Publications by authors named "F Maduell"

127 Publications

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

Blood Purif 2021 Mar 31:1-9. Epub 2021 Mar 31.

Department of Nephrology, Hospital Clinic de Barcelona, Barcelona, Spain.

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 β2-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.
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http://dx.doi.org/10.1159/000514936DOI Listing
March 2021

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.

BMC Nephrol 2021 Feb 25;22(1):70. Epub 2021 Feb 25.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

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.
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http://dx.doi.org/10.1186/s12882-021-02265-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905891PMC
February 2021

Health Technology Assessment of a new water quality monitoring technology: Impact of automation, digitalization and remoteness in dialysis units.

PLoS One 2021 25;16(2):e0247450. Epub 2021 Feb 25.

Assessment of Innovations and New Technologies Unit, Hospital Clínic Barcelona, University of Barcelona, Barcelona, Catalonia, Spain.

Background: Water quality monitoring at the dialysis units (DU) is essential to ensure an appropriate dialysis fluid quality and guarantee an optimal and safe dialysis treatment to patients. This paper aims to evaluate the effectiveness, economic and organizational impact of automation, digitalization and remote water quality monitoring, through a New Water Technology (NWT) at a hospital DU to produce dialysis water, compared to a Conventional Water Technology (CWT).

Methods: A before-and-after study was carried out at the Hospital Clínic Barcelona. Data on CWT was collected during 1-year (control) and 7-month for the NWT (case). Data on water quality, resource use and unit cost were retrospective and prospectively collected. A comparative effectiveness analysis on the compliance rate of quality water parameters with the international guidelines between the NWT and the CWT was conducted. This was followed by a cost-minimization analysis and an organizational impact from the hospital perspective. An extensive deterministic sensitivity analysis was also performed.

Results: The NWT compared to the CWT showed no differences on effectiveness measured as the compliance rate on international requirements on water quality (100% vs. 100%), but the NWT yielded savings of 3,599 EUR/year compared to the CWT. The NWT offered more data accuracy (daily measures: 6 vs. 1 and missing data: 0 vs. 20 days/year), optimization of the DU employees' workload (attendance to DU: 4 vs. 19 days/month) and workflow, through the remote and continuous monitoring, reliability of data and process regarding audits for quality control.

Conclusions: While the compliance of international recommendations on continuous monitoring was performed with the CWT, the NWT was efficient compared to the CWT, mainly due to the travel time needed by the technical operator to attend the DU. These results were scalable to other economic contexts. Nonetheless, they should be taken with caution either when the NWT equipment/maintenance cost are largely increased, or the workforce involvement is diminished.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247450PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906308PMC
February 2021

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

Blood Purif 2020 Dec 22:1-8. Epub 2020 Dec 22.

Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1159/000510557DOI Listing
December 2020

Detection and significance of green inclusions in peripheral blood neutrophils and monocytes.

Int J Lab Hematol 2021 Apr 8;43(2):e92-e94. Epub 2020 Dec 8.

Medical Intensive Care Unit, Department of Medicine, Hospital Clinic de Barcelona-IDIBAPS, University of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/ijlh.13421DOI Listing
April 2021

Assessment of removal and adsorption enhancement of high-flux hemodialyzers in convective therapies by a novel in vitro uremic matrix.

Sci Rep 2020 10 15;10(1):17403. Epub 2020 Oct 15.

Department of Nephrology, Hospital Clínic de Barcelona, Barcelona, Spain.

