Clearance Of Middle Molecules Research Articles

Online Hemodiafiltration: A New Perspective for Patients With End-Stage Renal Disease.

Introduction Online hemodiafiltration (OL-HDF) is the most effective renal replacement therapy (RRT), which allows the enhanced removal of small and large uremic toxins by combining diffusion and convective transport of solutes. Although the goal of OL-HDF is to provide greater clearance of solutes with a preference for intermediate molecules responsible for many of the complications of chronic kidney disease (CKD), the studies reported to date and their meta-analyses are conflicting in nature and do not show a significant advantage of convective therapies on patient prognosis. Materials and methods At the Clinic of Nephrology and Dialysis, University Hospital "St. Marina", Varna, Bulgaria, 41 patients were monitored in a retrospective study for a two-year period, randomized into two groups, conducting OL-HDF after dilution and hemodialysis (HD) with the aim of studying the effect of convective therapies on the clinical outcome, the achieved quality of life, and the prognosis of the patient. Results The study found a significantly higher quality of life in patients undergoing OL-HDF with significantly higher values ​​of indicators of dialysis adequacy and nutritional status, better control of the anemic syndrome with the reduction of erythropoietin doses, significantly lower frequency of episodes of intradialytic hypotension with improved recovery, and 3.6-fold lower risk of death compared with conventional dialysis. Discussion Three major randomized controlled trials have compared survival outcomes in patients receiving HD or post-dilution OL-HDF, reporting conflicting results. Meta-analyses of the published studies have also been unable to provide a clear and definitive answer regarding the potential benefits of choosing one treatment over the other. Overall mortality, anemia, phosphate control, and small molecule clearance appear to be insufficiently influenced by the treatment method. On the other hand, cardiovascular mortality, hemodynamic stability, and clearance of middle and protein-bound molecules seem to be better in patients treated with OL-HDF. Conclusions Despite the conflicting data reported so far, OL-HDF is associated with better clinical outcome and prognosis for end-stage renal disease (ESRD) patient and undoubtedly warrants extensive future study with a view to improved quality of life in the growing dialysis population.

Randomized investigation of increased dialyzer membrane hydrophilicity on hemocompatibility and performance

BackgroundHemodialyzers should efficiently eliminate small and middle molecular uremic toxins and possess exceptional hemocompatibility to improve well-being of patients with end-stage kidney disease. However, performance and hemocompatibility get compromised during treatment due to adsorption of plasma proteins to the dialyzer membrane. Increased membrane hydrophilicity reduces protein adsorption to the membrane and was implemented in the novel FX CorAL dialyzer. The present randomized controlled trial compares performance and hemocompatibility profiles of the FX CorAL dialyzer to other commonly used dialyzers applied in hemodiafiltration treatments.MethodsThis prospective, open, controlled, multicentric, interventional, crossover study randomized stable patients on post-dilution online hemodiafiltration (HDF) to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun) each for 4 weeks. Primary outcome was β2-microglobulin removal rate (β2-m RR). Non-inferiority and superiority of FX CorAL versus comparators were tested. Secondary endpoints were RR and/or clearance of small and middle molecules, and intra- and interdialytic profiles of hemocompatibility markers, with regards to complement activation, cell activation/inflammation, platelet activation and oxidative stress. Further endpoints were patient reported outcomes (PROs) and clinical safety.Results82 patients were included and 76 analyzed as intention-to-treat (ITT) population. FX CorAL showed the highest β2-m RR (76.28%), followed by FX CorDiax (75.69%) and xevonta (74.48%). Non-inferiority to both comparators and superiority to xevonta were statistically significant. Secondary endpoints related to middle molecules corroborated these results; performance for small molecules was comparable between dialyzers. Regarding intradialytic hemocompatibility, FX CorAL showed lower complement, white blood cell, and platelet activation. There were no differences in interdialytic hemocompatibility, PROs, or clinical safety.ConclusionsThe novel FX CorAL with increased membrane hydrophilicity showed strong performance and a favorable hemocompatibility profile as compared to other commonly used dialyzers in clinical practice. Further long-term investigations should examine whether the benefits of FX CorAL will translate into improved cardiovascular and mortality endpoints.Trial registrationeMPORA III registration on 19/01/2021 at ClinicalTrials.gov (NCT04714281).

