High-flux Dialysis Research Articles

Removal of middle molecules with medium cutoff dialyzer in patients on short frequent hemodialysis.

Medium cutoff (MCO) membranes for hemodialysis (HD) remove more effectively large middle molecules than high-flux (HF) membranes. In patients on in-center short frequent HD regimen (5 sessions per week, 2 hours and 30 minutes per session) the effect of MCO on middle weight uremic toxins has not been elucidated. This retrospective study included 15 patients previously performing short frequent HD with HF dialyzer (HF-HD), that were switched to short frequent HD with MCO dialyzer (MCO-HD) for 2 months, and returned to HF-HD. The primary endpoint was the predialysis concentration of α1-acid glycoprotein during the different study phases. Secondary endpoints were predialysis concentration of other middle molecules, albumin, and assessment of the quality of life using the 36-item short-form health survey (SF-36). During MCO-HD phase there was a reduction in mean ± SD α1-acid glycoprotein concentration (98.71 ± 25.2 vs. 88.6 ± 24.6 mg/dL, P = 0.107), followed by an increment 2 months after returning to HF-HD (89.18 ± 26.12 vs. 97.33 ± 31.29 mg/dL, P = 0.002); however, only the second variation was statistically significant. MCO-HD provided lower median predialysis concentration of prolactin (16 [10.2-25.6] vs. 14.1 [11.7-34.8] ng/mL, P = 0.036). Single-pool Kt/V, standard Kt/V, predialysis β2-microglobulin, myoglobin, and SF-36 questionnaire remained stable during the first two phases (pre-MCO and MCO). β2-Microglobulin increased in the post-MCO phase (20.02 ± 8.14 vs. 21.27 ± 7.64 μg/mL, P = 0.000). Mean predialysis concentration of albumin reduced significantly from pre-MCO vs. MCO phases (39.9 ± 3.7 vs. 38.3 ± 3.3 g/L, P = 0.020) and rebounded significantly from MCO vs. post-MCO phases (38.7 ± 3.1 vs. 41.3 ± 3.0 g/L, P = 0.007). In this retrospective analysis, short frequent MCO-HD promotes a reduction in prolactin, a middle weight uremic toxin, and trends toward a reduction in α1-acid glycoprotein. No patients developed hypoalbuminemia. These findings are encouraging and deserve investigation in prospective studies.

Myoglobin clearance with continuous veno-venous hemodialysis using high cutoff dialyzer versus continuous veno-venous hemodiafiltration using high-flux dialyzer: a prospective randomized controlled trial

BackgroundMyoglobin clearance in acute kidney injury requiring renal replacement therapy is important because myoglobin has direct renal toxic effects. Clinical data comparing different modalities of renal replacement therapy addressing myoglobin clearance are limited. This study aimed to compare two renal replacement modalities regarding myoglobin clearance.MethodsIn this prospective, randomized, single-blinded, single-center trial, 70 critically ill patients requiring renal replacement therapy were randomized 1:1 into an intervention arm using continuous veno-venous hemodialysis with high cutoff dialyzer and a control arm using continuous veno-venous hemodiafiltration postdilution with high-flux dialyzer. Regional citrate anticoagulation was used in both groups to maintain the extracorporeal circuit. The concentrations of myoglobin, urea, creatinine, β2-microglobulin, interleukin-6 and albumin were measured before and after the dialyzer at 1 h, 6 h, 12 h, 24 h and 48 h after initiating continuous renal replacement therapy.ResultsThirty-three patients were allocated to the control arm (CVVHDF with high-flux dialyzer) and 35 patients to the intervention arm (CVVHD with high cutoff dialyzer). Myoglobin clearance, as a primary endpoint, was significantly better in the intervention arm than in the control arm throughout the whole study period. The clearance values for urea and creatinine were higher in the control arm. There was no measurable albumin clearance in both arms. The clearance data for β2-microglobulin and interleukin-6 were non-inferior in the intervention arm compared to those for the control arm. Dialyzer lifespan was 57.0 [38.0, 72.0] hours in the control arm and 70.0 [56.75, 72.0] hours in the intervention arm (p = 0.029).ConclusionsMyoglobin clearance using continuous veno-venous hemodialysis with high cutoff dialyzer and regional citrate anticoagulation is better than that with continuous veno-venous hemodiafiltration with regional citrate anticoagulation.Trial registrationGerman Clinical Trials Registry (DRKS00012407); date of registration 23/05/2017. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012407.