Adsorption properties of hemodialyzers are traditionally retrieved from diffusive treatments and mainly focused on inflammatory markers and plasma proteins. The possible depurative enhancement of middle and high molecular weight solutes, as well as protein-bound uremic toxins by adsorption in convective treatments, is not yet reported. We used discarded plasma exchanges from uremic patients and out-of-date erythrocytes as a novel in vitro uremic precursor matrix to assess removal and adsorption patterns of distinct material and structure but similar surface hemodialyzers in hemodialysis and on-line hemodiafiltration treatments. We further related the obtained results to the possible underlying membrane pore blocking mechanisms. Convection improved removal but slightly enhanced adsorption in the cellulosic and synthetic dialyzers tested. The polymethylmethacrylate hemodialyzer obtained the highest extracted ([Formula: see text]) and adsorbed ([Formula: see text]) mass values when submitted to hemodiafiltration for all molecules analyzed including albumin ([Formula: see text] g, [Formula: see text] mg), whereas the polyamide membrane obtained substantial lower results even for this molecule ([Formula: see text] g, [Formula: see text] mg) under the same treatment parameters. Hemodiafiltration in symmetric and enlarged pore hemodialyzers enhances removal and adsorption by internal pore deposition (intermediate pore-blocking) for middle and high molecular weight toxins but leads to substantial and deleterious albumin depuration.
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http://dx.doi.org/10.1038/s41598-020-74528-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562951PMC
October 2020

Prevalence of COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening.

J Am Soc Nephrol 2020 12 29;31(12):2966-2967. Epub 2020 Sep 29.

Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1681/ASN.2020081193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790200PMC
December 2020

Impact of locking solutions on conditioning biofilm formation in tunnelled haemodialysis catheters and inflammatory response activation.

J Vasc Access 2020 Jul 21:1129729820942040. Epub 2020 Jul 21.

Department of Nephrology, Hospital Clínic de Barcelona, Barcelona, Spain.

Introduction: The surface of tunnelled cuffed catheters provides an optimal environment for the development of biofilms, which have recently been described as conditioning films because of the presence of adherent biological materials. These biofilms are associated with infection and thrombosis and potentially increase patients' inflammatory response. These complications could be reduced by the use of locking solutions.

Objective: To analyse biofilm formation, using confocal and electron microscopy, in tunnelled cuffed catheters locked with three different solutions and to determine the relationship between these solutions and inflammatory response.

Study Design: This prospective study included 35 haemodialysis patients with tunnelled cuffed catheter removal for non-infection-related reasons. The participants were divided into three groups according to the lock solution used: (1) heparin 1: 5000 IU; (2) citrate 4%; and (3) taurolidine 1.35%, citrate 4% and heparin 500 IU (taurolock); in the latter group, 25,000 IU taurolidine-urokinase was used in the last weekly session. All tunnelled cuffed catheters were cultured, and the inner surface was evaluated with confocal and electron microscopy. The inflammatory profile of included patients was determined at tunnelled cuffed catheter removal.

Results: There were no differences in clinical or demographic variables between the three subgroups. Biofilm thickness was lower in the taurolidine group than in the citrate 4% and heparin groups (28.85 ± 6.86 vs 49.99 ± 16.56 vs 56.2 ± 15.67 µm, respectively;  < 0.001), as was biofilm volume (1.01 ±1.18 vs 3.7 ± 2.15 vs 5.55 ±2.44, µm, respectively;  < 0.001). The mean interleukin-6 value was 39%, which was 50% lower than in the citrate and heparin groups, but without significance differences.

Conclusion: Our results show that biofilms were found in all tunnelled cuffed catheters, but the thickness and volume were significantly lower in tunnelled cuffed catheters locked with taurolidine solution. Therefore, the type of locking solution used in tunnelled cuffed catheters should maintain tunnelled cuffed catheter sterility and prevent catheter-related bloodstream infections. No significant difference was observed in the inflammatory profile according to the type of locking solution.
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http://dx.doi.org/10.1177/1129729820942040DOI Listing
July 2020

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

Artif Organs 2020 Oct 5;44(10):E448-E458. Epub 2020 May 5.

Department of Biochemistry, Hospital Clínic Barcelona, Barcelona, Spain.