#3064 Adequacy of urea and middle molecules clearance with online hemodiafiltration (HDF) for dialysate flow rates of 300 vs 500 ml/min

Abstract Background and Aims Trial cross design to determine non-inferiority in the adequacy of urea and middle molecules (B2 microglobulin, myoglobin and prolactin) clearance with 300 ml/min vs 500 ml/min of dialysate flow rate Method We have evaluated 2542 online HDF sessions (over 3 × 3 months trial cross design) in 50 patients in online HDF with sessions three times a week lasting 4 hours each. The online data from the DDM module of the Nikkiso DBB-EXA monitor were crossed, measuring urea in the dialysate effluent every 20 seconds by absorptiometry with UV light with age, sex, dialyzer, DM, BMI. In the laboratory, urea and B2 microglobulin, prolactin and mioglobin were measured at 300 and 500 ml/min, calculating the reduction rates of these toxins. We analyzed the data of 50 patients, in 25 patients, the first 3 months involved a dialysate flow rate 300 ml/min, followed by subsequent three months at 500 ml/min and vice versa for the remaining patients. They used the same dialyzer during the 3 × 3 months of the study as well as card programming. To study whether the change in dialysate flow influenced the effectiveness of dialysis, “generalized models with repeated measurements over time correcting the temporal autocorrelation with the covariance matrix AR1” were used the following parameters: kt/v, eKt/V and URR Results 23 men, 27 women, average age 70 years Kt/V.- The variables that are related to the Kt/v values throughout the sessions are: The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta = 0.01, 95% CI (−0.06, 0.08),p0.707 The effective gender (female) is statistically significant and positive (beta = 0.26, 95% CI (0.15, 0.38) p < 0.001 The effect of DM is statistically non-significant and negative (beta = −0.1, 95% CI (−0.22, 0.01) p = 0.081 The effect of period 2 is statistically non-significant and negative (beta = −0.02, 95% CI (−0.08, 0.03) p = 0.37 eKt/V.- The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta = 0.05, 95% CI (−0.02, 0.12),p0.138 The effect gender (female) is statistically significant and positive (beta = 0.22, 95% CI (0.11, 0.33) p < 0.001 The effect of DM is statistically non-significant and negative (beta = −0.10, 95% CI (−0.20, 0.01) p = 0.082 The effect of period 2 is statistically non-significant and negative (beta = −2.44e.03, 95% CI (−0.06, 0.05) p = 0.930 URR.- The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta=1.19, 95% CI (−0.22, 2.60),p0.098 The effect of gender (female) is statistically significant and positive (beta=5.52, 95% CI (3.48, 7.56) p < 0.001 Didn´t found significant difference between mean of RRb2 microglobulin, RRProlactin and RRMioglobin with dialysate flow 300 vs 500 ml/min Conclusion Urea and B2 microglobulin, myoglobin and prolactin depuration is adequate at both dialysate flow rate 500 ml/min and 300 ml/min in the evaluated patients.

#1351 Assessment of safety and efficacy of expanded hemodialysis in comparison to HDF

Abstract Background and Aims In end-stage kidney disease, solutes with a wide spectrum of molecular weight, called uremic toxins, are retained due to impaired kidney cleansing capacity. Particularly, the retention of toxins in the middle molecular weight range 15–45 kDa might negatively affects multiple organ systems and metabolic pathways. The removal of such large uraemic toxins is still a challenge. HDF has produced some results although large convective volume, optimal vascular access to increase the blood flow rate and strict water quality management are required. Medium Cut-Off, high Retention Onset membrane have been recently developed introducing the concept therapy called “expanded haemodialysis” (HDx). Furthermore, vitamin E-coated membrane has potential beneficial effects on inflammation and oxidative stress. Method A prospective longitudinal single-center study was conducted for 3 months among 18 chronic haemodialysis patients. Patients were randomly assigned into either HDF with high flux membrane or HDx with Theranova or ViE-X membrane. The primary goal was to assess albumin loss among the three types of dialyzers. Secondary goals included assessment of depurative efficacy for uraemic toxins and clinical outcomes. Throughout the treatment, a proportional part of the dialysis fluid was collected to quantify albumin loss. Blood samples were taken before and after dialysis session in order to calculate the Removal Ratio and at two different intradialytic timepoints from arterial and venous line of the circuit in order to calculate instantaneous clearance. Results Mean albumin loss was significantly higher in patients undergoing HDx with Theranova membrane (ANOVA, p<0.001) without any difference in serum albumin concentration among the three groups. Instantaneous clearance of small and middle molecules was significantly higher in patients undergoing HDF, but we didn't find differences in removal ratio. Reduction of Erythropoietin resistance index was observed in patients treated with ViE-X membrane but it was related to their lower dialysis vintage. Conclusion HDx with Theranova membrane was associated with higher albumin loss without any effect on pre-dialysis serum albumin. Moreover, patients treated Theranova membrane, in the presence lower Qb, lower convective dose and lower instantaneous clearance reached same dialysis efficacy compared to HDF.

Hydrophilic Modification of Dialysis Membranes Sustains Middle Molecule Removal and Filtration Characteristics.

