXCL16, sclerostin, and FGF-23, particularly in dialytic patients using dialyzer with MCO membrane. Plasma sclerostin associated with vascular calcification showed decreasing tendency during 6 months after application of MCO membrane, but, there was no statistical significance. However, plasma levels of sclerostin were significantly lower in dialytic patients using MCO membrane than those using high flux membrane at 3 and 6 months, respectively. Therefore, hemodialysis using dialyzer with MCO membrane may be an option to attenuate cardiovascular complications in ESRD patients.

P1109HDX: IS IT A BETTER WAY TO DIALYSE?

Abstract Background and Aims Inadequate dialysis has been linked to reduced quality of life, increased symptom burden and increased risk of cardiovascular illness in patients with chronic kidney disease. This is especially significant in long-term haemodialysis patients who have little to no residual urine output and are thus almost entirely dependent on good quality dialysis to remove toxins and fluid. In most conventional haemodialysis modes middle molecule clearance is inadequate. This in turn plays an important part in causing multiple complications. HDx is a new type of haemodialysis being introduced using Theranova® dialyzer. This claims to have medium cut-off membranes, functioning similar to a kidney, hence providing better clearance of middle molecules, whilst selectively preventing loss of proteins from the body. In order to test the safety and efficacy of HDx using Theranova® we tried it in a cohort of our patients in the form of an audit. Our primary objective was to find out the effect of HDx on quality of life. Secondary objective was to determine whether HDx improves blood biochemistry, with a reduction in medication &amp; transfusion needs. Method Thirty seven Haemodialysis patients were switched from hemodiafiltration to HDx, out of these 3 patients were transplanted, 2 patients died, 1 patient switched back and 7 patients were transferred to satellite units. Audit was continued with the remaining 24 patients. All patients completed an Integrated Palliative Care Outcome Score (IPOS) prior to commencing on HDx and then at six months. Blood parameters including phosphorous, calcium, haemoglobin, Ferritin and CRP were measured monthly and mean values of 6 months before and after HDx initiation were compared. Comparison of erythropoietin, intravenous iron and packed red blood cell transfusion requirements pre and post HDx commencement were also undertaken. Results No obvious adverse effects were noted with use of HDx dialysis. All patients had an improvement in overall IPOS scores after being on HDx for 6 months. Shorter post dialysis symptom recovery times were also noted. 13 patients had a decrease in their erythropoietin requirements, in 2 patients requirement remained the same, 9 patients had increase in their requirement however 3 of these patients had been requiring packed red blood cell transfusion prior to HDx commencement, no longer required transfusion. We found an overall improvement in patients iron infusion need. 11 patients had a dose reduction, with 4 of these patients no longer requiring iron. 9 patients continued to have the same requirements. 4 patients had an increase in iron dose, but 3 of these patients previously being transfusion dependant no longer required regular transfusions. We also noted that with use of HDx clotting risk was reduced and patients who were switched from Evodial (heparin coated dialyzer membranes) to HDx did not have increased circuit clotting. With regards to inflammation we noted no significant changes in CRP, ferritin levels and other blood parameters. Conclusion Looking at our cohort of patients we concluded that HDx is safe to use with no obvious adverse effects. It seems that use of HDx is particularly helpful in improving quality of life in dialysis patients as indicated by improvement in IPOS scores. IPOS is a validated questionnaire to measure symptoms and concerns in patients with advanced illnesses. As life quality is a major concern in dialysis patients, this outcome is of particular significance. HDx was also helpful in reducing the overall burden of transfusions, iron and erythropoietin requirements. This is beneficial in overall patient health and cost burden. Based on the above we found out that HDX was safe and effective in our patient cohort, however large-scale studies will be required for more conclusive evidence.

