Distinct Solute Removal Patterns by Similar Surface High-Flux Membranes in Haemodiafiltration: The Adsorption Point of View.

INTRODUCTION: Haemodialysis (HD) allow depuration of uraemic toxins by diffusion, convection, and adsorption. Online haemodiafiltration (HDF) treatments add high convection to enhance removal. There are no prior studies on the relationship between convection and adsorption in HD membranes. The possible benefits conferred by intrinsic adsorption on protein-bound uraemic toxins (PBUTs) removal are unknown. METHODS: Twenty-two patients underwent their second 3-days per week HD sessions with randomly selected haemodialysers (polysulfone, polymethylmethacrylate, cellulose triacetate, and polyamide copolymer) in high-flux HD and HDF. Blood samples were taken at the beginning and at the end of the treatment to assess the reduction ratio (RR) in a wide range of molecular weight uraemic toxins. A mid-range removal score (GRS) was also calculated. An elution protocol was implemented to quantify the amount of adsorbed mass (Mads) for each molecule in every dialyser. RESULTS: All synthetic membranes achieved higher RR for all toxins when used in HDF, specially the polysulfone haemodialyser, resulting in a GRS = 0.66 ± 0.06 (p < 0.001 vs. cellulose triacetate and polyamide membranes). Adsorption was slightly enhanced by convection for all membranes. The polymethylmethacrylate membrane showed expected substantial adsorption of ß2-microglobulin (MadsHDF = 3.5 ± 2.1 mg vs. MadsHD = 2.1 ± 0.9 mg, p = 0.511), whereas total protein adsorption was pronounced in the cellulose triacetate membrane (MadsHDF = 427.2 ± 207.9 mg vs. MadsHD = 274.7 ± 138.3 mg, p = 0.586) without enhanced PBUT removal. DISCUSSION/CONCLUSION: Convection improves removal and slightly increases adsorption. Adsorbed proteins do not lead to enhanced PBUTs depuration and limit membrane efficiency due to fouling. Selection of the correct membrane for convective therapies is mandatory to optimize removal efficiency.

Efficacy and safety of the Clearum dialyzer.

The Clearum dialyzer, built by Medtronic, became commercially available in several European countries in 2020, but there are still no reports of in vivo data. The aim of this study was to evaluate the efficacy and risk of hypoalbuminemia of this dialyzer compared with previously evaluated hemodialysis (HD), expanded hemodialysis (HDx), and postdilution hemodiafiltration (HDF) treatments. A prospective study was carried out in 15 patients. Each patient underwent seven dialysis sessions: FX80 Cordiax in HD, Clearum HS17 in HD, Phylther 17-SD in HDx, Theranova 400 in HDx, Phylther 17-G in postdilution HDF, Clearum HS17 in postdilution HDF, and FX80 Cordiax in postdilution HDF. The reduction ratios of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. Dialysate albumin loss was also measured. Comparison of dialysis techniques revealed no differences between small molecules, but HDx and HDF were significantly higher than HD with medium and large molecular weights. The Clearum dialyzer in HDF obtained similar results to FX80 Cordiax in HDF, was slightly superior to Phylther 17-G in HDF, and was statistically superior to both dialyzers in HDx. Albumin losses with the Clearum dialyzer were among the lowest, both in HD and HDF treatments. The highest global removal score (GRS) values were obtained with the helixone and Clearum dialyzers in HDF, with similar results both in HD and HDF. In addition, the GRS values with HDx treatments were statistically significantly higher than those with HD. The new Clearum dialyzer has excellent behavior and tolerance in HD and HDF. Its adequate permeability has been proven with its maximal performance in HDF, which could represent an upgrade versus its predecessor polyphenylene dialyzers.

Cardiovascular Risk Comparison between Expanded Hemodialysis Using Theranova and Online Hemodiafiltration (CARTOON): A Multicenter Randomized Controlled Trial.

Expanded hemodialysis (HDx) with medium cutoff (MCO) membranes, which remove middle-to-large molecules well, may be a good option to replace online hemodiafiltration (online-HDF). To provide more evidence, this randomized controlled trial compared several cardiovascular parameters between patients undergoing HDx and online-HDF. Eighty patients undergoing thrice-weekly hemodialysis were randomly assigned to receive either HDx with a Theranova membrane (n = 43) or online-HDF (n = 37). The primary endpoints were changes in brachial-ankle pulse wave velocity (baPWV), echocardiographic parameters, and coronary artery calcium (CAC) scores over 1 year, and the secondary endpoints included blood cardiovascular biomarkers, mortality, and patient-reported outcomes. A linear mixed model and log-rank test were used to estimate the group differences. 65 patients had completed the trial. The changes in baPWV and echocardiographic parameters did not differ between the two groups. The CAC scores remained stable in the online-HDF group, whereas an increasing trend was shown in the HDx group (P = 0.012). Other endpoints, including cardiovascular and all-cause mortalities, were similar between the two groups. The changes in cardiovascular parameters did not differ between HDx with an MCO membrane and online-HDF. However, attention may be needed in patients with high CAC scores or scores with an increasing tendency when online-HDF is replaced with HDx with an MCO membrane.