While efficient removal of uremic toxins and accumulated water is pivotal for the well-being of dialysis patients, protein adsorption to the dialyzer membrane reduces the performance of a dialyzer. Hydrophilic membrane modification with polyvinylpyrrolidone (PVP) has been shown to reduce protein adsorption and to stabilize membrane permeability. In this study we compared middle molecule clearance and filtration performance of nine polysulfone-, polyethersulfone-, and cellulose-based dialyzers over time. Protein adsorption was simulated in recirculation experiments, while β2-microglobulin clearance as well as transmembrane pressure (TMP) and filtrate flow were determined over time. The results of this study showed that β2-microglobulin clearance (-7.2 mL/min/m2) and filtrate flow (-54.4 mL/min) decreased strongly during the first 30 min and slowly afterwards (-0.7 mL/min/m2 and -6.8 mL/min, respectively, for the next 30 min); the TMP increase (+37.2 mmHg and +8.6 mmHg, respectively) showed comparable kinetics. Across all tested dialyzers, the dialyzer with a hydrophilic modified membrane (FX CorAL) had the highest β2-microglobulin clearance after protein fouling and the most stable filtration characteristics. In conclusion, hydrophilic membrane modification with PVP stabilizes the removal capacity of middle molecules and filtration performance over time. Such dialyzers may have benefits during hemodiafiltration treatments which aim to achieve high exchange volumes.

Application of the second-order fluid model to estimate factors affecting clearance of small and middle uremic molecules using combined ultrafiltration and diffusion processes

Uremic solute transport in a hollow fiber dialyzer is investigated theoretically with combined ultrafiltration and diffusion with the assumption of uniform ultrafiltration velocity and other standard assumptions. A numerical solution for concentration profiles in the blood compartment is obtained by using an implicit finite difference scheme implemented with MATLAB R2018a. The resulting system of linear equations is solved using another Matlab script implementing the Gauss–Seidel method. Uremic clearance of three solutes viz. urea, creatinine, and vitamin B-12 are considered. Different factors affecting Cl were observed and discussed in detail. Those factors include operating conditions (inlet blood flow rate, ultrafiltration velocity, etc.), dialyzer geometry (length, radius, number of fibers), and fluid parameters. The solute clearance can be maximized for a suitable set of values of these parameters.

Kinetics of small and middle molecule clearance during continuous hemodialysis

Regional citrate anticoagulation (RCA) enables prolonged continuous kidney replacement therapy (CKRT) filter lifespan. However, membrane diffusive performance might progressively decrease and remain unnoticed. We prospectively evaluated the kinetics of solute clearance and factors associated with decreased membrane performance in 135 consecutive CKRT-RCA circuits (35 patients). We recorded baseline patients’ characteristics and clinical signs of decreased membrane performance. We calculated effluent/serum ratios (ESR) as well as respective clearances for urea, creatinine and β2-microglobuline at 12, 24, 48 and 72 h after circuit initiation. Using mixed-effects logistic regression model analyses, we assessed the effect of time on those values and determined independent predictors of decreased membrane performance as defined by an ESR for urea < 0.81. We observed a minor but statistically significant decrease in both ESR and solute clearance across the duration of therapy for all three solutes. We observed decreased membrane performance in 31 (23%) circuits while clinical signs were present in 19 (14.1%). The risk of decreased membrane performance significantly increased over time: 1.8% at T1 (p = 0.16); 7.3% at T2 (p = 0.01); 15.7% at T3 (p = 0.001) and 16.4% at T4 (p < 0.003). Four factors present within 24 h of circuit initiation were independently associated with decreased membrane performance: arterial blood bicarbonate level (OR 1.50; p < 0.001), activated partial thromboplastin time (aPTT; OR = 0.93; p = 0.02), fibrinogen level (OR 6.40; p = 0.03) and Charlson score (OR 0.10; p < 0.01). COVID-19 infection was not associated with increased risk of decreased membrane performance. Regular monitoring of ESR might be appropriate in selected patients undergoing CKRT.

#3205 A 2-YEAR STUDY FOR CHANGE OF PLASMA BIOMARKERS INCLUDING LARGER MIDDLE MOLECULES IN DIALYTIC PATIENTS USING DIALYZERS WITH MEDIUM CUT-OFF MEMBRANES

