Most recently developed polyester polymer alloy dialyzer: A new medium cut-off membrane?

BACKGROUND: New versions of the polyester polymer alloy (PEPA) membrane have appeared over the years, with increases in both the pore size and the amount of polyvinylpyrrolidone (PVP) to optimize hydrophilicity performance. This study aimed to assess the efficacy of the most recently developed PEPA dialyzer, the FDY series, in hemodialysis (HD) modality in terms of uremic toxin removal and albumin loss and to compare it with that of several high-flux dialyzers currently used in HD and post-dilution hemodiafiltration (HDF) treatments. METHODS: A prospective study was carried out in 21 patients. All patients underwent six dialysis sessions with the same routine dialysis parameters; only the dialyzer and/or the dialysis modality varied: FX80 in HD, FDY 180 in HD, Clearum HS17 in HDF, Elisio 19H in HDF, Vitapes 180 in HDF, and FX80 in post-dilution HDF. The reduction ratios (RR) of urea, creatinine, ß2-microglobulin, myoglobin, κFLC, prolactin, α1-microglobulin, α1-acid glycoprotein, λFLC, and albumin were compared intraindividually. Dialysate albumin loss was also measured. RESULTS: Both membranes FDY and FX80 are high-flux dialyzers and are applied here in high-flux HD. The average RR of ß2-microglobulin was slightly lower in the two HD treatments than in the HDF treatments. Comparison of dialysis treatments revealed that the PEPA FDY dialyzer in the HD modality was more effective than the FX80 dialyzer in high-flux HD and was as effective as post-dilution HDF, especially in terms of myoglobin, κFLC, prolactin, α1-microglobulin, and λFLC RRs. The FDY treatments obtained similar albumin RR in blood and slightly higher dialysate albumin loss, although the values were clinically acceptable. CONCLUSIONS: The most recently developed PEPA dialyzers in the HD modality were as effective as all treatments in the HDF modality and were clearly superior to high-flux helixone HD treatment. These results confirm that this dialyzer should be categorized within the medium cut-off (MCO) membrane classification.

Extracorporeal Techniques in Kidney Failure.

During the last decades, various strategies have been optimized to enhance clearance of a variable spectrum of retained molecules to ensure hemodynamic tolerance to fluid removal and improve long-term survival in patients affected by kidney failure. Treatment effects are the result of the interaction of individual patient characteristics with device characteristics and treatment prescription. Historically, the nephrology community aimed to provide adequate treatment, along with the best possible quality of life and outcomes. In this article, we analyzed blood purification techniques that have been developed with their different characteristics.

Results of Salt Intake Restriction Monitored with the New Sodium Control Biosensor.

INTRODUCTION: Adherence to a low-sodium (Na) diet is crucial in patients under hemodialysis, as it improves cardiovascular outcomes and reduces thirst and interdialytic weight gain. Recommended salt intake is lower than 5 g/day. The new 6008 CAREsystem monitors incorporate a Na module that offers the advantage of estimating patients' salt intake. The objective of this study was to evaluate the effect of dietary Na restriction for 1 week, monitored with the Na biosensor. METHODS: A prospective study was conducted in 48 patients who maintained their usual dialysis parameters and were dialyzed with a 6008 CAREsystem monitor with activation of the Na module. Total Na balance, pre-/post-dialysis weight, serum Na (sNa), changes in pre- to post-dialysis sNa (ΔsNa), diffusive balance, and systolic and diastolic blood pressure were compared twice, once after 1 week of patients' usual Na diet and again after another week with more restricted Na intake. RESULTS: Restricted Na intake increased the percentage of patients on a low-Na diet (<85 Na mmol/day) from 8% to 44%. Average daily Na intake decreased from 149 ± 54 to 95 ± 49 mmol, and interdialytic weight gain was reduced by 460 ± 484 g per session. More restricted Na intake also decreased pre-dialysis sNa and increased both intradialytic diffusive balance and ΔsNa. In hypertensive patients, reducing daily Na by more than 3 g Na/day lowered their systolic blood pressure. CONCLUSIONS: The new Na module allowed objective monitoring of Na intake, which in turn could permit more precise personalized dietary recommendations in patients under hemodialysis.

Long-term peridialytic blood pressure changes are related to mortality.

BACKGROUND: In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. METHODS: To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. RESULTS: During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality. CONCLUSION: Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.