Beta-2 microglobulin and all-cause mortality in the era of high-flux hemodialysis: results from theDialysis Outcomes and Practice Patterns Study.

BackgroundBeta-2 microglobulin (β2M) accumulates in hemodialysis (HD) patients, but its consequences are controversial, particularly in the current era of high-flux dialyzers. High-flux HD treatment improves β2M removal, yet β2M and other middle molecules may still contribute to adverse events. We investigated patient factors associated with serum β2M, evaluated trends in β2M levels and in hospitalizations due to dialysis-related amyloidosis (DRA), and estimated the effect of β2M on mortality.MethodsWe studied European and Japanese participants in the Dialysis Outcomes and Practice Patterns Study. Analysis of DRA-related hospitalizations spanned 1998–2018 (n = 23 976), and analysis of β2M and mortality in centers routinely measuring β2M spanned 2011–18 (n = 5332). We evaluated time trends with linear and Poisson regression and mortality with Cox regression.ResultsMedian β2M changed nonsignificantly from 2.71 to 2.65 mg/dL during 2011–18 (P = 0.87). Highest β2M tertile patients (>2.9 mg/dL) had longer dialysis vintage, higher C-reactive protein and lower urine volume than lowest tertile patients (≤2.3 mg/dL). DRA-related hospitalization rates [95% confidence interval (CI)] decreased from 1998 to 2018 from 3.10 (2.55–3.76) to 0.23 (0.13–0.42) per 100 patient-years. Compared with the lowest β2M tertile, adjusted mortality hazard ratios (95% CI) were 1.16 (0.94–1.43) and 1.38 (1.13–1.69) for the middle and highest tertiles. Mortality risk increased monotonically with β2M modeled continuously, with no indication of a threshold.ConclusionsDRA-related hospitalizations decreased over 10-fold from 1998 to 2018. Serum β2M remains positively associated with mortality, even in the current high-flux HD era.

Comparison of changes in albumin binding capacity during hemodiafiltration or hemodialysis with middle cut off membranes

Albumin is important for the transport of protein-bound substances (PBS). Albumin binding capacity (ABiC) is reduced in dialysis patients. This can contribute to worsening of uremic symptoms. It is presumed that open-porous middle cut off filters that is, HDx (Baxter-Theranova) remove high molecular substances more efficiently than conventional treatment. To evaluate HDx for the improvement of ABiC and removal of PBS, HDx was compared to hemodiafiltration (Fresenius-FX80, HDF). We included 32 chronic patients on HDF. After inclusion patients were treated with HDx for 14 days. Blood samples were drawn before/after treatments at study entry, first HDx and sixth HDx, to determine ABiC and other study parameters. ABiC improved in HDx (68.4% vs 72.4%) and HDF (69.9% vs 72.4%) without differences between both therapies. No reduction of albumin concentration during HDx treatment was observed. HDx is accepted as a safe and equally efficient therapy for removing albumin bound uremic toxins compared to HDF with high flux dialyzers.

Effect of High Flux Hemodialysis versus Hemodiafiltration on Metabolic Status in Hemodialysis Patients

Background: Hemodiafiltration (HDF) is a newly developed renal replacement therapy blood purification technology with more advantageous effects on hemodynamic stability and better removal of B2 microglobulin and phosphorous Objective: The aim of this study is to compare effect of high flux (HF), low flux (LF) dialysis membranes and hemodiafiltration (HDF) on the metabolic status in hemodialysis patients and quality of life of those patients. Patients and Methods: This study included 60 patients more than18 years old, clinically stable with end stage renal disease on regular HD for at least three years (3 yrs), selected from HD unit in (Kobry El Kobba Military Nephrology Hospital) in the period from March 2018 to September 2018. The patients were divided into three groups equally. Group I: 20 patients on low flux dialyzer, Group II: 20 patients on high flux dialyzer, Group III: 20 patients on hemodiafiltration. Results: There was a highly significant decrease in iPTH, B2 microglobulin and Phosphorous in patients received HDF (363.80±149.04, 8.79±7.22 and 4.31±0.74 respectively in comparison with patients received HF hemodialysis (540.10±242.55, 20.47±3.97and 4.58±1.07 respectively) and patients received LF hemodialysis (725.95±270.01, 36.60±7.22 and 5.73±1.34 respectively).Also, there were a highly significant increase in urea reduction ratio in HDF group compared to HF and LF groups (80.43±7.46, 76.03±9.55 and 65.81±7.42 respectively. Conclusion: Hemodiafiltration is the most effective dialysis technique than high flux and low flux dialysis membrane in removal of medium sized molecule and improvement of quality of life.

