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.

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.

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.

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.

Multi-site performance evaluation and Sigma metrics of 20 assays on the Atellica chemistry and immunoassay analyzers.

Background The Atellica Solution comprises chemistry (CH) and immunoassay (IM) analyzers. Recently, six early adopter clinical laboratories across Europe evaluated the analytical performance of 20 CH and IM assays. To measure analytical performance quality, Sigma metrics were calculated for individual-site and pooled-site results. Methods Precision, detection capability, linearity, and method comparison studies were performed according to Clinical Laboratory Standards Institute protocols. Global Sigma metrics across sites were calculated from pooled data at the medical decision level using total allowable error (TEa) goals from CLIA for CH assays, and TEa goals from RiliBÄK for IM assays; and, the equation: Sigma metrics=%TEa-%bias/%CV. A pooled %CV was calculated by combining the imprecision obtained from individual sites. Bias calculations were performed against the ADVIA Chemistry system or ADVIA Centaur system using Deming regression analysis (Passing-Bablok regression for electrolytes) on the pooled-site data. The 103 individual-site Sigma metric calculations used individual-site imprecision and pooled-bias. Results The limits of blank and detection results agreed with the manufacturer's claims. Most assays were linear across the assay range tested. Pooled Sigma metrics were good or better (>4 Sigma) for 18 of 20 assays; and, acceptable for urea nitrogen (3.1) and sodium (3.9), the latter values attributable to higher imprecision at one of five sites. Conclusions Sigma metrics for data generated across multiple real-world sites evaluating the Atellica Solution demonstrated good or better performance of greater than 4 Sigma for 18 of 20 assays tested. Overall, results verified the manufacturer's claims that methods were fit for use in clinical laboratories.

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.

Mathematical Modeling of Different Molecule Removal on On-Line Haemodiafiltration: Influence of Dialysis Duration and Infusion Flow.

BACKGROUND: In a previous study on a nocturnal, every-other-day online haemodiafiltration scheme, different removal patterns were observed for urea, creatinine, ß2-​microglobulin, myoglobin and prolactin. The aim of this study was to evaluate the influence of dialysis duration and infusion flow (Qi) on the removal of different molecular weight (MW) solutes, and to quantify the effect of the different treatments on the kinetics of the solutes by using a classical two-compartment model. METHODS: This prospective, in-center study was carried out in 10 patients on a nocturnal, every-other-day online post-dilution haemodiafiltration program. Each patient received four dialysis sessions with different conditions, two 4-h sessions (with infusion flows of 50 or 100 ml/min) and two 8-h sessions (with infusion flows of 50 or 100 ml/min). To analyze the solute kinetics, blood samples were obtained hourly during the dialysis treatments and in the first 3 h post-dialysis. RESULTS: Removal patterns differed in the molecules studied, which were quantified by means of the two-compartment mathematical model. The main results show the impact of dialysis duration on the removal of low molecular weight molecules (urea and creatinine), while the impact of Qi is clearly shown for high molecular weight molecules (myoglobin and prolactin). For middle molecular weight solutes, such as ß2-microglobulin, both factors (duration and Qi) enhance the removal efficiency of the dialyzer. CONCLUSIONS: Our study evaluates experimentally and mathematically how treatment time and infusion flow affect the filtration of solutes of different MW during post-dilution haemodiafiltration. The results provided by the present study should help physicians to select and individualise the most appropriate schedules to deliver an optimum diffusive and convective dialysis dose for each patient.

Comparison of efficacy and safety of the new generation helixone dialyzers.