Efficacy and Safety of the Medium Cut-Off Elisio HX Dialyzer.

INTRODUCTION: The medium cut-off Elisio HX dialyzer by Nipro became commercially available in Europe in 2021, but there are still no reports of in vivo data. This study aimed to evaluate the safety and efficacy of it compared with previously evaluated hemodialysis (HD), expanded HD (HDx), and postdilution hemodiafiltration (HDF) treatments. METHODS: A prospective study was carried out on 18 patients who underwent 5 dialysis sessions: FX80 Cordiax in HD, Elisio H19 in HD, Elisio HX19 in HDx, Theranova 400 in HDx, and FX80 Cordiax in HDF. The reduction ratios of urea, creatinine, ß2-microglobulin, myoglobin, kappa FLC, prolactin, α1-microglobulin, α1-acid glycoprotein, lambda FLC, and albumin were compared. Dialysate albumin loss was measured. RESULTS: The comparison between the different dialysis modalities revealed no difference for small molecules, but HDx and HDF were significantly more efficient than HD for medium and large molecule removal. The efficacy of Elisio HX19 dialyzer in HDx was similar to the Theranova 400, superior to both dialyzers in HD, and slightly lower than HDF. Albumin losses in dialysate with HD dialyzers were less than 1 g, but between 1.5 and 2.5 g in HDx and HDF. The global removal score (GRS) values with HDx treatments were statistically significantly higher than those with HD. The highest GRS was obtained with the helixone dialyzer in HDF. CONCLUSIONS: The new MCO dialyzer, Elisio HX, performs with excellent behavior and tolerance. It represents an upgrade compared to their predecessor and is very close to the removal capacity of HDF treatment.

Hemodiafiltration (HDF) versus expanded hemodialysis (HDx).

Medium cutoff (MCO) membranes have resulted in a novel dialyzer class designed to improve membrane permeability and have been postulated as an alternative to online hemodiafiltration since MCO membranes may achieve similar solute clearances. These membranes have been incorporated into clinical practice, and the term expanded HD (HDx) has been proposed to differentiate from high-flux hemodialysis. Efficacy, safety, and quality of life comparison of HDF versus HDx have been reviewed in this article.

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.

Humoral and Cellular Responses to mRNA-1273 and BNT162b2 SARS-CoV-2 Vaccines Administered to Hemodialysis Patients.

RATIONALE & OBJECTIVE: Patients with kidney failure who are receiving maintenance dialysis have a higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and worse clinical outcomes after coronavirus disease 2019 (COVID-19) than the general population. Therefore, immunization against SARS-CoV-2 with effective vaccines is an important component of health-maintenance strategies for these patients. This study evaluated the humoral and cellular responses to messenger RNA (mRNA) SARS-CoV-2 vaccines in this population. STUDY DESIGN: Observational prospective multicenter cohort study. SETTING & PARTICIPANTS: 205 patients treated at 3 dialysis units at the Hospital Clínic of Barcelona (Spain) were vaccinated from February 3 to April 4, 2021, and followed until April 23, 2021. EXPOSURE: Immunization with either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine. OUTCOME: Seroconversion, defined as the detection of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG), and the identification of activated CD4+T cells 3 weeks after completing vaccination. Anti-S1-RBD IgG levels were also analyzed as a secondary outcome. ANALYTICAL APPROACH: Univariate and multivariable logistic and multiple linear regression models were used to evaluate the associations between vaccination and study outcomes. RESULTS: We found that 97.7% of 175 vaccinated patients who were seronegative at baseline developed a response (humoral, cellular, or both); 95.4% of these patients seroconverted, while 62% of those tested for cellular immunity had a positive response. Greater age and immunosuppressive treatment were associated with lower antibody levels. LIMITATIONS: Mandatory vaccine administration by health authorities. Anti-S1-RBD IgG levels were reported up to 150U/mL and cellular immune responses were characterized qualitatively. Antibody assay and cellular response assessment may not be comparable with previously published laboratory approaches. CONCLUSIONS: Immunization with mRNA vaccines generated a humoral and cellular immune response in a high proportion of patients with kidney failure receiving maintenance dialysis. These findings as well as the high risk of infection and poor clinical outcomes among these patients make their vaccination a health priority.

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.

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.

SARS-CoV-2 Infection in a Spanish Cohort of CKD-5D Patients: Prevalence, Clinical Presentation, Outcomes, and De-Isolation Results.