P1102EVALUATION THE EFFICACY OF MEDIUM CUT- OFF MEMBRANE DIALYZERS AND COMPARISON WITH HIGH FLUX DIALYZERS IN CONVENTIONAL HEMODIALYSIS

Abstract Background and Aims Hemodialysis (HD) is the most widely used modality of renal replacement therapy. The high-flux dialyzers in standard hemodialysis offer numerous benefits for ESRD patients, such as, increasing the uremic toxins removal and improving patients survival, reduced patients admission and morbidity. A new class of membranes, medium cut-off (MCO) membranes, has been designed to achieve better removal capacities for middle and large middle molecules, as well as to ensure the retention of albumin in hemodialysis (HD) treatments. We evaluated the removal efficacy of Theranova® in standard HD in comparison with standard high- flux HD. Method Four stable HD patients (M/F 1/4) were included in 12-weeks small observational pilot study in HD with Theranova® 400 (sup. 1.7 m2) and Theranova® 500 (sup. 2.0 m2) dialyzers. Each patient was assessed four times, T0 with standard high flux dialyzers, T1 at 1 month, T2 at second month and T3 at third month, by measuring pre and post-HD samples of: urea, creatinine, beta2-microglobilin (B2M), myoglobin, albumin and FLC-k, FLC-λ . Data are reported as mean ± standard deviation (SD). The removal rates of uremic toxins are expressed as percentages. Results The average removal rates for the uremic toxins with standard high-flux membranes were 18.4% for B2M, 14.3% for Myoglobin, 19.8 % for FLC-k and 17.4 % for FLC-λ. The data showed a higher average removal rate for all the uremic toxins with Theranova® dialyzers for B2M, Myoglobin, FLC-k and FLC-λ (62.7%, 56.9%, 63.5%, 54.6%, respectively) during the 3 months of follow up. The using of Theranova® dialyzers in standard HD was enough to significantly decrease the pre-dialysis value of Urea (17.72 ± 2.26 vs 13.75 ± 3.75, p=0.001), Creatinine (700.50 ± 315.07 vs 570.00 ± 206.64, p=0.021), B2M (40.90 ± 11.00 vs 29.00 ± 4.64, p=0.005), FLC-k (267.25 ± 113.28 vs 225.25 ± 100.62, p=0.018), FLC-λ (324.25 ± 116.12 vs 215.23 ± 64.44, p=0.011), Myoglobin ( 199.96 ± 124.41 vs 137.00 ± 83.14, p= 0.049). Finally, albumin retention was observed with Theranova® dialyzers, between T0 and T3 it increased significantly (40.50 ± 4.79 vs 42.25 ± 4.50, p=0.0001). Conclusion Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules in mid -term report. But the long term analysis and larger number of patients is necessary to evaluate a clinical significance of this innovative therapy.

P1117EXPLORATORY COMPARISON OF DIALYSIS EFFICIENCY AT DIFFERENT DIALYSATE FLOW (QD) IN EXPANDED HEMODIALYSIS IN TWO CENTERS IN COLOMBIA

Abstract Background and Aims Dialysate flow rate (Qd) has minimal effect in removal of molecules in hemodialysis, allowing to use lower amounts of dialysate with no effect in clearance of molecules. According to recent literature, Expanded hemodialysis (HDx) improves the clearance of middle size molecules, diminishing the effect of Qd in adequacy. We found no data about clearance at different dialysate flow rates in HDx. Our aim is to evaluate the clearance of middle molecules (beta 2 microglobuline [Mβ2], interleukin-6 [IL-6], interleukin-10 [IL-10 light chains (CLL-κ -λ) with HDx at different Qd using membranes TheranovaMR in patients with body weight less than 70 Kg. Method We performed an observational retrospective analysis of clearance of Mβ2, IL-6, IL-10, CLL-κ; CLL-λ in HDx using TheranovaMR filters with Qd 400 mL/min and 500 mL/min. We performed variance analysis, T student test and Wilcoxon test. Data were extracted from an HDx multicentric trial performed in Bogotá, Colombia in 2018. Results 11 (47%) patients received Qd 400 mL/min and 12 (52.1%) patients with Qd 500ml/min. Demographic data are included in table 1. We found no differences in reduction rate of mid-molecules. (Table 2) We found that lower water consume in the Qd 400 mL/min group, with water savings of 24 Liters/patient (13824 L in 12 weeks of follow up). (Table 3) Conclusion Expanded hemodialysis seems to allow diminishing Qd rate without changes in mid-size molecules clearance.