Abstract Background and Aims Uremic toxins with middle molecular weight usually develop uremic symptoms. The larger middle molecules are regarded as causative molecules of uremic symptoms. Medium cut-off (MCO) membrane newly developed can remove larger middle molecules which can be not removed through high flux membrane and hemodiafiltration. Larger middle molecules are mainly related to cardiovascular complications. Therefore, long-term use of MCO membrane may have beneficial effects in dialytic patients, in terms of lowering concentrations of larger middle molecules associated with cardiovascular complications. Now, we report interesting 2-year results of long-term use of MCO membrane in dialytic patients. Method Thirty-four patients undergoing hemodialysis were prospectively analyzed during 24 months. We randomly divided enrolled patients into two groups: control and MCO group. Patients in the control group used dialyzer with high flux membrane and patients in MCO group used MCO membrane. We measured plasma levels of biomarkers with 3 or 6-month to investigate efficacy of the MCO membrane for small (3-month interval) to larger middle molecules (6-month interval). Particularly, we performed comparative analysis with larger middle molecules in both groups. We calculated reduction ratio of biomarkers per one session at 24-month. Results The levels of larger middle molecules at baseline did not show significant difference between two groups. However, compared with the control group, plasma sclerostin levels at 6-month and 12-month in MCO group did not increased significantly compared to baseline levels. Plasma sclerostin were lower in MCO group throughout 2 year, but the significant difference of plasma sclerostin levels between two groups unfortunately disappeared after 12 months. The levels of other biomarkers including FGF23, leptin and GDF15, also did not show significant difference between two groups. However, β2MG levels in MCO group compared to control group decreased significantly throughout 2 years (MCO group: 18-month, p = 0.01 and 24-month, p &amp;lt;0.001, respectively; control group: 18-month, p = 0.003 and 24-month, p &amp;lt;0.067, respectively). Interestingly, even in MCO group, there was no statically significant decrease in total protein and albumin levels after 24 months (p = 0.429 and p = 0.101, respectively) (Figure 1). The reduction ratio of larger middle molecules compared to small molecules per one session prominently increased in MCO group (sclerostin, p &amp;lt; 0.001; GDF15, p &amp;lt;0.001; FGF23, p &amp;lt;0.01; RBP4, p &amp;lt;0.01; phosphate, p = 0.821; calcium, p = 0.827; CRP, p = 0.729 and β2MG, p = 0.286, respectively) (Figure 2). Conclusion Conclusively, in MCO group, the significant change of plasma sclerostin associated with cardiovascular complications after 12 months disappeared. However, in MCO group compared to control group, there was a continuous decrease of β2MG and RBP4 throughout study period. In addition, the clearance of larger middle molecules is also prominently high in MCO group. Interestingly, there were also no significant differences of albumin between 24-month and baseline in MCO group. Therefore, the MCO membrane can be a good tool for controlling uremic symptoms or sings without protein loss even when used for a relatively long time in dialytic patients.

On the balance between albumin loss and removal of middle molecules in dialyzers

Tuning the pore size distribution of hemodialysis membranes is essential for the membrane’s selectivity and significantly affects the quality of the dialysis treatment. Tailoring the membrane’s molecular weight cut-off appropriately balances the removal of middle-molecular-weight uremic toxins while avoiding albumin loss. This undesirable albumin loss is a potential side effect and concern for clinical use when aiming at increased removal of middle molecular weight molecules (middle molecules). It is hypothesized that control of the position of a narrow pore size distribution allows middle molecule removal while simultaneously counteracting the unwanted albumin loss. This study presents a comprehensive ex-vivo methodology and novel data on the balance of the clearance of middle molecules and albumin loss at different blood and dialysate flow rates using novel dialyzers. The outcomes hold significance for dialysis therapy, while the insights acquired have broader implications for the selectivity of ultrafiltration membranes.The Theranova dialyzer shows the largest clearance for small-middle molecules. Phylther stands out with higher removal of the middle molecule YKL-40 than the other dialyzers but exhibits a significant albumin loss. Theranova demonstrates the best compromise between low albumin loss and good clearances of middle molecules.

A Review of Residual Kidney Function in Peritoneal Dialysis Patients.

Residual kidney function (RKF) has been associated with better survival, less morbidity, and improved quality of life in peritoneal dialysis (PD) patients. Since higher peritoneal clearance does not lead to better outcomes, more emphasis should be put on preserving kidney function. Many other benefits have been reported, including better volume and blood pressure control, better nutritional status, lower rates of PD peritonitis, preserved erythropoietin and vitamin D production, middle molecule clearance, lower Left Ventricular Hypertrophy, and better serum phosphate level. The most practical method of assessing RKF is the mean of 24-h urinary urea and creatinine clearance. Incremental PD prescription is an ideal option to supplement RKF in PD patients, which also offers more flexibility to the patient and, possibly, improved adherence. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be used when possible in PD patients to preserve RKF. Loop diuretics are underutilized in PD patients despite providing an additional means of maintaining fluid balance and reducing the need for higher glucose-containing PD solutions. In this paper, we outline the importance of RKF in PD patients and the different strategies for its preservation.

Iron status and anemia control are related to peritoneal membrane properties in peritoneally dialyzed patients.