INTRODUCTION: New generation helixone dialyzers has recently been developed as part of the ongoing effort to improve dialyzer hemocompatibility and avoid adverse reactions to synthetic dialyzers. This study aimed to assess the performance and albumin loss of this new dialyzer series in hemodiafiltration and compare it with the previous generation helixone series. MATERIAL AND METHODS: A prospective study was conducted in 19 patients. Each patient underwent eight dialysis sessions with the same routine dialysis parameters; only the dialyzer varied: FX60 CorDiax, FX CorAL 60, FX600 CorDiax, FX CorAL 600, FX80 CorDiax, FX CorAL 80, FX800 CorDiax, and FX CorAL 800. The reduction ratios (RR) of urea, creatinine, ß2-microglobulin, myoglobin, kappa-free immunoglobulin light chains (κFLC), prolactin, α1-microglobulin, α1-acid glycoprotein, lambda immunoglobulin light chains (λFLC), and albumin were compared intra-individually. Dialysate albumin loss was also measured. RESULTS: All treatments were well tolerated. The mean amount of replacement fluid ranged from 31 to 34 L. Comparison of dialysis treatments showed no differences between small molecules and even up to those the size of ß2-microglobulins. Little differences were found between myoglobin, κFLC, prolactin, α1-microglobulin, and λFLC RRs, and only FX80 CorDiax was slightly superior to the others. Mean dialysate albumin losses were similar, with less than 2.5 g lost in each dialyzer. The FX80 CorDiax showed slightly higher global removal scores than the other dialyzers evaluated, except for FX CorAL 800. CONCLUSION: The new generation helixone dialyzers series has been updated to minimise the risk of adverse reactions, while maintaining the effectiveness and albumin loss achieved by the previous most advanced helixone generation.

Nocturnal, every-other-day, online haemodiafiltration: an effective therapeutic alternative.

BACKGROUND: Longer and more frequent dialysis sessions have demonstrated excellent survival and clinical advantages, while online haemodiafiltration (OL-HDF) provides the most efficient form of dialysis treatment. The aim of this study was to evaluate the beneficial effects of a longer (nocturnal) and more frequent (every-other-day) dialysis schedule with OL-HDF at the same or the highest convective volume. METHODS: This prospective, in-centre crossover study was carried out in 26 patients, 18 males and 8 females, 49.2±14 years old, on 4-5 h thrice-weekly post-dilution OL-HDF, switched to nocturnal every-other-day OL-HDF. Patient inclusion criteria consisted of stable patients with good vascular access and with good prospects for improved occupational, psychological and social rehabilitation. Patients were randomly assigned into two groups: Group A received the same convective volume as previously for 6 months followed by a higher convective volume for a further 6 months, while Group B received the same schedule in reverse order. RESULTS: Nocturnal every-other-day OL-HDF was well tolerated and 56% of patients who were working during the baseline period continued to work throughout the study with practically no absenteeism. The convective volume was 26.7±2 L at baseline, 27.5±2 with the unchanged volume and 42.9±4 L with the higher volume. eKt/V increased from 1.75±0.4 to 3.37±0.9. Bicarbonate, blood urea nitrogen (BUN) and creatinine values decreased, while phosphate levels fell markedly with a 90% reduction in phosphate binders. Blood pressure and left ventricular hypertrophy (LVH) improved and the use of anti-hypertensive drugs decreased. In both groups, BUN, creatinine and ß2-microglobulin reduction ratios improved. Different removal patterns were observed for myoglobin, prolactin and α1-acid glycoprotein. CONCLUSIONS: Nocturnal every-other-day OL-HDF could be an excellent therapeutic alternative since good tolerance and occupational rehabilitation, marked improvement in dialysis dose, nutritional status, LVH, phosphate and hypertension control and a substantial reduction in drug requirements were observed. In this crossover study, different removal patterns of large solutes were identified.

Comparison of four medium cut-off dialyzers.