INTRODUCTION: COVID-19 is a highly contagious disease that has easily spread worldwide. Outpatient maintenance hemodialysis seems to entail an increased risk of contagion, and previous reports inform of increased mortality among this population. METHODS: We retrospectively analyzed clinical and laboratory parameters, outcomes, and management once discharged of CKD-5D patients infected with SARS-CoV-2 from our health area. RESULTS: Out of the 429 CKD-5D population, 36 were diagnosed with SARS-CoV-2 infection (8%): 34 on in-center hemodialysis and 2 on peritoneal dialysis. Five were asymptomatic. The most common symptom was fever (70%), followed by dyspnea and cough. History of cardiovascular disease and elevation of LDH and C-reactive protein during admission were associated with higher mortality. Thirteen patients died (36%), 8 patients were admitted to an ICU, and survival was low (38%) among the latter. The mean time to death was 12 days. Most discharged patients got negative rRT-PCR in nasopharyngeal swabs within 26 days of diagnosis. However, there is a portion of cured patients that continue to have positive results even more than 2 months after the initial presentation. CONCLUSIONS: Patients on dialysis have an increased mortality risk if infected with SARS-CoV-2. Preventive measures have proven useful. Thus, proper ones, such as universal screening of the population and isolation when required, need to be generalized. Better de-isolation criteria are necessary to ensure an appropriate use of public health resources.

The probability of receiving a kidney transplantation in end-stage kidney disease patients who are treated with haemodiafiltration or haemodialysis: a pooled individual participant data from four randomised controlled trials.

BACKGROUND: Due to a critical shortage of available kidney grafts, most patients with Stage 5 Chronic Kidney Disease (CKD5) require bridging dialysis support. It remains unclear whether treatment by different dialysis modalities changes the selection and/or preparation of a potential transplant candidate. Therefore, we assessed whether the likelihood of receiving kidney transplant (both living or deceased kidney donors) differs between haemodialysis (HD) and online haemodiafiltration (HDF) in patients with CKD5D. METHODS: Individual participant data from four randomised controlled trials comparing online HDF with HD were used. Information on kidney transplant was obtained during follow-up. The likelihood of receiving a kidney transplant was compared between HD and HDF, and evaluated across different subgroups: age, sex, diabetes, history of cardiovascular disease, albumin, dialysis vintage, fistula, and level of convection volume standardized to body surface area. Hazard ratios (HRs), with corresponding 95% confidence intervals (95% CI), comparing the effect of online HDF versus HD on the likelihood of receiving a kidney transplant, were estimated using Cox proportional hazards models with a random effect for study. RESULTS: After a median follow-up of 2.5 years (Q1 to Q3: 1.9-3.0), 331 of the 1620 (20.4%) patients with CKD5D received a kidney transplant. This concerned 22% (n = 179) of patients who were treated with online HDF compared with 19% (n = 152) of patients who were treated with HD. No differences in the likelihood of undergoing a kidney transplant were found between the two dialysis modalities in both the crude analyse (HR: 1.07, 95% CI: 0.86-1.33) and adjusted analysis for age, sex, diabetes, cardiovascular history, albumin, and creatinine (HR: 1.15, 95%-CI: 0.92-1.44). There was no evidence for a differential effect across subgroups based on patient- and disease-characteristics nor in different categories of convection volumes. CONCLUSIONS: Treatment with HD and HDF does not affect the selection and/or preparation of CKD5D patients for kidney transplant given that the likelihood of receiving a kidney transplant does not differ between the dialysis modalities. These finding persisted across a variety of subgroups differing in patient and disease characteristics and is not affected by the level of convection volume delivered during HDF treatment sessions.

Percutaneous left atrial appendage closure, a safe alternative to anticoagulation for patients with nonvalvular atrial fibrillation and end-stage renal disease on hemodialysis: A single center experience.