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 (Q ), 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, ß -microglobulin, myoglobin, prolactin, α -microglobulin, α -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 (R  = 0.583) and with Qb 400 (R  = 0.584); with Q with Qb 350 (R  = 0.556) and with Qb 400 (R  = 0.604); and also with FF with Qb 350 (R  = 0.556) and with Qb 400 mL/min (R  = 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 Q 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, Q , or FF exceeds certain values. Increasing the Qb in postdilution HDF manages to increase the convective dose and more easily overcome the HDx.
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http://dx.doi.org/10.1111/aor.13700DOI Listing
October 2020

Long-Term Peridialytic Blood Pressure Patterns in Patients Treated by Hemodialysis and Hemodiafiltration.

Kidney Int Rep 2020 Apr 31;5(4):503-510. Epub 2020 Jan 31.

Department of Nephrology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, VU University, Amsterdam, the Netherlands.

Introduction: Online postdilution hemodiafiltration (HDF) is associated with a lower all-cause and cardiovascular mortality than hemodialysis (HD). This may depend on a superior peridialytic (pre- and postdialysis, and the difference between these 2 parameters) hemodynamic profile.

Methods: In this retrospective cohort analysis of individual participant data (IPD) from 3 randomized controlled trials (RCTs) ( = 2011), the effect of HDF and HD on 2-year peridialytic blood pressure (BP) patterns was assessed. Long-term peridialytic systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP), as well as the deltas (post- minus predialytic) were assessed in the total group of patients. Thereafter, these variables were compared between patients on HD and HDF, and in the latter group between quartiles of convection volume.

Results: Mean pre- and postdialysis SBP, DBP, and MAP declined significantly during follow-up (predialytic: SBP -2.16 mm Hg, DBP -2.88 mm Hg, MAP -2.64 mm Hg), PP increased (predialytic 0.96 mm Hg). Peridialytic deltas remained unaltered. Differences between the 2 modalities, or between quartiles of convection volume were not observed. BP changes were independent of various baseline characteristics, including the decline in body weight over time.

Conclusion: We speculate that the combination of a decreasing SBP and an increasing PP may be the clinical sequelae of a worsening cardiovascular system. Because especially HDF with a high convection volume has been associated with a beneficial effect on survival, our study does not support the view that superior peridialytic BP control contributes to this effect.
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http://dx.doi.org/10.1016/j.ekir.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136332PMC
April 2020

Green inclusions in neutrophils: A critical finding that must be reported.

Int J Lab Hematol 2020 06 24;42(3):e101-e104. Epub 2019 Dec 24.

Biochemistry and Molecular Genetics Department, Core Laboratory, Biomedical Diagnostic Center, Hospital Clinic of Barcelona, Barcelona, Spain.

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http://dx.doi.org/10.1111/ijlh.13138DOI Listing
June 2020

Study of Biocompatibility of Membranes in Online Hemodiafiltration.

Blood Purif 2020 19;49(4):400-408. Epub 2019 Dec 19.

Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain,

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.
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http://dx.doi.org/10.1159/000504954DOI Listing
December 2019

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.

Artif Organs 2020 May 22;44(5):513-521. Epub 2019 Dec 22.

Nephrology Department, Hospital Clínic de Barcelona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1111/aor.13603DOI Listing
May 2020

Comparison of Solute Removal Properties Between High-Efficient Dialysis Modalities in Low Blood Flow Rate.

Ther Apher Dial 2020 Aug 10;24(4):387-392. Epub 2019 Nov 10.

Department of Biochemistry, Hospital Clínic Barcelona, Barcelona, Spain.