Characteristics of peritoneal membrane is unique and individually different in peritoneal dialysis patients. Relationship between specific nature of peritoneal transport, anemia and inflammation has not yet been extensively studied. We attempted to outline the complex interplay of several biomarkers of iron status and their association with peritoneal transport, degree of inflammation and residual renal function. A total of 58 patients treated with peritoneal dialysis either CAPD or APD for at least 3 months were enrolled in this study. Full blood count, traditional markers of iron status (transferrin saturation-TSAT and ferritin), serum erythroferrone-ERFE, soluble transferrin receptor (sTfR), hepcidin, zonulin, growth differentiation factor -15 (GDF15), IL-16, hsCRP and hypoxia-inducible factor-α (HIF-1-α; in serum and dialysate) were measured using commercially available tests. We also performed Peritoneal Equilibrium Test and assessed GFR level. Hb levels above 10 g/dL was found in 74% of patients. Hb levels positively correlated with residual renal function and nutritional status. Adequate iron status was diagnosed in 69% of subjects, only in 9% of patients, criteria for absolute iron deficiency were met. Serum ERFE correlated inversely with hepcidin levels but was not associated with erythropoietin stimulating agent dose. Peritoneal transport had strong correlation with dialysate sTfR (p < 0.05), dialysate hepcidin (p < 0.05), dialysate GDF15 (p < 0.01) and dialysate zonulin (p < 0.001) levels, as well as serum IL6 (p = 0.03), serum hs-CRP (p = 0.04) and dialysate hs-CRP (p = 0.04). Residual kidney function contributes considerably to better control of anemia. Various degree of inflammation is inherent to PD patients. Additionally, fast-average peritoneal transport is associated with greater degree of inflammation and higher concentration of markers of iron status, GDF15 and zonulin in dialysate. This finding may indicate more effective clearance of higher-range middle molecules in fast-average transporters. The role of ERFE as a marker of erythropoiesis in PD patients requires further investigation.

EE96 Budget-Impact Analysis of Adopting Expanded Hemodialysis (HDX) Via Theranova® in Korea

HD (Hemodialysis) is the dominant modality among ESRD patients in Korea, so the role of dialyzer is quite important for treatment outcomes. Theranova® (dialyzer of expanded hemodialysis, HDx) is a medium cut-off dialyzer that allows for better clearance of large middle molecules than traditional high-flux dialyzers. Compared to high flux HD, HDx via Theranova® has been associated with reduced treatments for anemia and lower risk of all-cause and cardiovascular hospitalization. This budget impact analysis evaluates healthcare costs aligned with clinical factor between Theranova® and conventional hemodialysis (HD) with a high-flux dialyzer in Korea.

Economic evaluation of expanded hemodialysis with the Theranova 400 dialyzer: A post hoc evaluation of a randomized clinical trial in the United States.

IntroductionThe Theranova 400 is a medium cut‐off dialyzer that allows for superior clearance of larger middle molecules than traditional high‐flux dialyzers. This study evaluates the association of expanded hemodialysis (HDx) using the Theranova dialyzer versus conventional hemodialysis (HD) with a high‐flux dialyzer on hospitalization rates and healthcare costs as compared to conventional HD in a post hoc analysis of a randomized controlled trial.MethodsIn a non‐concealed, 24‐week clinical trial, maintenance HD patients were randomized to receive treatment with either Theranova 400 or a similar size high‐flux dialyzer. Hospitalization rate and average length of stay were calculated from trial data. Use of erythropoiesis‐stimulating agents and iron were assumed to be equal and therefore excluded from the model. Average cost per inpatient day was obtained from a publicly available published source. Probabilistic sensitivity analyses were conducted to account for variability in model inputs.FindingsThere were 86 patients (389 patient‐months) in the Theranova group and 85 patients (366 patient‐months) in the high‐flux HD group. All‐cause hospitalization rate was 45% lower with Theranova compared to high‐flux HD (IRR = 0.55; p = 0.05). Average annual estimated cost of hospitalization was $6098 lower with Theranova compared to high‐flux HD. Compared to high‐flux HD, average annual estimated cost associated with Theranova use was $4772 lower per patient. Hospitalization rate and hospital length of stay were the main drivers of cost.ConclusionsUse of the Theranova dialyzer is associated with lower estimated costs of care among maintenance HD patients, driven by fewer hospitalization events.

Clinical Outcomes With Medium Cut-Off Versus High-Flux Hemodialysis Membranes: A Systematic Review and Meta-Analysis.