Evaluation and comparison of polysulfone TS-UL and PMMA NF-U dialyzers versus expanded hemodialysis and postdilution hemodiafiltration.

Toray has created a new generation of dialyzers, the polysulphone (TS) UL series, and polymethylmethacrylate (PMMA) NF-U series, which offer enhanced efficacy over the previous TS-S series and NF-H series. The aim of this study was to evaluate the safety and efficacy of these dialyzer series versus contrasted expanded hemodialysis (HDx) and postdilution hemodiafiltration (HDF). We conducted a prospective study in 12 patients. Each patient underwent six dialysis sessions: FX80 Cordiax in HD, Toraysulfone TS-1.8 UL in HD, Theranova 400 in HDx, polymethylmethacrylate (PMMA) NF-2.1 U in HDF, Toraysulfone TS-2.1 UL in HDF, and FX80 Cordiax in HDF. The removal ratios (RRs) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. Dialysate albumin loss was also measured. The RRs for ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, and α1 -acid glycoprotein were higher with the TS-2.1 UL and FX80 Cordiax dialyzers in HDF than those obtained with HD treatments and NF-2.1 U in HDF. The ß2 -microglobulin, myoglobin, and prolactin RRs were also higher with HDx than those obtained with HD treatments. The myoglobin and prolactin RRs were higher with TS-1.8 UL in HD than those obtained with helixone dialyzers in HD. Dialysate albumin loss was less than 3 g in all situations except in TS-2.1 UL in HDF. The highest global removal score values were obtained with the TS-2.1 UL and helixone dialyzers in HDF. Significant differences were found between all study situations. In conclusion, the new generation dialyzers, Toraysulfone TS Series UL and PMMA NF-U series, show excellent behaviour and tolerance in HD and HDF, representing an upgrade versus their predecessor series. The higher permeability of the TS UL series has been proven with higher efficiency in HD and maximum performance in HDF. The new PMMA NF-U series allows the use of HDF with good efficiency and complete safety.

Artificial liver support systems.

Artificial liver systems are used to bridge between transplantation or to allow a patient's liver to recover. They are used in patients with acute liver failure (ALF) and acute-on-chronic liver failure. There are five artificial systems currently in use: molecular adsorbent recirculating system (MARS), single-pass albumin dialysis (SPAD), Prometheus, selective plasma filtration therapy, and hemodiafiltration. The aim is to compare existing data on the efficiency of these devices. A literature search was conducted using online libraries. Inclusion criteria included randomized control trials or comparative human studies published after the year 2000. A systematic review was conducted for the five individual devices with a more detailed comparison of the biochemistry for the SPAD and MARS systems. Eighty-nine patients were involved in the review comparing SPAD and MARS. Results showed that there was an average reduction in bilirubin (-53 µmol/L in MARS and -50 µmol/L in SPAD), creatinine (-19.5 µmol/L in MARS and -7.5 µmol/L in SPAD), urea (-0.9 mmol/L in MARS and -0.75 mmol/L in SPAD), and gamma-glutamyl transferase (-0.215 µmol/L·s in MARS and -0.295 µmol/L·s in SPAD) in both SPAD and MARS. However, there was no significant difference between the changes in the two systems. This review demonstrated that both MARS and SPAD aid recovery of ALF. There is no difference between the efficiency of MARS and SPAD. Because of the limited data, there is a need for more randomized control trials. Evaluating cost and patient preference would aid in differentiating the systems.

Practice Patterns and Outcomes of Online Hemodiafiltration: A Real-World Evidence Study in a Russian Dialysis Network.

BACKGROUND: Evidence suggests that online hemodiafiltration (OL-HDF) is associated with improved survival. Whether the dose-response relationship between convective volume and mortality may be confounded by selection bias or descends from practice patterns is not clear. We sought to evaluate the role of patients' characteristics and practice patterns on OL-HDF dose and mortality in a large private dialysis network in the Republic of Russia. METHODS: In this multicenter, historical cohort study, we included adult incident patients on OL-HDF with at least 90 days of survival on renal replacement therapy in centers belonging to the Russian Federation Fresenius Medical Care network (January 1, 2011, to December 31, 2016). We evaluated predictors and outcomes (survival) of substitution volume target achievement (Qsub > 21 L/session). RESULTS: Among 1,081 enrolled patients, the average Qsub was 22.9 (±3.2) L/session; the mean ultrafiltration volume was 1.6 (±0.8) L/session. The mean age was 55.8 ± 13.2; 42% were woman. Most common comorbidities were congestive heart failure (39.7%) and peripheral vascular disease (21.7%). The average hemoglobin was 9.3 ± 1.3. The case-mix adjusted center effect accounted for 20% of variance in Qsub. The top 10 most important variables associated with higher Qsub were effective Qb, serum protein, Charlson's comorbidity index, hemoglobin, year of dialysis initiation (proxy of high Qsub treatment policy in the clinic network), predialysis heart rate, serum bicarbonate, serum phosphate, age, serum sodium, and dry body weight. In addition, we found that the association of Qb with Qsub is moderated by year of enrollment, intradialytic weight gain, and coronary artery disease, whereas higher hemoglobin concentration moderated the relationship between treatment time and Qsub. Finally, Qsub between 21 and 25 L/session was associated with longer 5-year survival. CONCLUSIONS: Both center-dependent clinical practice standards and patient clinical conditions substantially contributed to the risk of low Qsub. We confirmed previous evidence indicating better survival among patients with Qsub ≥ 21 L/session.