P1084LONG TERM EVALUATION OF THE EXPANDED HEMODIALYSIS (HDX) ON DIALYSIS ADEQUACY, ANEMIA AND QUALITY OF LIFE

Abstract Background and Aims The High-Flux (HF) dialyzer in standard hemodialysis (HD) allow the removal of a wider spectrum of uremic toxin. However, the HD can remove mostly low molecular weight solutes while the HDF can remove solutes around 15kDa, so-called Middle Molecules (MM), improving morbidity and mortality by exchange volumes &amp;gt;23L per session. The new medium cut-off (MCO) filter Theranova® is designed to expand the removal of toxins up to 45kDa in HD compared to HF membranes (HemoDialysis eXpanded, HDx) even with conventional blood flows and without exchange fluid infusion. The aim of this study is to evaluate the performance of HDx and its impact on anemia and quality of life (QoL) in haemodialysis patients. Method 11 stable HDs patients were enrolled (M/F 8/3, age 70.8±9) with Qb ≤300 ml/min in a 12 months observational case-control study. Each patient was evaluated first with HF filter (T0) and then in HDx for 12 months (T12). At T0-T6-T12 were evaluated: urea, phosphate (P), beta2-microglobulin (B2m), myoglobin (Myo), free light-chains k and λ (FLC- K and FLC- λ), C-Reactive Protein (CRP), hemoglobin (Hb) and albumin as well. Furthermore Kt/V, dose of EPO, ERI and SF-36 questionnaire were evaluated at the beginning and end of observation. We treat HD patients accordingly to the KDIGO Guideline for Anemia in CKD. The values have been reported as mean ±SD. Results HDx (Qb = 275 ± 41 ml/min, TT 215 ± 21 m) shows a significant increase in KT/V (T0 1,33 ± 0,19; T12 1,57 ± 0,16; p = 0.001) with relevant RR of: Urea 73.5%; P 58.4%; B2m 66,1 % (p&amp;lt; 0.05); Myo 55,1% (p&amp;lt; 0.05); FLC-k 64.1 % (p&amp;lt; 0.05); FLC-λ 59.9% (p&amp;lt; 0.05). There is a significant reduction at 12months for PCR (Tab.1). HDx reduced ERI [T0 10.1 ± 11.2; T6 4.1 ± 5.3 (p &amp;lt;0.05); T12 6±9.8] and EPO dose [T0 8182 ± 9141; T6 3545 ± 4547 (p &amp;lt;0.05); T12 5273±8912], keeping the Hb unchanged. QoL is significantly improved (ISF: T0 27.3 ± 10.1; T12 40.2 ± 8.4 p = 0.0001) (ISM: T0 43.8 ± 14.2; T12 51.1 ± 9.8 p = 0.001). Conclusion HDx effectively removes uremic toxins up to 45kDa, even with Qb &amp;lt;300 ml/min, without reducing serum albumin and with interesting results on inflammation. Reduction of ERI and improvement of QoL are encouraging and suggest the use of HDx even in patients who cannot benefit from convective techniques because of vascular access or intolerance to high volumes of exchange.

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.

P1082COMPARISON OF THE REMOVAL OF PROTEIN-BOUND TOXINS AND LARGE MIDDLE MOLECULES WITH HIGH-FLUX PMMA AND MEDIUM CUT-OFF DIALYZERS