Background: Recently, several pharmaceutical companies have developed new medium cut-off (MCO) dialyzers for expanded hemodialysis (HDx). This study aimed to compare the safety and efficacy of four MCO dialyzers, against each other and versus high-flux hemodialysis (HD) and post-dilution hemodiafiltration (HDF). Methods: A prospective study was carried out on 23 patients who underwent six dialysis sessions: two sessions with the FX80 Cordiax in HD and HDF, and four HDx sessions with the Phylther 17-SD, Vie-18X, Elisio HX19 and Theranova 400 dialyzers. The reduction ratios (RRs) of urea, creatinine, ß2-microglobulin, myoglobin, kappa free immunoglobulin light chain (κFLC), prolactin, α1-microglobulin, α1-acid glycoprotein, lambda (λFLC) and albumin were compared. Dialysate albumin loss was also measured. Results: The differences in efficacy between the evaluated dialyzers were minimal in small molecules and even up to the size of ß2-microglobulin. The main differences were found between myoglobin, κFLC, prolactin, α1-microglobulin and λFLC RRs, in which all four MCO dialyzers, with similar efficacy, were clearly superior to HD and slightly inferior to HDF treatment. Albumin losses in the dialysate with HD dialyzers were <1 g and between 1.5 and 2.5 g in HDx and HDF. The global removal score values were similar in all four HDx treatments, and again significantly higher than those with HD. Conclusions: The results of the four MCO dialyzers evaluated in this study showed good efficiency, with no significant performance differences between them while being completely safe in terms of albumin loss. Likewise, the study confirms the superiority of HDx over high-flux HD with an efficacy close to that of post-dilution HDF.

Performance evaluation of the high sensitive troponin I assay on the Atellica IM analyser.

Introduction: The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe. Materials and methods: Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer's cut-offs. Sample turnaround time (TAT) was examined. Results: Imprecision repeatability CVs were 1.1-4.7% and within-lab imprecision were 1.8-7.6% (10.0-25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer's values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV). Conclusions: Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.

Analytical performance assessment and improvement by means of the Failure mode and effect analysis (FMEA).

INTRODUCTION: Laboratories minimize risks through quality control but analytical errors still occur. Risk management can improve the quality of processes and increase patient safety. This study aims to use the failure mode and effect analysis (FMEA) to assess the analytical performance and measure the effectiveness of the risk mitigation actions implemented. MATERIALS AND METHODS: The measurands to be included in the study were selected based on the measurement errors obtained by participating in an External Quality Assessment (EQA) Scheme. These EQA results were used to perform an FMEA of the year 2017, providing a risk priority number that was converted into a Sigma value (σFMEA). A root-cause analysis was done when σFMEA was lower than 3. Once the causes were determined, corrective measures were implemented. An FMEA of 2018 was carried out to verify the effectiveness of the actions taken. RESULTS: The FMEA of 2017 showed that alkaline phosphatase (ALP) and sodium (Na) presented a σFMEA of less than 3. The FMEA of 2018 revealed that none of the measurands presented a σFMEA below 3 and that σFMEA for ALP and Na had increased. CONCLUSIONS: Failure mode and effect analysis is a useful tool to assess the analytical performance, solve problems and evaluate the effectiveness of the actions taken. Moreover, the proposed methodology allows to standardize the scoring of the scales, as well as the evaluation and prioritization of risks.

Fortifier selection and dosage enables control of breast milk osmolarity.

BACKGROUND: Human breast milk (BM) fortification is required to feed preterm newborns with less than 32 weeks of gestation. However, addition of fortifiers increases osmolarity and osmolarity values higher than 450 mOsm/kg may be related to gastrointestinal pathology. Hence, fortifier selection and dosage are key to achieve optimal feeding. OBJECTIVES: To compare the effect on osmolality of adding different fortifications, including recently developed formulations, to BM and to study evolution of osmolarity over time in supplemented BM. METHODS: Frozen mature BM from 10 healthy mothers of premature newborns was fortified with each of the following human milk fortifiers (HMF): AlmirónFortifier®, NANFM85®, or PreNANFM85®. In addition, fortified BMs were modified with one of the following nutritional supplements (NS): Duocal MCT®, Nutricia® AminoAcids Mix, or Maxijul®. Osmolality of BM alone, fortified and/or supplemented was measured at 1 and 22 hours after their preparation. All samples were kept at 4°C throughout the study. RESULTS: Osmolality of BM alone was close to 300 mOsm/kg and did not change over 22 hours. When equicaloric amounts of HMF AlmirónFortifier®, NANFM85®, and PreNANFM85® were added to BM, osmolality increased roughly to 480 mOsm/kg with the first two fortifiers and only to 433±6 mOsm/kg with the third one. Upon addition of any of four different NSs to BM modified with AlmirónFortifier® and NANFM85®, osmolality reached values greater than 520 mOsm/kg, while osmolality of PreNANFM85® with two out of the four NSs remained below 490 mOsm/kg. NSs supplementing carbohydrates and hydrolysed proteins resulted into a higher increase of BM osmolarity. Osmolality increased significantly with time and, after 22h, only BM modified with PreNANFM85® remained below 450 mOsm/kg. CONCLUSIONS: Upon addition of the HMFs tested, BM osmolality increases significantly and keeps raising over time. All HMFs but the recently developed PreNAN FM85® at 4% exceed the AAP recommended threshold for osmolarity of 450 mOsm/kg. Addition of NSs to PreNAN FM85® at 4% significantly increases osmolality above 450 mOsm/Kg. Thus, using PreNAN FM85® at 5% may be preferable to adding nutritional supplements since nutritional recommendations by the ESPGHAN are reached with a lower increase in osmolality.