Background:A novel medium cut-off (MCO) dialyzer (Theranova, Baxter Healthcare, Deerfield, IL, USA) enhances large middle molecule clearance while retaining selectivity for molecules >45 000 Da.Objective:We undertook a systematic review and meta-analysis evaluating clinical outcomes with MCO vs high-flux membranes.Methods:We searched MEDLINE, EMBASE, CINAHL, Cochrane Library, and Web of Science through July 2020, and gray literature sources from 2017. We included randomized (RS) and nonrandomized studies (NRS) comparing MCO and high-flux membranes in adults receiving maintenance hemodialysis. Pairs of reviewers performed study selection, data extraction, and risk of bias assessment in duplicate. We conducted random-effects pairwise meta-analyses to pool results across studies and used the Grading of Recommendations Assessment, Development and Evaluation approach to assess evidence certainty.Results:We identified 22 eligible studies (6 RS, 16 NRS; N = 1811 patients; patient-years = 1546). The MCO dialyzer improved (estimate; 95% confidence interval [CI]; certainty rating) quality of life (mean difference [MD] = 16.7/100 points; 6.9 to 26.4; moderate), Kidney Disease Quality of Life Instrument (KDQOL) subscales—burden (MD = 4.0; 1.1 to 6.9; moderate) and effects (MD = 5.4; 3.2 to 7.6; moderate), pruritus (MD = −4.4; −7.1 to −1.7; moderate), recovery time (MD = −420 minutes; −541 to −299; high), and restless legs syndrome (odds ratio = 0.39; 0.29 to 0.53; moderate). There was little to no difference in all-cause mortality (risk difference = −0.4%; −2.8 to 2.1; moderate) and serious adverse events (rate ratio = 0.63; 0.38 to 1.04; low). MCO dialysis reduced hospitalization (rate ratio = 0.48; 0.27 to 0.84; low), infection (rate ratio = 0.38; 0.17 to 0.85; moderate), hospitalization days (MD = −1.5 days; 95% CI, −2.22 to −0.78; moderate), erythropoiesis resistance index (MD = −2.92 U/kg/week/g/L; 95% CI, −4.25 to −1.6; moderate) and cumulative iron use over 12 weeks (MD = −293 mg; 95% CI, −368 to −218; moderate). We found with low certainty that MCO dialysis had little to no effect on KDQOL symptoms/problem list, pain, and physical health and moderate certainty that MCO dialysis likely has no effect on the KDQOL mental health composite.Conclusions:We found with predominantly moderate certainty that the MCO dialyzer improves several patient-important outcomes with no apparent risks or harms. More definitive studies are needed to better quantify the effects of MCO membranes on mortality, hospitalization, and other rare events.

Update on Pediatric Hemodialysis Adequacy.

The use of high reflux dialyzers to achieve a Kt/Vurea above 1.2 did not improve patient survival in most literature reports. After an electronic search in many sites, guidelines, systematic reviews, and review articles (cited references): We recommend (1) using the equilibrated double-pool, weekly rather than per session, Kt/Vurea, (2) Use of UF-dry weight to avoid V changes, (3) consider protein catabolic Rate (4) Use of double pool to avoid urea generation rebound effect. Beyond the urea model, other recommended parameters include the middle molecule clearance and patient clinical data as blood pressure control, normal ventricular morphology, and function, absence of anemia, bone mineral disease, vascular calcifications, good nutrition and growth, long-lasting vascular access, less intra-dialysis hypotension, fewer hospitalizations related to complications as infection, long-term patient survival with better life quality. All mentioned parameters are the good markers for adequate dialysis. Since (1) frequent short and (or) slow long dialysis sessions show better solute clearance and hemodynamic stability associated with better control of cardiovascular and bone disease, anemia, nutrition, and growth with better quality of life and survival. (2) The spare in the cost of the antihypertensive medications, erythroid-stimulating drugs, phosphate binders, and frequent hospitalization, compensates for the high dialysis cost. (3) The use of some advisable techniques can minimize access trauma; therefore, HD Model can be changeable according to each patient's clinical and biochemical follow-up dialysis adequacy progress pattern.

Effects of Medium Cut-Off Versus High-Flux Hemodialysis Membranes on Biomarkers: A Systematic Review and Meta-Analysis.