Abstract Background and Aims Dialytic clearance of protein-bound toxins and large middle molecules is poor by diffusive treatment and limited by high-flux hemodialysis (HD) and on-line hemodiafiltration (OL-HDF), and only a few studies have examined how to improve their removal by other extracorporeal strategies. Since 2017, there is a new generation of polymethyl methacrylate (PMMA) membranes that suppress platelet adhesion on the membrane surface improving hemocompatibility and permeability, while also maintaining adsorption properties related to conventional PMMA membranes. Expanded HD (HDx) with medium cut-off (MCO) membranes has also recently been incorporated into clinical practice and may improve the removal of uremic toxins in HD treatments. The aim of this pilot study was to compare the efficacy of a new high-flux PMMA dialyzer (Filtryzer® NF-2.1H) in a post-dilution OL-HDF session with a new MCO membrane (Theranova® 400) in a HDx session. Method In an open, cross-over, single-center, controlled, prospective clinical study, 40 adult stable HD patients were assigned to be treated by post-dilution OL-HDF with the NF-2.1H dialyzer or by HDx with the Theranova 400 dialyzer. All other dialysis parameters, including blood and dialysate flow rates, length of dialysis session, and ultrafiltration rate remained unchanged during both sessions. P-cresyl sulfate (PCS), indoxyl sulfate (IS), and kappa (κ) and lambda( λ) free light chains (FLC) reduction rates were intraindividually compared for the two dialyzer types (primary outcomes). Secondary outcomes included the kt and the reduction ratio of blood urea nitrogen, phosphate and β2 -microglobulin (β 2-m). Results The reduction ratio of protein-bound toxins ranges from 60% to 67%, with no differences between membranes (Figure). PMMA membrane achieved greater FLC reduction ratios than MCO membrane, reaching significance for λFLC (56.6% vs. 77.4%; p &amp;lt; 0.001). Conversely, β2M reduction ratio was slightly but significantly higher with MCO membrane (68.5 vs. 72.1%; p = 0.002). Small molecules removal including urea and phosphate were similar in both groups, achieving an optimal Kt with no differences between groups (61.3±9.2 Vs. 59.7±9.3; p=0.16). Albumin reduction ratio tended to be higher with PMMA membrane without reaching significance (10.1±5.9% Vs. 7.8±12.3%; p=0.17). The mean convective volume achieved with PMMA was 23.5±4.4 L. Conclusion This study suggested that new high-flux PMMA dialyzer in post-dilution OL-HDF mode might achieve better FLC reduction ratios than MCO dyalizer in HDx mode, whereas both techniques may equally remove protein-bound toxins. OL-HDF with new PMMA membranes could be a good dialysis strategy for adding convective transport to the well-known mechanisms of diffusion and absorption previously described with conventional PMMA membranes, enabling an adequate substitution volume.

P1053SHORT-TERM CLINICAL RESULTS WHEN COMPARING EXPANDED HEMODIALYSIS THERAPY VERSUS ONLINE HEMODIAFILTRATION THERAPY

Abstract Background and Aims HDx is a dialysis therapy that uses dialyzers with newly designed medium cut-off membranes (MCOs), which show a greater capacity for purification of middle molecules than conventional dialyzers and requires less technical resources than OL-HDF. However, it is not well known if HDx has comparable clinical results with OL-HDF. Therefore, the aim of this study was to evaluate the clinical differences between patients dialyzed with HDx and OL-HDF. Method A 24-week prospective study that included 43 patients between 18 and 80 years old, in OL-HDF at least 3 months before the start of the study, stratified by residual function; and randomized for HDx or HDF-OL therapy. Twenty-one patients assigned to HDx used the Theranova® 500 dialyzer with MCO membrane; and 22 patients with HDF-OL with Polyflux® 170H dialyzer. Variables related to dialysis were analyzed: blood flow rate (Qb), ultrafiltration volume (VUF), dialysis time, Kt/V, and complications; anemia [Hemoglobin (Hb), transferrin saturation (TSAT), Ferritin, erythropoietin stimulating agent (ESA) dosage (IU/week), erythropoietin resistance index (ERI), iron dose]; the bone mineral metabolism [calcium (Ca), phosphorus (Pi), product CaxPi, Paratohormone (PTH), fibroblast growth factor 23 (FGF-23)]; and healthcare resource utilization (hospitalization, cardiovascular events, infectious events and death). Results The substitution volume in the OL-HDF group was 24.4±3.2 liters. No significant differences were found in time of treatment, QB, residual diuresis or VUF. The Kt/V was similar in both groups HDx: 1.8±0.26; OL-HDF: 1.8±0.28. No significant differences in the number of adverse events during hemodialysis between the two groups. No differences in the levels of P, Ca, PTH between both groups. However, there were differences in FGF-23 at week 12 compared to baseline (HDx: -188±1351 pg/mL; OL-HDF: +218±1293 pg/mL, p=0.48). The iron dose showed no significant differences between both groups. The use of ESA was lower in the HDx group at the end of the study (HDx: 5605±7115 IU/Week; OL-HDF: 7667±5867 IU/Week), maintaining hemoglobin values stable throughout the study in both treatment groups (HDx: 11.2±1; OL-HDF: 11.7±0.8 g/dl at 24-week). Serum TSAT was comparable between the groups at all timepoints in the study. Serum ferritin levels were slightly higher in HDx group and showed an overall increase at Week 24. Both treatments were effective in maintaining pre-dialysis albumin levels. At 12 weeks (HDx: 0.06±0.47; OL-HDF: -0.01±0.26, p=0.889) and 24 weeks of treatment (HDx: -0.02±0.25; OL-HDF: - 0.02±0.34, p=0.5948) versus baseline. The assessment of rates of hospitalizations, cardiovascular events, infective episodes and death showed no substantial differences between both groups. Conclusion In our experience, HDx with Theranova® 500 is a safe and effective hemodialysis technique. A short-term HDx therapy decreases FGF23 levels and the needs of EPO compared to OL-HDF. Both techniques are similar in the other parameters analysed.