Modeling the transfer of low molecular weight plasma proteins during hemodialysis and online hemodiafiltration.

Replacing the renal excretion of low molecular weight proteins (LMWP) by extracorporeal dialysis (dialysis) treatment poses technological challenges. Hemodialyzers with sieving coefficients for LMWP that match or even exceed those of the glomerular membrane barrier are commercially available; however, the associated losses of albumin are much higher than physiological levels of renal albumin excretion. A unidimensional, convection-diffusion model of solute transfer has been developed to analyze and quantitate LMWP extraction and albumin loss during dialysis treatment. The model is applicable to any extracorporeal dialysis technique and any type of hemodialyzer. Clinical extraction data for beta 2 microglobin (ß2M, 11.6 kDa), myoglobin (16.7 kDa) and interleukin 6 (IL6, 21-30 kDa) from 15 patients on hemodiafiltration (HDF) using a Nipro Elisio H series high flux hemodialyzer were analyzed using the model and values for the convection and mass transfer coefficients were derived. The model predicts that under normal clinical operating conditions, given equal amounts of ß2M removal, albumin losses are higher using pre-dilution rather than post-dilution HDF. The model can be used to provide estimates of the internal filtration rates of hemodialyzers operating in vivo.

Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study.

BACKGROUND: Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. AIM: Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. METHODS: An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. RESULTS: The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. CONCLUSIONS: EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.

Public health benefits of water purification using recycled hemodialyzers in developing countries.

In rural regions with limited resources, the provision of clean water remains challenging. The resulting high incidence of diarrhea can lead to acute kidney injury and death, particularly in the young and the old. Membrane filtration using recycled hemodialyzers allows water purification. This study quantifies the public health effects. Between 02/2018 and 12/2018, 4 villages in rural Ghana were provided with a high-volume membrane filtration device (NuFiltration). Household surveys were collected monthly with approval from Ghana Health Services. Incidence rates of diarrhea for 5-month periods before and after implementation of the device were collected and compared to corresponding rates in 4 neighboring villages not yet equipped. Data of 1,130 villagers over 10 months from the studied communities were studied. Incidence rates showed a decline following the implementation of the device from 0.18 to 0.05 cases per person-month (ppm) compared to the control villages (0.11 to 0.08 ppm). The rate ratio of 0.27 for the study villages is revised to 0.38 when considering the non-significant rate reduction in the control villages. Provision of a repurposed hemodialyzer membrane filtration device markedly improves health outcomes as measured by diarrhea incidence within rural communities.

Early use of endotoxin absorption by oXiris in abdominal septic shock: A case report.

RATIONALE: Septic shock leads to multiple organ failure and increases mortality rate. We reported a critical patient with abdominal septic shock, which was the first case successfully treated with continuous renal replacement therapy (CRRT) and a newly designed endotoxin removal device oXiris in mainland China. PATIENT CONCERNS: A 51-year-old man developed gastric ulcer perforation after resection of a benign peritoneal tumor and had a second abdominal surgery. His blood pressure decreased to 70/40 mm Hg with oliguria, requiring large doses of noradrenaline and intravenous fluid for resuscitation. The abdominal cavity was not sutured after the second open surgery due to severe abdominal infection and distention. His leukocyte count was over 30109/L, while the blood lactic acid was 12.5 mmol/L and procalcitonin (PCT) was >100 ng/mL. DIAGNOSIS: Since the bacterial culture of peritoneal exudate showed positive with Enterobacter aerogenes and Pseudomonas aeruginosa after the second surgery, and the patient had severe low blood pressure, hyoxemia and oliguria, combined with the laboratory tests results, he was diagnosed with Gram-negative related septic shock, acute kidney injury, and multiple organ dysfunction. INTERVENTIONS: CRRT with oXiris membrane was performed for 80hours and followed by AN69 ST membranes during the subsequent 27 days. Antibiotics together with other medical treatment were applied to the patient in the meantime. OUTCOMES: At the end of 80 hours treatment with oXiris, PCT of the patient had decreased to 14.52 ng/mL and lactic acid decreased to 4.2 mmol/L. The total sequential organ failure assessment (SOFA) score decreased from 15 to 11. Urine output steadily increased to 250 mL/h, and vital signs and blood pressure were stable without noradrenaline. At the end of the 27 days of conventional CRRT, his kidney function had completely recovered with a total sequential organ failure assessment score (SOFA score) of 6. LESSONS: oXiris, with its enhanced endotoxin adsorption, appeared to accelerate improvement in organ dysfunction and ultimate survival in our patient. In critical patients with abdominal septic shock, oXiris is an important adjunctive consideration to supplement definitive source control and antimicrobial therapy.