The evidence about the effectiveness and safety of oral anticoagulation in patients on hemodialysis is conflicting and scarce. Percutaneous left atrial appendage occlusion (LAAO) has demonstrated to be a valid alternative therapeutic option for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study is to present the outcomes of percutaneous LAAO in patients with end-stage renal disease (ESRD) on hemodialysis and NVAF in our center. We conducted a retrospective review of clinical records, demographics, LAAO procedure, complications, and outcomes of patients with NVAF and ESRD on hemodialysis who underwent a percutaneous LAAO in our center between January 2017 and January 2019. In the period of the study, eight patients with ESRD on hemodialysis underwent a percutaneous LAAO in our center. The overall mean age was 67.5 years (range 56-81; SD ± 7.2). All patients had permanent NVAF. The total mean dialysis duration was 8.49 years (range 0.83-14.8; SD ± 6.2). The mean CHA2DS2-VASc and HAS-BLED scores were high (4.75 [SD ± 1.16] and 4.62 [SD ± 0.91], respectively). All patients had history of a major hemorrhagic event (BARC Score ≥3). Most patients (n = 6) showed left ventricular hypertrophy, and the average LVEF was 54% (SD ± 6.5). All devices were implanted successfully. Postprocedural antithrombotic regimen prescribed was based on antiplatelet therapy. No deaths, cardioembolic events, or major bleeding (according to the BARC scale) were reported during a mean follow-up of 14.24 months (SD ± 9.44). Percutaneous LAAO could be of particular interest in patients with NVAF and CKD in hemodialysis. Further studies will be necessary to confirm this hypothesis.

Determining factors for hemodiafiltration to equal or exceed the performance of expanded hemodialysis.

The aim of the study was to compare expanded hemodialysis (HDx) with hemodiafiltration (HDF) at different infusion flows to identify the main determinants, namely blood flow (Qb), replacement volume, infusion flow (Qi), ultrafiltration flow (Quf ), filtration fraction (FF), and the point at which the effectiveness of HDF equals or exceeds that of HDx. We conducted a prospective, single-center study in 12 patients. Each patient underwent 12 dialysis sessions: six sessions with Qb 350 and six with Qb 400 mL/min; with each Qb, one session was with HDx and five sessions were with FX80 (one in HD, and four with Qi 50, 75, 90/100 mL/min or autosubstitution in postdilution HDF). The reduction ratios (RR) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually and the global removal score (GRS) was calculated. The mean replacement volume with Qb 350 mL/min was 13.77 ± 0.92 L with Qi 50 mL/min, 20.75 ± 1.17 L with Qi 75, 23.83 ± 1.92 L with Qi 90, and 27.51 ± 2.77 L with autosubstitution. Similar results were obtained with Qb 400 mL/min, and the results were only slightly higher with Qi 100 mL/min or in autosubstitution. The GRS was positively correlated with replacement volume with Qb 350 (R2  = 0.583) and with Qb 400 (R2  = 0.584); with Quf with Qb 350 (R2  = 0.556) and with Qb 400 (R2  = 0.604); and also with FF with Qb 350 (R2  = 0.556) and with Qb 400 mL/min (R2  = 0.603). The minimum convective volume in HDF from which it is possible to overcome the efficacy of HDx was 19.2 L with Qb 350 and 17.6 L with Qb 400 mL/min. The cut-off point of Quf at which HDF exceeded the effectiveness of HDx was 80.6 mL/min with Qb 350 and 74.1 mL/min with Qb 400 mL/min. The cut-off point at which FF in HDF exceeded the effectiveness of the HDx was 23.0% with Qb 350 and 18.6% with Qb 400 mL/min. In conclusion, this study confirms the superiority of postdilution HDF over HDx when replacement volume, convective volume, Quf , or FF exceeds certain values. Increasing the Qb in postdilution HDF manages to increase the convective dose and more easily overcome the HDx.

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.

Vancomycin hemodialysis: Clearance differences between high-flux hemodialysis and on-line hemodiafiltration.