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.

P1078IMPACT OF A MEDIUM CUT-OFF DIALYZER ON SKIN AUTOFLUORESCENCE IN HAEMODIALYSIS PATIENTS

Abstract Background and Aims Advanced glycation end-products (AGEs) are middle-sized uraemic toxins that accumulate in haemodialysis (HD) patients due to increased production, impaired excretion and insufficient removal. Previous studies have reported that the use of a medium cut-off (MCO) dialyzer promotes a greater removal of larger middle molecules (such as AGEs) than conventional high-flux HD and haemodiafiltration. However, to our knowledge, there is no published evidence regarding the effect of an MCO dialyzer on skin autofluorescence (SAF), a measure of long-term tissue AGE accumulation and independent risk factor for mortality in the HD population. We aimed to investigate the impact of using an MCO dialyzer on change in SAF over time in HD patients. Method HD patients were enrolled in a prospective observational study. SAF was measured using a validated Autofluorescence Reader at baseline, 12 and 24 months. During the initial 12 months patients dialysed using high-flux polysulphone, polyarylethersulfone or polyvinylpyrrolidone dialyzers. At a variable time after 12 months patients were switched to an MCO dialyzer (Theranova; Baxter®). Forty patients who had been using the MCO dialyzer for at least 3 months were included in this analysis. Results Mean age, baseline SAF levels and time on MCO dialyzer were 63±13 years, 3.5±0.9 arbitrary units (AU) and 124±49 days, respectively. SAF increased significantly from baseline to 12 months (3.5±0.9 vs. 3.9±1.1 AU; p&amp;lt;0.0001) but tended to decrease between 12 and 24 months, after conversion to an MCO dialyzer (3.9±1.1 vs. 3.7±0.7 AU; p=0.06). Additionally, mean ΔSAF from baseline to 12 months was positive (0.41±0.68 AU) whereas ΔSAF from 12 to 24 months was negative (-0.18±0.76 AU; p=0.002 for comparison). Furthermore, SAF at 24 months correlated negatively and significantly with time on MCO dialyzer (r= -0.384; p=0.01) though second year ΔSAF (delta from 12 to 24 months) did not (r= 0.061; p=0.7). Conclusion We found in this observational study that SAF levels decreased/stabilised in HD patients after switching to an MCO dialyzer compared to the time when patients were using conventional high-flux HD and haemodiafiltration, during which SAF levels increased. Future prospective and interventional studies with larger sample sizes and longer follow-up are needed to confirm these findings and to evaluate the impact of using an MCO dialyzer on long-term outcomes, including survival.