Evaluation of low-volume post-dilution online hemodiafiltration with Japanese high-performance hemodiafilters.

PURPOSE: To assess the removal performance of low-volume post-hemodiafiltration (HDF) with Japanese hemodiafilters and the removal performance with 20 % reduction in the total dialysate flow rate (Qdtotal). METHODS: Subjects were 8 patients undergoing pre-HDF. Study 1: Post-HDF was performed at a blood flow rate (Qb) of 250 mL/min and a total volume of substitution fluid (Vs) of 12 L/session(s) for 4 hrs using Fineflux-210Seco (FIX), ABH-21PA (ABH), and NVF-21H (NVF). We assessed removal efficiency of small molecular solutes, low-molecular-weight-proteins and the amount of albumin loss. Study 2: Post-HDF was performed at Vs of 12 L/s under G-1, Qdtotal of 500 and Qb of 250 mL/min; G-2, Qdtotal of 400 and Qb of 250 mL/min; and G-3, Qdtotal of 400 and Qb of 300 mL/min. Removal efficiency was compared and analyzed between these conditions. RESULTS: Study 1: The results using FIX, ABH and NVF are shown in order. The Kt/V were 1.8, 1.9 and 1.8. The ß2-Microglobulin (MG) removal rate (RR) (%) were 81.2, 83.1 and 82.8, and the α1-MG RR were 37.4, 40.2 and 38.5, respectively. Study 2: The results in G-1, 2 and 3 are shown in order. The Kt/V and the RR of small solutes, were significantly higher in G-3. The ß2-MG RR (%) were 81.2, 80.1 and 81.0, and the α1-MG RR were 37.4, 37.5 and 38.0, respectively. CONCLUSIONS: Low-volume post-HDF performed at Qb of 250 mL/min with Japanese high-performance hemodiafilters exhibited favorable removal efficiency for all solutes. Even with 20 % reduction in Qdtotal, the removal performance was also favorable.

Enhancement of solute clearance using pulsatile push-pull dialysate flow for the Quanta SC+: A novel clinic-to-home haemodialysis system.

BACKGROUND AND OBJECTIVE: The SC+ haemodialysis system developed by Quanta Dialysis Technologies is a small, easy-to-use dialysis system designed to improve patient access to self-care and home haemodialysis. A prototype variant of the standard SC+ device with a modified fluidic management system generating a pulsatile push-pull dialysate flow through the dialyser during use has been developed for evaluation. It was hypothesized that, as a consequence of the pulsatile push-pull flow through the dialyser, the boundary layers at the membrane surface would be disrupted, thereby enhancing solute transport across the membrane, modifying protein fouling and maintaining the surface area available for mass and fluid transport throughout the whole treatment, leading to solute transport (clearance) enhancement compared to normal haemodialysis (HD) operation. METHODS: The pumping action of the SC+ system was modified by altering the sequence and timings of the valves and pumps associated with the flow balancing chambers that push and pull dialysis fluid to and from the dialyser. Using this unique prototype device, solute clearance performance was assessed across a range of molecular weights in two related series of laboratory bench studies. The first measured dialysis fluid moving across the dialyser membrane using ultrasonic flowmeters to establish the validity of the approach; solute clearance was subsequently measured using fluorescently tagged dextran molecules as surrogates for uraemic toxins. The second study used human blood doped with uraemic toxins collected from the spent dialysate of dialysis patients to quantify solute transport. In both, the performance of the SC+ prototype was assessed alongside reference devices operating in HD and pre-dilution haemodiafiltration (HDF) modes. RESULTS: Initial testing with fluorescein-tagged dextran molecules (0.3 kDa, 4 kDa, 10 kDa and 20 kDa) established the validity of the experimental pulsatile push-pull operation in the SC+ system to enhance clearance and demonstrated a 10 to 15% improvement above the current HD mode used in clinic today. The magnitude of the observed enhancement compared favourably with that achieved using pre-dilution HDF with a substitution fluid flow rate of 60 mL/min (equivalent to a substitution volume of 14.4 L in a 4-hour session) with the same dialyser and marker molecules. Additional testing using human blood indicated a comparable performance to pre-dilution HDF; however, in contrast with HDF, which demonstrated a gradual decrease in solute removal, the clearance values using the pulsatile push-pull method on the SC+ system were maintained over the entire duration of treatment. Overall albumin losses were not different. CONCLUSIONS: Results obtained using an experimental pulsatile push-pull dialysis flow configuration with an aqueous blood analogue and human blood ex vivo demonstrate an enhancement of solute transport across the dialyser membrane. The level of enhancement makes this approach comparable with that achieved using pre-dilution HDF with a substitution fluid flow rate of 60 mL/min (equivalent to a substitution volume of 14.4 L in a 4-hour session). The observed enhancement of solute transport is attributed to the disruption of the boundary layers at the fluid-membrane interface which, when used with blood, minimizes protein fouling and maintains the surface area.