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

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, ß2 -microglobulin, myoglobin, prolactin, α1 -microglobulin, free kappa and lambda immunoglobulin light chains (kFLC and λFLC), α1 -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 ß2 -microglobulin RR was higher in pre-HDF and post-HDF. Myoglobin and prolactin RRs were higher with HDx and post-HDF. The α1 -microglobulin and α1 -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 kFLC 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.

Evaluation of the influence of the surface membrane and blood flow in medium «cut-off¼ (MCO) dialyzers. / Valoración de la influencia de la superficie de la membrana y el flujo sanguíneo en dializadores de medio cut-off.

INTRODUCTION: Recently, a new class of dialyzers, medium cut-off membranes (MCO), designed to improve the permeability, which could provide an efficacy similar to hemodiafiltration, have been incorporated into our therapeutic possibilities. To increase the knowledge about its use, the objective of the study was to evaluate the effect of the surface and blood flow (Qb) on the depurative efficacy in the MCO membranes. MATERIAL AND METHODS: We included 19 patients in the hemodialysis. Each patient received 6 sessions, in which the membrane surface was varied, from 1.7 to 2.0 m2, and/or the Qb (300, 350, 400 or 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 ß2-microglobulin, myoglobin, prolactin, α1-microglobulin and α1-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 m2 in the MCO dialyzer has not meant a greater depurative effectiveness. In these dialyzers the increase of Qb does not seem to be as determinant as in hemodiafiltration except for the clearance of small molecules.

Filling the gap between lab and clinical impact: An open randomized diagnostic trial comparing urinary ethylglucuronide and ethanol in alcohol dependent outpatients.

BACKGROUND: Efforts aimed at reducing alcohol-related harm include early detection of risky drinkers as well as detection of early relapse in patients with alcohol dependence. Ethyl glucuronide (EtG) has been proven to be a reliable biomarker for the detection of recent drinking; however, no randomized, diagnostic trial to date has tested its impact on drinking outcomes. The aim of this study was to assess, in a randomized design, the implications of EtG screening on alcohol outcomes, compared to screening with a low sensitivity biomarker such as ethanol. METHODS: Alcohol dependent outpatients were randomized to either 24 weeks of continuous screening with EtG or ethanol. Patients were aware of screening methods and results. After 24 weeks, all participants were screened with EtG. Self-reports were also gathered. A logistic regression compared the rate of EtG positive results at study end between groups. Generalized estimating equations evaluated the descending monthly rate of EtG positive patients in the EtG group. RESULTS: A total of 162 patients were randomized. During the study period, the ethanol group showed less patients with positive screens (19/64 (29.7%) vs 58/98 (59%)). After 24 weeks, the EtG group showed a greater number of patients having a negative screening test compared to ethanol subjects when they were all screened with EtG (5/62 (8.1%) vs 13/39 (33.3%)). A significant decrease in the rate of EtG positive patients was found for the first three months of the study. CONCLUSIONS: Routine screening with EtG seems to reduce drinking and improve abstinence rates in alcohol dependent outpatients.

Evaluation of the dialyser inner diameter in online haemodiafiltration. / Valoración del diámetro interno del dializador en hemodiafiltración on-line.

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; ß2-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 α1-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.