Blood flow (Qb) is one of the dialysis parameters most strongly influencing the performance of dialysis modalities. However, few studies have compared different dialysis modalities in patients with low Qb. We conducted a prospective, single-center study in 21 patients. Each patient underwent four dialysis sessions with routine dialysis parameters: high-flux hemodialysis (HD), predilution hemodiafiltration (pre-HDF), expanded HD (HDx), and postdilution HDF (post-HDF). The removal ratios (RR) of urea, creatinine, ß -microglobulin, myoglobin, prolactin, α -microglobulin, free kappa and lambda immunoglobulin light chains (ķFLC and λFLC), α -acid glycoprotein, and albumin were compared intraindividually. A proportional part of the dialysate was collected to quantify albumin loss. There were no differences in urea and creatinine RRs. The β -microglobulin RR was higher in pre-HDF and post-HDF. Myoglobin and prolactin RRs were higher with HDx and post-HDF. The α -microglobulin and α -acid glycoprotein RRs were significantly higher with post-HDF than with other treatments, and RRs obtained with HDx were higher than obtained with HD and pre-HDF. Free ķFLC and λFLC RRs showed the following results in ascending order: HD, pre-HDF, HDx, and post-HDF, most of them with statistical significance. Albumin loss varied from 0.45 g with HD to 3.5 g with post-HDF. The global removal score values were 41.0 ± 4.8% with HD, 44.0 ± 5.2% with pre-HDF, 49.5 ± 4.6% with HDx, and 54.8 ± 5.3% with post-HDF, with significant differences between all treatment modalities. In conclusion, this study confirms the superiority of post-HDF over high-flux HD, pre-HDF, and HDx in patients with low Qb. HDx was the closest alternative to post-HDF and was clearly superior to HD and pre-HDF. Finally, pre-HDF was also superior to HD. With this Qb, there was a higher risk of underdialysis, both diffusive and convective, especially in patients with a session duration of less than 5 h.
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http://dx.doi.org/10.1111/1744-9987.13440DOI Listing
August 2020

Are Currently Used Bioimpedance Methods in Hemodialysis Comparable for Calculating Dialysis Dose?

Ther Apher Dial 2020 Apr 20;24(2):154-162. Epub 2019 Nov 20.

Hospital Clinic Barcelona - Nephrology and Renal Transplantation, Barcelona, Spain.

Bioelectrical impedance analysis has increasingly been incorporated into hemodialysis units (HD) as a useful, noninvasive technique for evaluating overall fluid status. The aims of this study were to verify whether the information obtained from two different bioelectrical impedance analysis methods (spectroscopy bioimpedance [BCM] and single-frequency bioelectric impedance vector analysis [SF-BIVA]) was comparable for analyzing fluid status, and to determine their impact when used to calculate dialysis dose. This observational cross-sectional study included 78 HD patients who underwent one measurement with BCM and one with SF-BIVA in the same dialysis session. For calculating the dialysis dose, total body water or urea distribution volume (V) was calculated by the Watson formula and compared with the V obtained from the two devices. The difference in V between the two devices was 5.4 L (P < 0.001). Given the existent correlation between V and V , we were able to apply a formula (corrected V = V = 1.04 × V + 4.85, r = 0.93), allowing comparison of the two bioimpedance methods. The mean dialysis dose for BCM device (Kt /V ) was 2.49 ± 0.85, much higher than Kt /V (2.06 ± 0.72) mainly due to the V obtained with the different devices, with Kt /V being 2.03 ± 0.67. The results on volume distribution showed an acceptable correlation but the devices were not comparable due to intermethod differences observed. Dialysis centers using SF-BIVA will obtain much lower dialysis dose, but by applying our formula, the Kt/V would resemble that obtained by the BCM device.
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http://dx.doi.org/10.1111/1744-9987.13424DOI Listing
April 2020

Evaluation of the influence of the surface membrane and blood flow in medium «cut-off» (MCO) dialyzers.

Nefrologia 2019 Nov - Dec;39(6):623-628. Epub 2019 May 16.

Servicio Bioquímica, Hospital Clínic de Barcelona, Barcelona, España.

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 m, and/or the Qb (300, 350, 400 or 450mL/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 β-microglobulin, myoglobin, prolactin, α-microglobulin and α-acid glycoprotein, except for some comparison with Qb 450mL/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 m 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.
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http://dx.doi.org/10.1016/j.nefro.2019.02.006DOI Listing
September 2020

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

Artif Organs 2019 Oct 18;43(10):1014-1021. Epub 2019 Jun 18.