Comparison of the removal of uraemic toxins with medium cut-off and high-flux dialysers: a randomized clinical trial.

BACKGROUND: Accumulation of middle-weight uraemic toxins in haemodialysis (HD) patients results in increased morbidity and mortality. Whether medium cut-off HD (MCO-HD) improves removal of middle-weight uraemic toxins remains to be demonstrated. METHODS: This cross-over prospective study included 40 patients randomly assigned to receive either 3 months of MCO-HD followed by 3 months of high-flux HD (HF-HD), or vice versa. The primary endpoint was myoglobin reduction ratio (RR) after 3 months of MCO-HD. Secondary endpoints were the effect of MCO-HD on other middle-weight toxins and protein-bound toxins, and on parameters of nutrition, inflammation, anaemia and oxidative stress. RESULTS: Compared with HF-HD, MCO-HD provided higher mean RR of myoglobin (36 ± 8 versus 57 ± 13%, P < 0.0001), beta2-microglobulin (68 ± 6 versus 73 ± 15%, P = 0.04), prolactin (32 ± 13 versus 59 ± 11%, P < 0.0001), fibroblast growth factor 23 (20 ± 21 versus 41 ± 22%, P = 0.0002), homocysteine (43 ± 7 versus 46 ± 9%, P = 0.03) and higher median RR of kappa [54 (48-58) versus 70 (63-74)%, P < 0.0001] and lambda free light chain (FLC) [15 (9-22) versus 44 (38-49)%, P < 0.0001]. Mean ± SD pre-dialysis levels of beta2-microglobulin (28.4 ± 5.6 versus 26.9 ± 5.1 mg/L, P = 0.01) and oxidized low-density lipoprote (6.9 ± 4.4 versus 5.5 ± 2.5 pg/mL, P = 0.04), and median (interquartile range) kappa FLC [145 (104-203) versus 129 (109-190) mg/L, P < 0.03] and lambda FLC [106 (77-132) versus 89 (62-125) mg/L, P = 0.002] were significantly lower. Mean albumin levels decreased significantly (38.2 ± 4.1 versus 36.9 ± 4.3 g/L, P = 0.004), without an effect on nutritional status as suggested by unchanged normalized protein catabolic rate and transthyretin level. CONCLUSIONS: Compared with HF-HD, MCO-HD provides higher myoglobin and other middle molecules RR and is associated with moderate hypoalbuminemia. The potential benefits of this strategy on long-term clinical outcomes deserve further evaluation.

Study of Biocompatibility of Membranes in Online Hemodiafiltration.

BACKGROUND: The biocompatibility of dialysis membranes is a determining factor in avoiding chronic microinflammation in patients under haemodialysis. Lower biocompatibility has been related to increased inflammatory status, which is known to be associated with cardiovascular events. Classically, cellulose membranes have been considered bioincompatible. A new-generation of asymmetric cellulose triacetate (CTA) membranes allows the performance of high convective transport techniques, but there have been no studies of their biocompatibility. The aim of the present study was to analyze and compare the biocompatibility characteristics of 4 membranes, including CTA, in online hemodiafiltration (OL-HDF) patients. METHODS: We included 15 patients in -OL-HDF. After a 2-week washout period with helixone membrane, each patient was treated with the 4 membranes (polyamide, polynephron, helixone and CTA) for 4 weeks in a randomized order. The other dialysis parameters were kept stable throughout the study. We studied changes in markers of the activation of the complement system, monocytes, platelets, and adhesion molecules with the 4 membranes, as well as inflammatory parameters. RESULTS: Biocompatibility was similar among the membranes. There were no sustained differences in complement activation, measured by C3a and C5a levels, or in platelet activation, determined by levels of P-selectin and platelet-derived microparticles (CD41a+). No differences were observed in activated monocyte levels (CD14+/CD16+) or in plasma levels of interleukin (IL)-1, IL-6, IL-10 or high-sensitivity C-reactive protein, although tumour necrosis factor-α levels decreased when the patients were dialyzed with CTA. No significant differences were found in markers of endothelial damage, assessed by levels of plasminogen activator inhibitor-1 and adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1). CONCLUSION: The 4 membranes evaluated in this study in stable patients on OL-HDF, including the new-generation CTA, show similar biocompatibility with the methods applied.