The aim of this study was to analyze the differences between vancomycin clearance (Kd) with high-flux hemodialysis (HFHD) and on-line hemodiafiltration (OL-HDF). The OL-HDF therapy combined the diffusion and convective transport of solutes. To compare the Kd, a vancomycin loading dose of 1 g was administered intravenously post-dialysis to 11 chronic and anuric (<100 mL/24 h) hemodialysis patients, undergoing HFHD and post-dilutional OL-HDF in consecutive therapies. Additional doses of 0.5 g were administered after 45 minutes at the end of each dialysis therapy during antibiotic treatment. Blood samples were drawn from arterial and venous lines at the start of hemodialysis sessions and at the first, second, third, and fourth hours. Additional samples were drawn at 15, 30, and 45 minutes after the end of dialysis therapy. Vancomycin plasma concentration, blood urea nitrogen (BUN), creatinine, and ß2 -microglobulin were measured. The patients' hydration status was evaluated by bioimpedance analysis. The mean of vancomycin dialyzer clearance (Kddc ) calculated was 110.8 ± 15 mL/min with HFHD and 146.8 ± 13.8 mL/min with OL-HDF (P = 0.025). Significant differences were also obtained for ß2 -microglobulin clearance, Kddc 72.6 ± 15.4 mL/min with HFHD and 113.4 ± 24.2 mL/min with OL-HDF (P = 0.012), whereas no differences were found for BUN or creatinine. Additionally, to analyze differences between HFHD and OL-HDF, a variable volume dual pool mathematical model was developed to estimate the body clearance (Kdbc ), extraction mass (Me ), and inter-compartment mass-transfer coefficient (K12 ) of each molecule. A higher vancomycin Kddc with OL-HDF produced by convection improved removal of antibiotic; this can compromise achieving a therapeutic concentration target. We recommended evaluating increased loading doses of vancomycin and avoiding administration during OL-HDF to assure adequate treatment.

High-permeability alternatives to current dialyzers performing both high-flux hemodialysis and postdilution online hemodiafiltration.

Most high-flux dialyzers can be used in both hemodialysis (HD) and online hemodiafiltration (OL-HDF). However, some of these dialyzers have higher permeability and should not be prescribed for OL-HDF to avoid high albumin losses. The aim of this study was to compare the safety and efficacy of a currently used dialyzer in HD and OL-HDF with those of several other high permeability dialyzers which should only be used in HD. A prospective, single-center study was carried out in 21 patients. Each patient underwent 5 dialysis sessions with routine dialysis parameters: 2 sessions with Helixone (HD and postdilution OL-HDF) and 1 session each with steam sterilized polyphenylene, polymethylmethacrylate (PMMA), and medium cut-off (MCO) dialyzers in HD treatment. The removal ratios (RR) of urea, creatinine, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, α1 -acid glycoprotein, and albumin were compared intraindividually. A proportional part of the dialysate was collected to quantify the loss of various solutes, including albumin. Urea and creatinine RRs with the Helixone-HDF and MCO dialyzers were higher than with the other 3 dialyzers in HD. The ß2 -microglobulin, myoglobin and prolactin RRs with Helixone-HDF treatment were significantly higher than those obtained with all 4 dialyzers in HD treatment. The ß2 -microglobulin value obtained with the MCO dialyzer was also higher than that obtained with the other 3 dialyzers in HD treatment. The myoglobin RR with MCO was higher than those obtained with Helixone and PMMA in HD treatment. The prolactin RR with Helixone-HD was significantly lower than those obtained in the other 4 study sessions. The α1 -microglobulin and α1 - acid glycoprotein RRs with Helixone-HDF were significantly higher than those obtained with Helixone and PMMA in HD treatment. The albumin loss varied from 0.54 g with Helixone-HD to 3.3 g with polyphenylene. The global removal score values ((UreaRR + ß2 -microglobulinRR + myoglobinRR + prolactinRR + α1 -microglobulinRR + α1 -acid glycoproteinRR - albuminRR )/6) were 43.7% with Helixone-HD, 47.7% with PMMA, 54% with polyphenylene, 54.8% with MCO and 59.6% with Helixone-HDF, with significant differences. In conclusion, this study confirms the superiority of OL-HDF over HD with the high-flux dialyzers that allow both treatments. Although new dialyzers with high permeability can only be used in HD, they are in an intermediate position and some are very close to OL-HDF.

Medium Cut-Off Dialyzer versus Eight Hemodiafiltration Dialyzers: Comparison Using a Global Removal Score.