Department of Biochemistry, Hospital Clínic Barcelona, Barcelona, Spain.

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, ß -microglobulin, myoglobin, prolactin, α -microglobulin, α -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 β -microglobulin, myoglobin and prolactin RRs with Helixone-HDF treatment were significantly higher than those obtained with all 4 dialyzers in HD treatment. The β -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 α -microglobulin and α - 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 ((Urea + β -microglobulin + myoglobin + prolactin + α -microglobulin + α -acid glycoprotein - albumin )/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.
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http://dx.doi.org/10.1111/aor.13480DOI Listing
October 2019

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

Blood Purif 2019 3;48(2):167-174. Epub 2019 Apr 3.

Department of Biochemistry, Hospital Clínic Barcelona, Barcelona, Spain.

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, β2-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 + β2-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.
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http://dx.doi.org/10.1159/000499759DOI Listing
January 2020

Brachiobasilic arteriovenous fistula with superficialisation and transposition the basilic vein in a one stage surgical technique. Five years of single experience.

Nefrologia 2019 Jul - Aug;39(4):388-394. Epub 2019 Mar 8.

Servicio de Nefrología, Hospital Clínic; Unidad Funcional de Acceso Vascular, Barcelona, España.

Background: The basilic vein is a deep vein which usually requires superficialisation and surgical transposition.

Material And Methods: This is a retrospective study of 119 BBAVF-ST in patients with stage 5D chronic kidney disease who received an implant with a one-stage surgical technique (2011-2015). The percentage of primary (PP), assisted primary (APP) and secondary (SP) permeabilities were assessed, as well as the related complications. We analysed the permeabilities using Kaplan-Meier survival curves and a univariate Log Rank analysis (Mantel-Cox). P values less than or equal to 0.05 were considered as significant.

Results: The mean age of the study group was 67.9years, with 63.8% of the subjects being male. A total of 57 complications were detected during the follow-up period: 24 stenosis (42.1%), 11 thrombosis (19.2%), 7 vascular access steal syndromes (12.2%), 7 upper limb oedemas (12.2%), 6 post-puncture haematomas (10.5%) and 2 infections (3.5%). The percentages of PP obtained at 1, 6, 12 and 24months were 92.4%, 79.8%, 66.3% and 52%; APP: 94.1%, 87.3%, 80.4% and 65.6%, and SP: 95%, 89.1%, 84% and 67.5%, respectively. Diabetic patients presented with significantly worse permeabilities than vascular or idiopathic patients: (P=.037, .009 and .019, respectively).

Conclusions: According to the results obtained in our study, the one-stage surgical implementation of BBAVF-ST presents high permeability rates and a small number of related complications. Diabetes mellitus is a factor related to a worse surgical prognosis. Some of the biggest advantages are the greater optimisation of health resources and a shorter time in which the central venous catheter needs to remain in the body.
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http://dx.doi.org/10.1016/j.nefro.2018.11.010DOI Listing
May 2020

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

Blood Purif 2019 30;48(2):106-114. Epub 2019 Jan 30.

Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, Barcelona, Spain,

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.
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http://dx.doi.org/10.1159/000496562DOI Listing
January 2020

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

Artif Organs 2019 Mar 15;43(3):261-269. Epub 2018 Nov 15.

Nephrology and Renal Transplantation Department, Hospital Clinic Barcelona, Barcelona, Spain.

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 β -microglobulin were measured. The patients' hydration status was evaluated by bioimpedance analysis. The mean of vancomycin dialyzer clearance (Kd ) 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 β -microglobulin clearance, Kd 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 (Kd ), extraction mass (M ), and inter-compartment mass-transfer coefficient (K ) of each molecule. A higher vancomycin Kd 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.
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http://dx.doi.org/10.1111/aor.13368DOI Listing
March 2019

Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia.