Valoración de la influencia de la superficie de la membrana y el flujo sanguíneo en dializadores de medio cut-off / Evaluation of the influence of the surface membrane and blood flow in medium «cut-off» (MCO) dialyzers

INTRODUCCIÓN: Recientemente, se ha incorporado a nuestras posibilidades terapéuticas una nueva clase de dializadores, las membranas de medio cut-off (MCO), diseñadas para mejorar la permeabilidad y que podrían alcanzar una eficacia similar a la hemodiafiltración. Para aumentar el conocimiento sobre su uso, el objetivo del estudio fue valorar en las membranas de MCO el efecto de la superficie y del flujo sanguíneo (Qb) sobre la eficacia depurativa. MATERIAL Y MÉTODOS: Se incluyó a 19 pacientes en programa de hemodiálisis. Cada paciente recibió 6 sesiones, en las que se varió la superficie de membrana, de 1,7 o 2,0 m2, y el Qb (300, 350, 400 o 450 mL/min). En cada sesión se determinaron diferentes solutos al inicio y al final de la diálisis. RESULTADOS: El cambio de superficie del dializador no mostró diferencias significativas en la depuración de pequeñas o grandes moléculas, sin cambios en la pérdida de albúmina. El aumento del Qb se acompañó de un aumento de depuración de pequeñas moléculas, sin mostrar diferencias en el porcentaje de reducción de β2-microglobulina, mioglobina, prolactina, α1-microglobulina y α1-glicoproteína ácida, a excepción de alguna comparación con Qb 450mL/min. Tampoco se observaron diferencias en la pérdida de albúmina en el líquido de diálisis, inferior a 2,5 g en todas las situaciones. CONCLUSIÓN: El incremento de la superficie de 1,7 a 2,0 m2 en el dializador de MCO no ha significado una mayor eficacia depurativa. En estos dializadores el aumento del Qb no parece ser tan determinante como en la hemodiafiltración, a excepción de la depuración de pequeñas moléculas

INTRODUCTION: Recently, a new class of dialyzers, medium cut-off membranes (MCO), designed to improve the permeability, which could provide an efficacy similar to hemodiafiltration, have been incorporated into our therapeutic possibilities. To increase the knowledge about its use, the objective of the study was to evaluate the effect of the surface and blood flow (Qb) on the depurative efficacy in the MCO membranes. MATERIAL AND METHODS: We included 19 patients in the hemodialysis. Each patient received 6 sessions, in which the membrane surface was varied, from 1.7 to 2.0 m2, and/or the Qb (300, 350, 400 or 450 mL/min). In each session, different solutes were determined at the beginning and end of dialysis. RESULTS: The surface change of the dialyzer did not show significant differences in the removal of small or large molecules, without changes in albumin loss. The increase in Qb was accompanied by an increase in clearance of small molecules, without showing differences in the percentage reduction of β2-microglobulin, myoglobin, prolactin, α1-microglobulin and α1-acid glycoprotein, except for some comparison with Qb 450 mL/min. There were also no differences in the loss of albumin in the dialysis fluid, less than 2.5 g in all situations. CONCLUSION: The increase of the surface area from 1.7 to 2.0 m2 in the MCO dialyzer has not meant a greater depurative effectiveness. In these dialyzers the increase of Qb does not seem to be as determinant as in hemodiafiltration except for the clearance of small molecules

The Effect of Dialysis Modality and Membrane Performance on Native Immunity in Dialysis Patients.

Chronic Kidney Disease (CKD) is characterized by immune activation with development of chronic inflammation. However, immune deficiency also exists in CKD patients. The number and the activity of Natural Killer cells (NK-cells) are influenced by the biocompatibility of various dialysis membranes. In this study we investigated the effect of dialysis modality and membrane type on NK-cell number and on phagocytic activity of neutrophils in patients on different dialysis methods. Sixty patients were included in the study and divided in three groups of 20 patients each. Patients on conventional hemodialysis using Low Flux membrane (cHD-LF) were included in Group I, patients on conventional dialysis using High Flux membrane (cHD-HF) were included in Group II and patients treated by on-line hemodiafiltration with High Flux polysulphone membrane (on-line HDF) were included in Group III. Native immunity was investigated using the number of NK-cells and the phagocytic activity of neutrophils. NK-cells count was significantly lower (p<0.001) in the three groups of dialyzed patients in comparison to healthy subjects. However, no significant difference was observed in the NK-cells count among patients treated by conventional dialysis using Low or High Flux membrane and patients treated by on-line hemodiafiltration. Similarly, although the phagocytic activity of neutrophils was significantly decreased in all patients on dialysis (p<0.001), no difference related to the dialysis modality or membrane performance was observed. A strong positive correlation was recognized between parathormone blood levels and number of NK-cells (r=0.305, p<0.01). In conclusion, an impairment of the native immunity represented by NK cell number and phagocytic activity of neutrophils is observed in patients on dialysis. Dialysis modality and membrane performance do not influence the native immunity of dialyzed patients. However, parathormone blood levels are possibly involved in the development of immune system disturbances in such patients.