Background:Medium cut-off (MCO) membranes enhance large middle-molecule clearance while selectively retaining molecules >45 000 Da.Objectives:We undertook a systematic review and meta-analysis comparing the effects of MCO versus high-flux membranes on biomarkers.Methods:We searched MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science from January 2015 to July 2020, and gray literature sources from 2017. We included randomized (RS) and nonrandomized studies (NRS) comparing MCO and high-flux membranes in adults (>18 years) receiving maintenance hemodialysis. We performed study selection, data extraction, and quality appraisals in duplicate and used the Grading of Recommendations Assessment, Development, and Evaluation framework. Outcomes included solute removal (plasma clearance or dialysate quantitation), reduction ratios, and predialysis serum concentrations for a range of prespecified large middle molecules.Results:We identified 26 eligible studies (10 RS and 16 NRS; N = 1883 patients; patient-years = 1366.3). The mean difference (MD) for albumin removal was 2.31 g per session (95% confidence interval [CI], 2.79 to 1.83; high certainty), with a reduction in predialysis albumin of −0.12 g/dl (95% CI, −0.16 to −0.07; I2 = 0%; high certainty) in the first 24 weeks, returning to normal (MD = −0.02 g/dl, 95% CI, −0.07 to −0.03; I2 = 56%; high certainty) after 24 weeks. We also found with high certainty that MCO dialysis resulted in a large increase (standardized mean difference [SMD]> 2.0 for all) in β2-microglobulin, κ- and λ-free light chains, and myoglobin removal, resulting in moderate (SMD > 0.5) to large (SMD > 0.8) reductions in predialysis concentrations for all of these solutes. Medium cut-off dialysis increased the reduction ratio for tumor necrosis factor-alpha (TNF-α) by 7.7% (95% CI, 4.7 to 10.6; moderate certainty), and reduced predialysis TNF-α by SMD −0.48 (95% CI, −0.91 to −0.04; moderate certainty). We found with moderate certainty that MCO dialysis had little to no effect on predialysis interleukin-6 (IL-6) plasma concentrations. Medium cut-off dialysis reduced mRNA expression of TNF-α and IL-6 in peripheral leukocytes by MD −15% (95% CI, −19.6 to −10.4; moderate certainty) and −8.8% (95% CI, −10.2 to −7.4; moderate certainty), respectively.Conclusion:Medium cut-off dialysis increases the clearance of a wide range of large middle molecules and likely reduces inflammatory mediators with a concomitant transient reduction in serum albumin concentration. The net effect of MCO dialysis on large middle molecules could translate into important clinical effects.

FC 093EFFICACY OF EXPANDED HEMODIALYSIS AT DIFFERENT DIALYSATE FLOWS

Abstract Background and Aims Expanded hemodialysis (HDx) is based on hollow fibre dialyzer focused on improving the clearance of middle molecules as a target for uremia treatment. According to in vitro and in vivo results, High cut off filters have high enough clearance to allow diminishing of dialysate flow. Our aim is to compare clearance of middle molecules at different dialysate flow (Qd) in HDx with TheranovaMR membranes. Our aim was to Evaluate efficacy of MCO dialyzer in terms of Kt/V and phosphorus levels at different prescribed dialysate flows (Qd) 400 vs 500 ml/min in HD patients from 10 renal clinics in Colombia. Method We performed a Prospective, observational, multicenter cohort study. Prevalent adult HD patients (&amp;gt;90 days), with weight lower or equal to 70 Kg, were included between September to November 2017 and prospectively followed for one year with routine monthly blood tests for HD adequacy and registered at both Qd groups at 1, 3, 6, 9 and 12 months. A mixed-model repeated measures analysis (MMRM) was performed to identify statistical differences over time. Socio-demographic and clinical characteristics of all patients were summarized descriptively by Qd. Results 462 patients were included: 127 with Qd 400 mL/min. We did not find statistically significative differences in serum levels of albumin, hemoglobin, calcium or phosphorus when comparing Qd 400ml/min vs 500 ml/min. We found statistically higher Kt/V in Qd 400 mL/min patients. (Table 2). In a sustainability analysis, part of Blue Planet dialysis research group, we calculated important savings in water waste in Qd 400 mL/min group. Conclusion MCO dialyzers are at least as effective in reaching HD adequacy parameters (Kt/V, PO4) at Qd 400 as 500 mL/min with interesting savings of potable water: 24 Liters were saved in each session per patient.