Gastroenterol Hepatol 2019 Mar 4;42(3):164-170. Epub 2018 Oct 4.

Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain. Electronic address:

Introduction: In the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes.

Patients And Methods: This is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014-2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed.

Results: All patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose.

Conclusion: HCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.
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http://dx.doi.org/10.1016/j.gastrohep.2018.07.015DOI Listing
March 2019

A unidimensional diffusion model applied to uremic toxin kinetics in haemodiafiltration treatments.

Math Med Biol 2019 06;36(2):223-240

Department of Nephrology and Renal Transplantation, Institut Clínic de Nefrologia i Urologia (ICNU), Hospital Clínic de Barcelona, Villaroel, Barcelona, Spain.

Kinetic modelling in haemodialysis is usually based upon the resolution of volume-defined compartment models. The interaction among these compartments is described by purely diffusive processes. In this paper we present an alternative kinetic model for uremic toxins in post-dilutional haemodiafiltration treatments by means of a unidimensional diffusion equation. A wide range of solutes such as urea, creatinine, $\beta _{2}$-microglobulin, myoglobin and prolactin were studied by imposing appropriate boundary and initial conditions in a virtual [0,1] domain. The diffusivity along the domain and the extraction rate at the dialyser are the kinetic parameters which were fitted by least-squares for every studied solute. The accuracy of the presented volumeless model as well as the behavior of the proposed kinetic parameters could be an alternative to the compartment description for a variety of molecular weight uremic toxins undergoing different treatment configurations.
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http://dx.doi.org/10.1093/imammb/dqy008DOI Listing
June 2019

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

Semin Dial 2018 11 29;31(6):625-632. Epub 2018 May 29.

Department of Nephrology, Hospital Clínic Barcelona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1111/sdi.12715DOI Listing
November 2018

Bioimpedance Spectroscopy as a Practical Tool for the Early Detection and Prevention of Protein-Energy Wasting in Hemodialysis Patients.

J Ren Nutr 2018 09 22;28(5):324-332. Epub 2018 Apr 22.

Nephrology and Renal Transplantation, Hospital Clinic Barcelona, Barcelona, Spain.

Objectives: To evaluate whether body composition monitor (BCM) could be a practical instrument for nephrologists to assess nutritional status in patients on hemodialysis (HD) and whether it is more effective in identifying patients at highest risk of developing protein-energy wasting (PEW) alone or in combination with other tools currently used for that purpose.

Design: Observational cross-sectional study in 91 HD patients (60 ± 14 years, 70.3% male, 24 ± 4.1 kg/m body mass index) from 2 different locations.

Methods: Nutritional status was evaluated by anthropometric methods (biceps and triceps skinfold thickness, waist circumference, and arm muscular circumference), biochemical nutritional markers, malnutrition-inflammation score (MIS), and BCM. The patients were grouped into those with and without PEW by using classical criteria and then classified as being adequately or inadequately nourished according to a BCM flow chart to detect those requiring preferential nutritional intervention. A multivariate approach was used to calculate the risk of developing PEW.

Results: Anthropometric measurements revealed significantly lower body mass index (<23 kg/m; odds ratios [OR] = 13.3 and P = 0.001) and arm muscular circumference < p10 (OR = 34, P < 0.001) in the PEW group. MIS was above 5 in all the patients classified as having PEW. BCM showed that fat tissue index < p10 was significantly lower in this group (OR = 1.52), and a decision tree using the lean tissue index < p10, fat tissue index < p10, and extracellular water > 15% revealed that 42.9% of the patients would need nutritional monitoring. On multivariate analysis, insufficient nutritional status detected by BCM decision tree was an independent prognostic factor for developing PEW. About 9.89% of the patients were classified as PEW, with MIS > 5, and insufficient nutritional status detected by BCM required preferential nutritional intervention.