P0635MYOGLOBIN CLEARANCE IN CVVHD USING HIGH CUT-OFF FILTER VERSUS CVVHDF WITH REGIONAL CITRAT ANTICOAGULATION: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL

Abstract Background and Aims Acute kidney injury (AKI) is frequent among critically ill patients and it is associated with high mortality. Rhabdomyolysis is a distinct cause of AKI. As myoglobin has renal toxic effects, clearance via continuous renal replacement therapy (CRRT) may be favourable. Current international guidelines recommend regional citrate anticoagulation (RCA). Clinical data comparing different modalities of CRRT addressing myoglobin clearance are lacking. Hemofiltration is recommended to eliminate myoglobin, which requires systemic anticoagulation. RCA would be impractical due to the high citrate load as a result of the higher blood flow. Continuous veno-venous hemodiafiltration (CVVHDF) is one opportunity to realize lower citrate load and maintain middle molecule clearance. Another approach may be the application of hemodialysis with high cut-off (HCO) membranes with a pore size larger than 0.01 μm in CVVHD (CVVHD-HCO). We have previously shown that CVVHD-HCO is superior to conventional high-flux dialyser regarding the clearance of β2-microglobulin. Based on this finding, we analyzed of various etiologiesre Filter lilifespan mit dem efonnummer der Virologie zum Befunderfragenmyoglobin clearance with CVVHDF compared to CVVHD-HCO with RCA. Method The present study is a prospective, randomized, single-blinded, monocentric trial. We enrolled patients from May 2017 to September 2018 in our 28-bed medical ICU at the University Hospital Leipzig. We screened 430 patients with AKI and indication for RRT for eligibility. A total of 70 patients underwent randomisation 1:1 into the intervention (CVVHD-HCO, high cut-off dialyzer Ultraflux EMiC2) and control group (CVVHDF, high-flux dialyzer Ultraflux AV1000S). The concentrations of myoglobin (17053 Dalton (Da), urea (60 Da), creatinine (113 Da), β2-microglobulin 11800 Da), interleukin 6 (IL-6, 26000 Da) and albumin (66470 Da) were measured before (pre) and after (post) the dialyzer 1, 6, 12, 24 and 48 h after initiating CRRT. We hypothesized non-inferiority of CVVHD-HCO versus CVVHDF regarding myoglobin clearance (primary end-point). Results Myoglobin clearance showed non-inferiority in the intervention group for all time points. The dialyzer in the intervention group resulted in even a better myoglobin clearance during the whole study period. (Table 1). Clearance values for urea and creatinine were equal and there was no albumin loss in both groups.β2-microglobulin clearance was significantly better in the intervention group than in the control group at all time points. The clearance of IL-6 was also better at T0 in the intervention group. The filter lifespan was 51.5 hours (CI: 44.24; 58.76) in the control group and 62.3 hours (CI 56.83; 67.7) in the intervention group (log-rank, p=0,029). Conclusion Myoglobin can be reliably cleared using both CVVHD-HCO and CVVHDF. Nevertheless, the plasma specific clearance rate of myoglobin was higher with CVVHD-HCO. High myoglobin levels are associated with AKI and higher mortality rates and on this account clearance of myoglobin represents a relevant clinical issue.

P1051ASINGLE SESSION AND WEEKLY BETA 2 MICROGLOBULIN REMOVAL DURING SHORT FREQUENT HEMODIALYSIS USING PHYSIDIA TECHNOLOGY