Albumin losses during hemodiafiltration: all dialyzers are not created equal - a case report.

BACKGROUND: Online hemodiafiltration (OL-HDF) is associated with better removal of both small and middle molecules and might improve survival compared to conventional hemodialysis (HD). Nevertheless, hemodiafiltration (HDF) can lead to an increase in albumin loss across the dialyzer, especially with high permeability membrane and high convective volume (CV). We present the case of a patient treated by OL-HDF who developed severe hypoalbuminemia resulting from massive albumin loss into dialysate. CASE PRESENTATION: A 71-year-old woman with ESRD started renal replacement therapy in December 2016. She was treated by high volume post-dilution OL-HDF, 4 h, 3 times per week. The dialyzer was the Phylther HF20SD (a 2.0m2 heat sterilized high flux (HF) polyphenylene membrane from Bellco). At the initiation of dialysis, the serum albumin was 4.0 g/dl. During the following months, the patient developed severe hypoalbuminemia. The lowest value observed was 2.26 g/dl in July 2017. Diagnostic workup excluded nephrotic syndrome, hepatic failure and malabsorption. The patient was shifted from OL-HDF to standard HF HD, keeping the same dialyzer and dialysis schedule. During the following months, we observed a progressive correction of the hypoalbuminemia (3.82 g/dl at last follow-up). To precise the impact of the epuration technique on the albumin losses in this patient, we measured the amount of albumin in dialysate during one session with the Phylther HF20SD on OL-HDF and one session with the same filter but on standard HD. The CV was 29.0 l for the HDF session. The total albumin losses were 23.6 g on OL-HDF and 4.6 g on HD. CONCLUSION: OL-HDF can lead to significant albumin loss into the dialysate, especially with high permeability membrane and high CV. When prescribing post-dilutional OL-HDF, the choice of the dialyzer membrane should be made with caution. Users of the steam sterilized polyphenylene membrane, the Phylther SD, should be informed of the risk of large albumin loss with this membrane during post-dilution OL-HDF.

Evaluation of Proteins and Cells that Adsorb to Dialysis Membranes Used in Continuous Hemodiafiltration: Comparison of AN69ST, Polymethylmethacrylate, and Polysulfone Membranes.

OBJECTIVE: In intensive care medicine, continuous renal replacement therapy (CRRT) is important for critically ill patients. Various types of dialysis membranes are currently used in clinical settings, each having unique structures and characteristics. This study aimed to perform a detailed analysis of the characteristics of polysulfone (PS), polymethylmethacrylate (PMMA), and polyacrylonitrile (AN69ST) membranes, and to determine differences in the adsorption of proteins and blood cells by membrane material. METHODS: Subjects were patients undergoing CRRT in the ICU of the Kokura Memorial Hospital. After use, membranes were collected and analyzed. Semi-quantitative analysis of the membrane surface was performed by scanning electron microscopy. We determined the identity of proteins adsorbed to the surface of membranes by TOF/MS analysis, and measured the amount of adsorbed chemical mediators. RESULTS: Electron microscopy revealed that, compared to PS and PMMA membranes, AN69ST membranes had a greater amount of adsorbed activated white blood cells (WBCs). A large amount of platelets was adsorbed to PMMA membranes. In terms of the amount of adsorbed protein, significantly more proteins adsorbed to AN69ST membranes compared to PS and PMMA membranes. Moreover, TOF/MS analysis revealed a difference in the types of adsorbed proteins by membrane. Chemokines were particularly prevalent among adsorbed proteins for all 3 membranes. CONCLUSION: Compared to PS and PMMA membranes, AN69ST membranes had a higher capacity to remove activated WBCs. Moreover, apparent differences were noted in the types of proteins that adsorbed to each type of membrane. These differences in membrane properties may impact clinical outcomes.

A Clinical Significance of Intermittent Infusion Hemodiafiltration Using Backfiltration of Ultrapure Dialysis Fluid Compared to Hemodialysis: A Multicenter Randomized Controlled Crossover Trial.