Conclusion: BCM is a practical instrument for nephrologists to assess nutritional status in patients on HD and is useful for the early prevention and detection of PEW, as is able to identify differences in body composition, predict clinically important outcomes, and classify patients requiring preferential nutritional intervention.
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http://dx.doi.org/10.1053/j.jrn.2018.02.004DOI Listing
September 2018

SNF472, a novel inhibitor of vascular calcification, could be administered during hemodialysis to attain potentially therapeutic phytate levels.

J Nephrol 2018 04 19;31(2):287-296. Epub 2018 Jan 19.

Nephrology and Renal Transplantation, Hospital Clínic, Barcelona, Spain.

Background: Cardiovascular calcification (CVC) is a major concern in hemodialysis (HD) and the loss of endogenous modulators of calcification seems involved in the process. Phytate is an endogenous crystallization inhibitor and its low molecular mass and high water solubility make it potentially dialyzable. SNF472 (the hexasodium salt of phytate) is being developed for the treatment of calciphylaxis and CVC in HD patients. We aimed to verify if phytate is lost during dialysis, and evaluate SNF472's behaviour during dialysis.

Methods: Dialyzability was assessed in vitro using online-hemodiafiltration and high-flux HD systems in blood and saline. SNF472 was infused for 20 min and quantified at different time points.

Results: Phytate completely dialyzed in 1 h at low concentrations (10 mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions, calcium was slightly chelated during SNF472 infusion but when the system was switched to dialysis mode the calcium in the bath compensated this chelation.

Conclusion: Phytate dialyses with a low clearance. The administration of SNF472 as an exogenous source of phytate allows to attain supra-physiological levels required for its potential therapeutic properties. As SNF472 is infused during the whole dialysis session, the low clearance would not affect the drug's systemic exposure.
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http://dx.doi.org/10.1007/s40620-018-0471-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829128PMC
April 2018

Evaluation of the dialyser inner diameter in online haemodiafiltration.

Nefrologia 2018 Jan - Feb;38(1):34-40

Servicio de Bioquímica, Hospital Clínic, Barcelona, España.

Introduction: Online haemodiafiltration (OL-HDF) has been associated with increased survival. To date, the influence of the inner diameter of the hollow fibres of the dialyser on convective volume has not been well established. The objective of the study was to evaluate the effect of increasing the inner diameter of the dialyser on the convective volume and removal capacity.

Material And Methods: We included 16 patients in posdilutional OL-HDF with autosubstitution. Each patient was analysed in 4 sessions in which the inner diameter varied; 185μm (FX60 Cordiax and FX80 Cordiax) versus 210μm (FX600 Cordiax and FX800 Cordiax). Different solutes were measured at the beginning and end of each dialysis session.

Results: No differences in the convective volume were found with an increased inner diameter: 32.3±3.1 vs. 31.8±3.6 l/session (FX60 vs. FX600) and 33.7±4.3 vs. 33.5±3.8 l/session (FX80 vs. FX800). The reduction percentages also did not differ: urea 83.7±4.5 vs. 84.1±3.4 for FX60 and FX600, and 82.7±4.1 vs. 83.6±3.8 for FX80 vs. FX800; creatinine similar 78.2±5.6 vs. 77.8±4.6 y 77.1±5.4 vs. 78.1±4.9; β-microglobulin 82.2±4.3 vs. 82.9±4.2, and 82.9±4.7 vs. 84.0±3.8; myoglobin 71.0±10 vs. 70.2±9 and 72.8±11 vs. 75.0±10; prolactin 70.4±9 vs. 68.1±9, and 72.2±10 vs. 73.4±8.2; and α-microglobulin 22.9±10 vs. 21.6±10, and 26.5±12 vs. 28.8±11, respectively.

Conclusion: The increase in the inner diameter of the hollow fibres did not result in improved convective volume and removal capacity.
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http://dx.doi.org/10.1016/j.nefro.2017.03.013DOI Listing
October 2018