Abstract Background and Aims S3 Physidia monitor is a dedicated system for short frequent hemodialysis at home based on push pull dialysis mode. Clinical data is provided to show the Beta 2 microglobulin elimination, used as a model for middle molecule removal. The aim of the study is to compare Beta 2 microglobulin removal between hemodialysis systems with low dialysate flow rate and conventional hemodialysis or hemodiafiltration. Method Analyzed data is collected during multicentric clinical study performed to evaluate the safety and performances level with S3 Physidia system. This clinical investigation has been conducted in accordance with the Good Clinical Practices (Helsinki Declaration), every patient was informed by the investigator and has signed the consent form prior to the completion of the study. The project has been approved by the local Committee and authorities. Anonymized data of 10 patients (age: 55.3 +/- 12.3 years, weight: 72.8 +/- 17.2 kg) is collected during 126 dialysis sessions (blood flow rate: 293 +/- 24 ml/min, dialysate flow rate: 190 +/- 14 ml/min). The convection volume (Ultrafiltration and back filtration generated by the push pull technique) is between 1 to 8 l per session (dialyzer used: Smartflux HFP190). For each session, Beta 2 microglobulin (β2M) removal rate is calculated by using pre and post dialysis β2M blood concentrations. Post concentration is corrected by using Bergström formula to take into account the hemoconcentration and rebound. Both single session (2hours) and weekly (12 hours/week) β2m removal rates were calculated. Single session and weekly β2m removal levels are compared to published data with conventional hemodialysis or post dilution hemodiafiltration. Weekly dialysis performance is evaluated according to the standardized Kt / V (sdt) according to the Gotch calculation method. Results Using S3 daily hemodialysis, weekly dialysis diffusive performance for urea (standardized Kt / V is 2.56 +/- 0.39, higher than KDIGO recommendations for frequent dialysis (min 2.1). β2M removal rate per session is 52.9 +/- 6.6 % with pre dialytic concentration average value of 25 mg/l corresponding to 73 mg of β2M removed per session. Calculated weekly β2M removal is 438 mg. These results are compared to β2M removal obtained by standard treatment procedures (ref1) and by short frequent hemodialysis using diffusive low dialysate flow (Nx Stage system One, ref 2). During conventional hemodialysis (4h, 3 sessions per week), the β2M removal rate is between 60 to 80 % corresponding to a removal of 300 to 380 mg/week (ref 1) During high volume post dilution hemofiltration (4h, 3 sessions per week, convection &amp;gt; 20 l per session), the average β2M removal rate is 80% corresponding to a removal of 380 mg/week (ref 1) With Nx Stage device, without convective component, single session β2M removal rate is between 40 and 50 % depending on blood flow rate (maximum obtained with blood flow rate 400 ml/min) (ref 2) Ref 1: J. Potier et al, Int J Artif Organs. 2016 Nov 11;39(9):460-470 Ref 2 : M. Leclerc et al, Blood Purif 2018;46:279–285 Conclusion β2M reduction rate obtained with the S3 Physidia system is greater than 50%, removing any dowry concerning the performance of a low dialysate flow rate system. The convective component, provided by the push pull technique, must be confirmed, but these initial results are encouraging (reduction rate &amp;gt; 50% despite a relatively low blood flow rate). Due to the frequency, the quantity of β2M weekly removed is higher than that obtained with conventional treatment methods.

Medium cut-off dialyzers in a large population of hemodialysis patients in Colombia: COREXH registry.

Expanded hemodialysis (HDx) provides increased clearance of conventional and large middle molecules through innovative medium cutoff (MCO) membranes. However, there is a paucity of real‐world data regarding the benefits and safety of HDx. This large observational study evaluated outcomes among patients in Colombia undergoing HDx at a extended dialysis clinical services provider. This was a prospective single cohort study of prevalent patients who were treated with HDx; baseline information was collected from the most recent data before patients were started on HDx. Patients were followed prospectively for 1 year for changes in serum albumin and other laboratory parameters compared with the baseline. Survival, hospitalization and safety were assessed from the start of HDx. A total of 1000 patients were invited to enroll; 992 patients met the inclusion criteria for data analysis and 638 patients completed the year of follow‐up. Seventy‐four (8%) patients died during 866 patient‐years (PY) of follow‐up; the mortality rate was 8.54 deaths/100 PY (95% confidence interval [CI], 6.8‐10.7). There were 673 hospitalization events with a rate of 0.79 events/PY (95% CI, 0.73‐0.85) with 6.91 hospital days/PY (95% CI, 6.74‐7.09). The observed variability from baseline and maximum average change in mean serum albumin levels were −1.8% and −3.5%, respectively. No adverse events were related to the MCO membrane. HDx using an MCO membrane maintains stable serum albumin levels and is safe in terms of nonoccurrence of dialyzer related adverse events.