Tryptophan Removal in ESRD Patients Treated with High-Flux and Medium Cut-Off Dialyzers During Hemodialysis and Hemodiafiltration

Tryptophan Removal in ESRD Patients Treated with High-Flux and Medium Cut-Off Dialyzers During Hemodialysis and Hemodiafiltration

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.

Rhabdomyolysis-induced acute kidney injury requiring hemodialysis after a prolonged immobilization at home in 2 morbidly obese women: case reports with literature review

BackgroundRhabdomyolysis may develop into acute kidney injury (AKI), a life-threatening complication. Obese people are at risk for rhabdomyolysis due to prolonged immobilization. However, there are only a few reports of rhabdomyolysis-induced AKI due to prolonged immobilization after falls in morbidly obese people. Myoglobin is a causative compound for rhabdomyolysis-induced AKI, but the lack of treatments targeting its mechanism is a problem.Case presentationTwo morbidly obese women (body mass index > 40.0 kg/m2) who fell on the floor at home and remained in the same posture for more than 12 h developed rhabdomyolysis-induced AKI. Both patients received aggressive fluid resuscitation but required hemodialysis because of persistent oliguria. They underwent 11 and 2 intermittent hemodialysis (HD) sessions with a conventional polymethylmethacrylate (PMMA) high-flux dialyzer, respectively, and their renal functions returned to baseline after withdrawal of HD.ConclusionsWe should be aware that morbidly obese people are at risk for rhabdomyolysis-induced AKI due to prolonged immobilization, such as after falls. At present, prophylactic renal replacement therapy (RRT) is not recommended for rhabdomyolysis. We need to reevaluate whether RRT using the appropriate membranes to effectively remove myoglobin including the PMMA membrane can improve the renal outcome in patients with rhabdomyolysis-induced AKI.

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.

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.

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.

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.

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.

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.

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.