BACKGROUND: Intermittent infusion hemodiafiltration -(I-HDF) using repeated infusion of ultrapure dialysis fluid through a dialysis membrane or sterile nonpyrogenic substitution fluid was developed to prevent a rapid decrease in blood pressure by increasing the patient's circulating blood volume, to enhance the plasma refilling rate by improving peripheral circulation, and to enhance solute transfer from the extravascular space to the intravascular space by enhancing the plasma refilling rate. Furthermore, the effect of fouling caused by attachment of proteins to the membrane as a result of ultrafiltration can be reduced by backflushing of the membrane with the purified dialysate in I-HDF. Although there have been several clinical trials of I-HDF, there have been no comparisons of the clinical significance of and indications for -I-HDF with those of conventional hemodialysis (HD). OBJECTIVE: The aim of this multicenter randomized controlled crossover trial was to compare the clinical significance of -I-HDF with that of HD in Japan. METHOD: Patients were randomized to receive HD, I-HDF, and HD (group A) or I-HDF, HD, and I-HDF (group B) in that order for 14 weeks each. The sample size of 70 was determined based on the operability and patient availability. Treatment outcomes were evaluated 5 and 14 weeks after the start of each treatment period. The patients received 4-h treatment sessions with no changes in session duration or anticoagulant therapy during the study. I-HDF was performed using a GC-110N dialysis machine. Two hundred milliliters of ultrapure dialysis fluid were infused at a rate of 150 mL/min by backfiltration every 30 min during treatment. The first and last infusions were performed 30 min after the start and 30 min before the end of treatment, respectively. The total estimated infusion volume per session was 1.4 L (i.e., 200 mL × 7 infusions). I-HDF is a type of online HDF with a small fluid replacement volume. An ABH-P polysulfone membrane hemodiafilter was used for -I-HDF and a class 1 or 2 hemodialyzer with a polysulfone membrane not coated with vitamin E and approved by the Japanese reimbursement system was used for HD. The primary outcomes were the Short Form-36 version 2 summary scores for quality of life and the visual analog scale scores for clinical symptoms. Secondary outcomes were vital signs, number of interventions, and pre-treatment blood test results. These variables were evaluated 1 week before at the start of the study, and at 5 and 14 weeks after the start of each treatment period. The removal characteristics of the various solutes were evaluated when possible on the first day of each treatment period. All patients provided written informed consent to participate. RESULTS: Thirty-two patients in group A and 32 patients in group B completed the trial. There were no differences in the primary or secondary outcomes between I-HDF and HD. Serum α1-microglobulin (MG) levels at 14 weeks were significantly lower for I-HDF than for HD. During treatment, the removal rates for urea and creatinine, which are low molecular weight substances, were significantly lower during I-HDF than during HD. In contrast, the ß2-MG and α1-MG removal rates were significantly higher during I-HDF than during HD. Furthermore, there was significantly less albumin leak during I-HDF than during HD. The solute removal results reflect the difference in pore size between the hemodiafilter used for I-HDF and the hemodialyzer used for HD and the difference in convective transport attributable to filtration between the 2 methods. CONCLUSIONS: These findings show that the removal rates of low molecular weight substances are significantly lower and those of medium to high molecular weight substances are significantly higher with I-HDF than with HD. They also indicate that there is significantly less albumin leak during I-HDF than during HD, meaning that I-HDF may be a particularly suitable dialysis modality for patients with malnutrition and the elderly in Japan.

Transcapillary Refilling Rate and Its Determinants during Haemodialysis with Standard and High Ultrafiltration Rates.

BACKGROUND: Achieving euvolaemia using ultrafiltration (UF) during haemodialysis (HD) without inducing haemodynamic instability presents a major clinical challenge. Transcapillary refill is a key factor in sustaining the circulating blood volume (BV) during UF, which is in turn predicted by the rate of refilling. However, absolute plasma refilling rate (PRR), its determinants and variability with UF rate (UFR), have not been reported in the literature. METHOD: We studied paired HD sessions (n = 48) in 24 patients over 2 consecutive mid-week HD treatments. Plasma refilling was measured using real-time, minute-by-minute relative BV changes obtained from the integrated BV monitoring device during UF. A fixed bolus dilution approach at the start of HD was used to calculate absolute BV. The first control HD session was undertaken with a standard UFR required to achieve the prescribed target weight, while during the second study session, a fixed (high) UFR (1 L/h) was applied, either in the first (n = 12 patients) or in the final hour (n = 12 patients) of the HD session. Participants' had their hydration status measured pre- and post-HD using multifrequency bioimpedance (BIS). Blood pressure was measured at 15-min intervals and blood samples were collected at 7 intervals during HD sessions. RESULTS: The mean PRR during a standard 4-hr HD session was 4.3 ± 2.0 mL/kg/h and varied between 2 and 6 mL/kg/h. There was a mean time delay of 22 min (range 13.3-35.0 min) for onset of plasma refilling after the application of UF irrespective of standard or high UFRs. The maximum refilling occurred during the second hour of HD (mean max PRR 6.8 mL/kg/h). UFR (beta = 0.60, p < 0.01) and BIS derived pre-HD overhydration index (beta = 0.44, p = 0.01) were consistent, independent predictors of the mean PRR (R2 = 0.49) in all HD sessions. At high UFRs, PRR exceeded 10 mL/kg/h. The total overall plasma refill contribution to UF volume was not significantly different between standard and high UF. During interventions no significant haemodynamic instability was observed in the study. CONCLUSION: We describe absolute transcapillary refilling rate and its profile during HD with UF. The findings provide the basis for the development of UF strategies to match varying PRRs during HD. An approach to fluid removal, which is tailored to patients' refilling rates and capacity, provides an opportunity for more precision in the practice of UF.