BACKGROUND: A novel class of membranes, medium cut-off (MCO) membranes, has recently been designed to achieve interesting removal capacities for middle and large middle molecules in hemodialysis (HD) treatments. The few studies published to date have reported contradictory results regarding middle-sized molecules when comparing MCO dialyzers versus dialyzers used in online hemodiafiltration (OL-HDF). METHODS: A prospective, single-center study was carried out in 22 patients. Each patient underwent 9 dialysis sessions with routine dialysis parameters, one with an MCO dialyzer in HD and the other 8 with different dialyzers in OL-HDF. The removal ratio (RR) of urea, creatinine, ß2-microglobulin, myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein, and albumin was intraindividually compared. Albumin loss in dialysate was measured. We propose a global removal score ([ureaRR + ß2-microglobulinRR + myoglobinRR + prolactinRR + α1-microglobulinRR + α1-acid glycoproteinRR]/6 - albuminRR) as a new tool for measuring dialyzer effectiveness. RESULTS: No significant differences in the RRs of small and middle molecular range molecules were observed between the MCO vs. OL-HDF dialyzers (range 60-80%). Lower RRs were found for α1-microglobulin and α1-acid glycoprotein without significant differences. The albumin RR was < 11% and dialysate albumin loss was < 3.5 g in all situations without significant differences. The global removal score was 54.9 ± 4.8% with the MCO dialyzer without significant differences. CONCLUSIONS: Removal of a wide range of molecular weights, calculated with the proposed global removal score, was almost equal with the MCO dialyzer in HD treatment compared with 8 high-flux dialyzers in high-volume OL-HDF without relevant changes in albumin loss. The global removal score could be a new tool to evaluate the effectiveness of dialyzers and/or different treatment modalities.

Improved Control of Secondary Hyperparathyroidism in Hemodialysis Patients Switching from Oral Cinacalcet to Intravenous Etelcalcetide, Especially in Nonadherent Patients.

BACKGROUND: Etelcalcetide is a novel second-generation calcimimetic that, because of its intravenous administration, could improve treatment adherence in secondary hyperparathyroidism (SHPT). The aim of this study was to evaluate the effectiveness of etelcalcetide compared with that of cinacalcet in controlling SHPT in patients under hemodialysis. METHODS: A prospective observational study was performed in 29 patients with SHPT under hemodialysis who switched from cinacalcet to etelcalcetide with a follow-up of 6 months. A survey was conducted of adherence to the oral calcimimetic. The primary end-point of the study was to assess whether etelcalcetide was more effective than cinacalcet in controlling SHPT. RESULTS: After the switch of treatment, none of the patients developed clinical intolerance or new adverse effects. Etelcalcetide was more effective than cinacalcet in controlling intact parathyroid hormone (iPTH), with an overall decrease in iPTH levels that was significant from the second month. Average calcium levels remained within the normal range, with a higher percentage of hypocalcemia with etelcalcetide (6.9 vs. 13.8%), which was asymptomatic in all cases. Patients who were nonadherent to cinacalcet (38%) showed a significant reduction in calcium and iPTH during follow-up with etelcalcetide. The adherent group (62%) also showed a trend to lower iPTH levels reaching statistical significance after 5 months of follow-up. The dose conversion factor for the switch from cinacalcet to etelcalcetide was etelcalcetide/session = 0.111*mg cinacalcet/day + 0.96, R2 = 0.57. CONCLUSIONS: Etelcalcetide was more effective than cinacalcet in this patient population, especially in the nonadherent subgroup, leading to better SHPT control without adverse effects.

Hemodiafiltration versus conventional hemodialysis: Should "conventional" be redefined?

In the 1980s, conventional hemodialysis was considered as dialysis with acetate dialysate, dialysis machines without volumetric control, low blood flow and low-flux dialyzers; in the 1990s, the concept of conventional hemodialysis changed due to technological advances in dialysis machines, control of ultrafiltration and the widespread use of bicarbonate dialysate, which allowed an increase in blood flow and the use of synthetic high-flux dialyzers. To avoid backfiltration-induced adverse reactions, exogenous replacement fluid was promoted but its adoption was limited for technical and financial reasons. This scenario changed in 1995 with the development of on-line hemodiafiltration (HDF) techniques using the dialysis fluid itself as a replacement fluid. Dialysis machines were modified to perform on-line HDF, incorporating safety filters to ensure the quality of this replacement fluid (ultrapure dialysate). After more than two decades of clinical experience and technological development with high-volume HDF, the present article discusses whether HDF can currently be considered as the standard conventional treatment for chronic hemodialysis patients. A review of the evidence indicates that the time has come to consider HDF as the conventional hemodialysis treatment for the following reasons: first, technological development in water treatment and advances in dialysis machines, as well as the widespread use of synthetic high-flux dialyzers has made it a feasible proposition. Second, there is an absence of published literature showing any undesirable effects. Finally, scientific evidence is available showing the superiority of HDF over hemodialysis in overall and cardiovascular mortality in both prevalent and incident patients.