P1068LUNG ULTRASONOGRAPHY IS MORE EFFECTIVE THAN BIOIMPEDENCE OR NT-PRO BNP AT ASSESSING POST-DIALYSIS VOLUME CHANGES

Abstract Background and Aims At present, there are no precise and quantitative clinical indices for assessing fluid status in haemodialysis (HD). Existing modalities such as plasma B-type natriuretic peptide (NT-pro BNP), measurement of inferior vena cava diameter (IVCD) by ultrasound or bioimpedance spectroscopy (BIS) have limitations and do not always give quantitative measurements to guide dry weight titration. Lung ultrasonography (LUS) has emerged as a novel real-time technique to assess extravascular lung water (EVLW) on HD. Current studies comparing the above techniques often lack standardized dialysis days and timepoints for sampling volume assessment methods. This study aims to compare the performance of LUS against existing methods (NT-pro BNP, IVCD, BIS) of volume assessment in an Asian HD cohort, using a standardised protocol for sampling. The secondary aim was to measure the turnover time required for performing each volume assessment method. Method This was a prospective study of 50 chronic HD patients in a single dialysis unit. In this cohort, 34 (68%) had diabetes, and 43 (86%) were on at least 1 antihypertensive. Patients aged more than 21 years, on thrice weekly dialysis with a high flux dialyser for more than 3 months with residual urine output less then 500 ml per day were recruited. NT-pro BNP, IVCD and BIS were sampled immediately pre- and post- midweek dialysis. 28-intercostal space LUS was performed by a Nephrologist with appropriate certification immediately pre- and 30 minutes after midweek dialysis. EVLW produces lung artefacts (B-lines), which is summated into a B-line score (BLS). We also measured the time required, from performing each volume assessment methodology, to the point of result acquisition. Results Pre-HD, lung congestion was classified as mild (BLS ≤ 15) in 6 patients (12%), moderate (BLS 15 – 30) in 12 patients (24%) and severe (BLS &amp;gt; 30) in 32 patients (64%). Median BLS reduced from 46.5 (22.5 – 77.0) pre-HD to 15.5 (9.9 – 21.5) post-HD. There was a linear correlation between changes in BLS and ultrafiltration on HD, with UF 500ml approximately equal to 8.2 B-lines. There were significant but weak to moderate correlations between pre-HD LUS and BIS (r = 0.457, p = 0.004), IVCD indexed to body surface area during expiration (IVCDimax) (r = 0.371, p = 0.026) and NT-pro BNP (r = 0.406, p = 0.004). Post-HD, correlations between LUS and IVCDimax remained similar (r = 0.353, p = 0.02), but weakened with BIS (r = 0.329, p = 0.021) and became non-significant with NT-pro BNP. This was related to a paradoxical increment in NT-pro BNP and BIS overhydration values post-HD, in up to 40% of the cohort. Separately, the mean execution time for the various volume measurements were LUS: 6 ± 0.2 minutes, BIS: 5.9 ± 0.4 minutes, IVCD: 4.1 ± 0.3 minutes and the laboratory turnaround time to obtain a NT-pro BNP result was 125 ± 10.6 minutes. Conclusion LUS was able to demonstrate a linear correlation with UF volume, and may be more effective then NT-pro BNP or BIS at real-time assessment of fluid changes post-HD. The execution of LUS was no more time-consuming then BIS. LUS is hence likely to be a useful clinical tool for dry weight titration in HD patients.

P1713A CASE OF DEVASTATING BARIATRIC SURGERY-RELATED ACUTE OXALATE NEPHROPATHY FIRST DIAGNOSED AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Despite the obvious efficacy in achieving weight loss, traditional malabsorptive procedures (intestinal by-pass) used for the treatment of obesity, may be associated with enteric oxaluria. Enteric oxaluria, by causing calcium-oxalate stones and nephrocalcinosis, represents an under-recognized cause of end-stage kidney disease in patients with history of intestinal by-pass. Herein, we describe a patient with a long-standing history of intestinal by-pass who developed a devastating acute oxalate nephropathy first diagnosed after kidney transplantation. Method A white female aged 50, who started hemodialysis one year earlier because of tubule-interstitial nephritis on a kidney biopsy, and who had history of recurrent kidney stones (calcium oxalate), underwent urgent deceased-donor kidney transplantation because of exhausted vascular access for hemodialysis (tunneled CVC right giugular vein as the last resort). She had received intestinal by-pass surgery 20 yrs earlier, and had a pacemaker implantation in the left sublavian vein for AV block two years earlier. She was highly sensitized because of blood transfusions at the time of surgery. Results After transplantation, graft function had immediate recovery, serum creatinine decreasing to 2.0mg/dL (117 mmol/L) on post-operative day (POD) 3. Shortly after, serum creatinine started rising until it reached 4.0mg/dL (354mmol/L) on POD 5. Three graft biopsies (performed on POD 6, 9 and 15 post-transplant) revealed acute oxalate nephropathy ( Figure1-2 large oxalate crystals on fresh unfixed core of kidney tissue analyzed under bright field microscope using polarized light) with no sign of rejection. Serial monitoring of Luminex SAB did not reveal circulating anti-HLA donor specific antibodies. Fundus examination revealed two tiny mono-lateral retinal oxalate deposits, whereas bone biopsy did not reveal oxalate accumulation. Plasma oxalate levels were 43 mmol/L on POD 10 were urinary oxalate excretion was 29mg /day on POD 14. The patient slowly progressed to end-stage kidney disease 2-month post-transplantation despite daily high flux dialysis since POD 7, fat-free and oxalate-free diet, oral potassium and high dose pyridoxine supplements. Conclusion Patients on chronic dialysis with a previous history of bariatric surgery via intestinal by-pass may have oxalate nephropathy caused by enteric oxaluria as unknown primary renal disease. The disease may recur shortly after transplantation despite the adoption of prompt aggressive treatment for oxalate removal.

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.