FC 134WATER SAVING COMPARISON AT DIFFERENT DIALYSATE FLOWS IN EXPANDED HEMODIALYSIS

Abstract Background and Aims Expanded hemodialysis (HDx) improves clearance of middle molecules as a target for uremia treatment. According to previously published results, high cut off filters have high enough clearance to allow diminishing of dialysate flow (Qd) without detrimental in HD adequacy outcomes with less water waste. According to World Health Organization (WHO), globally, almost 800 million people lack access to safe water and 2.5 billion lack access to optimal sanitation. Is our duty to search for ways to avoid water waste. Our aim is to describe the differences in water use between HDX patients receiving Qd 400 mL/min (Group 1) vs 500 ml/min (group 2) in HD patients from 10 renal clinics in Colombia as an alternative to reduce water waste in chronic HD as a strategy from Blue Planet Dialysis initiatives. Method We performed a Sub-analysis of CORHEX Study: We calculated water use at different Qd from our database: prospective, multicentre, observational cohort study of 992 adult patients undergoing chronic HD from 12 renal clinics in Colombia who were switched from high-flux HD to MCO therapy and observed for 12 months. All patients were prescribed with HDX three times a week for a minimum of 4 hours. We analysed patients with weight lower than 70 Kg at different Qd prescriptions to calculate water use at different Qd prescriptions and performed a prediction analysis, adjusting to Qd 400 mL/min, the whole potential population with weight lower than 70 Kg. Results 462 patients with weight lower than 70 Kg were analysed, 127 patients received Qd 400 mL/min. When diminishing Qd from 500 to 400 mL/min, 24 litres were saved per session per patient without detriment of middle molecule clearance. There were no differences in adequacy HD parameters between Qd prescriptions (Table 1 and 2). Conclusion HDX allows lowering of Qd to 400 mL/min without harm for patients and with remarkable savings of potable water: 24 Litres were saved in each session per patient that can be translated in almost 3500 Litres of water each year by patient which is enough for one year for 47 adults. (Based on the WHO minimum for basic health protection of at least 20 L per person/day) (2). We consider our results especially relevant since the World Health Organization estimates that within the next 5 years, over 50% of world population could reside in geographies lacking sufficient access to water. We hope that our results from the Blue Planet dialysis research group, alongside with Dr. Agar`s and Dr. Barraclough`s green nephrology initiatives, can help educate the nephrology community on the ecological impact of dialysis and can present an innovative solution to offer HD therapy even in countries suffering from limited access to potable water.

Changes in plasma sclerostin level associated with use of a medium cut-off dialyzer in end-stage renal disease.

BackgroundLarger middle molecules are important substances associated with cardiovascular complications in end- stage renal disease. Unfortunately, larger middle molecules are not reliably removed by a high -flux dialyzer. A medium cut-off (MCO) membrane could effectively remove larger middle molecules. This study aimed to identify the long-term effect of the MCO membrane for changes of larger middle molecules.MethodsThirty-four patients were prospectively analyzed for 12 months. The enrolled patients were divided into control and MCO groups. We measured the plasma levels of growth differentiation factor 15, sclerostin, and fibroblast growth factor 23 in larger middle molecules and those of biomarkers including small solutes. Single-pool Kt/V (spKt/V) and reduction ratios also were evaluated.ResultsPlasma sclerostin did not increase significantly in patients using the MCO dialyzer (135.294 [–637.726 to 908.314], p = 0.715). And there was a significant difference in change of plasma sclerostin level between the two groups (–1,646.916 [–3,015.150 to –278.682], p = 0.033). Furthermore, a negative association between calcium and sclerostin was not observed in the MCO group (r = –0.142, p = 0.587). Solute clearance of larger middle molecules in the MCO group was significantly higher. Moreover, spKt/V values for patients in the MCO group were significantly increased without albumin loss. Values are presented as mean (95% confidence interval [CI]) or adjusted mean (95% CI).ConclusionThe MCO dialyzer can increase dialytic adequacy and suppress the increase in plasma sclerostin level without significant albumin loss in patients with end-stage renal disease.

Impact of Medium Cut-Off Dialyzers on Patient-Reported Outcomes: COREXH Registry

Introduction: A new generation of hemodialysis (HD) membranes called medium cut-off (MCO) membranes possesses enhanced capacities for middle molecule clearance, which have been associated with adverse outcomes in this population. These improvements could potentially positively impact patient-reported outcomes (PROs). Objective: The objective of this study was to evaluate the impact of MCO membranes on PROs in a cohort of HD patients in Colombia. Methods: This was a prospective, multicenter, observational cohort study of 992 patients from 12 renal clinics in Colombia who were switched from high-flux HD to MCO therapy and observed for 12 months. Changes in Kidney Disease Quality of Life 36-Item Short Form Survey (KDQoL-SF36) domains, Dialysis Symptom Index (DSI), and restless legs syndrome (RLS) 12 months after switching to MCO membranes were compared with time on high-flux membranes. Repeated measures of ANOVA were used to evaluate changes in KDQoL-SF36 scores; severity scoring was used to assess DSI changes over time; Cochran’s Q test was used to evaluate changes in frequency of diagnostic criteria of RLS. Results: During 12 months of follow-up, 3 of 5 KDQoL-SF36 domains improved compared with baseline: symptoms (p < 0.0001), effects of kidney disease (p < 0.0001), and burden of kidney disease (p < 0.001). The proportion of patients diagnosed with RLS significantly decreased from 22.1% at baseline to 10% at 12 months (p < 0.0001). No significant differences in the number of symptoms (DSI, p = 0.1) were observed, although their severity decreased (p = 0.009). Conclusions: In conventional HD patients, the expanded clearance of large middle molecules with MCO-HD membranes was associated with higher health-related quality of life scores and a decrease in the prevalence of RLS.