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.

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

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

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.

Apixaban Downregulates Endothelial Inflammatory and Prothrombotic Phenotype in an In Vitro Model of Endothelial Dysfunction in Uremia.

PURPOSE: Chronic kidney disease (CKD) associates with inflammatory and prothrombotic phenotypes, resulting in higher cardiovascular risk. Factor Xa displays functions beyond coagulation, exhibiting proinflammatory effects. The aim of the present study was to investigate whether a direct FXa inhibitor protects from the endothelial dysfunction (ED) caused by uremia. METHODS: Macro (HUVEC) and microvascular (HMEC) endothelial cells (ECs) were exposed to serum from uremic patients or healthy donors, in absence and presence of apixaban (60 ng/ml). We evaluated changes in surface VCAM-1 and ICAM-1, intracellular eNOS, reactive oxygen species (ROS), and von Willebrand Factor (VWF) production by immunofluorescence, reactivity of the extracellular matrix (ECM) towards platelets, and intracellular signaling. RESULTS: ECs exposed to uremic serum triggered dysregulation of all the parameters. Presence of apixaban resulted in decreased expression of VCAM-1 (178 ± 14 to 89 ± 2% on HMEC and 324 ± 71 to 142 ± 25% on HUVEC) and ICAM-1 (388 ± 60 to 111 ± 10% on HMEC and 148 ± 9% to 90 ± 7% on HUVEC); increased eNOS (72 ± 8% to 95 ± 10% on HMEC); normalization of ROS levels (173 ± 21 to 114 ± 13% on HMEC and 165 ± 14 to 127 ± 7% on HUVEC); lower production of VWF (168 ± 14 to 92 ± 4% on HMEC and 151 ± 22 to 99 ± 11% on HUVEC); and decreased platelet adhesion onto ECM (134 ± 22 to 93 ± 23% on HMEC and 161 ± 14 to 117 ± 7% on HUVEC). Apixaban inhibited p38MAPK and p42/44 activation in HUVEC (139 ± 15 to 48 ± 15% and 411 ± 66 to 177 ± 57%, respectively) (p < 0.05 vs control for all parameters). CONCLUSION: Anti-FXa strategies, such as apixaban, prevented ED caused by the uremic milieu, exhibiting anti-inflammatory and antioxidant properties and modulating the reactivity of the ECM.

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

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

Efficacy and safety of the Clearum dialyzer.

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

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

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

Up-regulation of HDACs, a harbinger of uraemic endothelial dysfunction, is prevented by defibrotide.

Endothelial dysfunction is an earlier contributor to the development of atherosclerosis in chronic kidney disease (CKD), in which the role of epigenetic triggers cannot be ruled out. Endothelial protective strategies, such as defibrotide (DF), may be useful in this scenario. We evaluated changes induced by CKD on endothelial cell proteome and explored the effect of DF and the mechanisms involved. Human umbilical cord vein endothelial cells were exposed to sera from healthy donors (n = 20) and patients with end-stage renal disease on haemodialysis (n = 20). Differential protein expression was investigated by using a proteomic approach, Western blot and immunofluorescence. HDAC1 and HDAC2 overexpression was detected. Increased HDAC1 expression occurred at both cytoplasm and nucleus. These effects were dose-dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up-regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule-1, surface Toll-like receptor-4, von Willebrand Factor and reactive oxygen species. Moreover, DF down-regulated HDACs expression through the PI3/AKT signalling pathway. HDACs appear as key modulators of the CKD-induced endothelial dysfunction as specific blockade by trichostatin A or by DF prevents endothelial dysfunction responses to the CKD insult. Moreover, DF exerts its endothelial protective effect by inhibiting HDAC up-regulation likely through PI3K/AKT.

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

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

Study of Biocompatibility of Membranes in Online Hemodiafiltration.

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

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

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

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

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

Antioxidant and Anti-Inflammatory Strategies Based on the Potentiation of Glutathione Peroxidase Activity Prevent Endothelial Dysfunction in Chronic Kidney Disease.

BACKGROUND/AIMS: Accelerated atherosclerosis in chronic kidney disease (CKD) is preceded by endothelial dysfunction (ED), which exhibits a proinflammatory and prothrombotic phenotype and enhanced oxidative stress. In this study, the effect of several compounds with anti-inflammatory and/or antioxidant properties on uremia-induced endothelial dysfunction has been evaluated in an in vitro model. METHODS: Endothelial cells (ECs) were exposed to sera from uremic patients in the absence and presence of the flavonoids apigenin, genistein and quercetin, the antioxidant enzyme mimetics (AEM) ebselen (glutathione peroxidase mimetic), EUK-134 and EUK-118 (both superoxide dismutase mimetics), and the pharmacological drug N-acetylcysteine (NAC). We explored changes in the expression of adhesion receptors on the cell surface, by immunofluorescence, the production of radical oxygen species (ROS), by fluorescence detection, and the activation of signaling proteins related to inflammation, by both a phosphospecific antibody cell-based ELISA and immunoblotting techniques. RESULTS: Uremic media induced a significantly increased expression of ICAM-1, overproduction of radical oxygen species (ROS) and activation of p38 mitogen activated protein kinase (p38MAPK) and Nuclear Factor kB (NFkB) in ECs. Quercetin, the AEM and NAC showed a significant inhibitory effect on both ICAM-1 expression and ROS generation (p<0.05). All the compounds reduced p38MAPK activation, but only the AEM, especially ebselen, and NAC, both potentiating the glutathione peroxidase pathway, also inhibited NFkB activation. These two compounds were capable of increasing endothelial glutathione levels, especially in response to uremia. CONCLUSION: Our results indicate that the potentiation of the antioxidant pathways can be an effective strategy to improve endothelial dysfunction in uremia and a potential target to reduce the cardiovascular risk in this population.

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

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/m2 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/m2; 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.

TLR4 and NALP3 inflammasome in the development of endothelial dysfunction in uraemia.

BACKGROUND: The increased cardiovascular risk present in chronic kidney disease (CKD) is related to the development of endothelial dysfunction, whose mechanisms are still unclear. Accumulation of toxins and proinflammatory cytokines may constitute danger-associated molecular patterns (DAMP) to which endothelial cells are continuously exposed. Potential involvement of mechanisms recognizing DAMP, such as TLR and inflammasomes, has been explored. MATERIALS AND METHODS: Endothelial cells in culture were exposed to sera samples collected from patients with CKD: (i) stages 4-5 not on dialysis (PreD), (ii) on maintenance haemodialysis (HD) and (iii) peritoneal dialysis (PD). Changes in TLR4 and ICAM-1 expression, reactive oxygen species (ROS) production and TLR4 signalling were explored. Assembly of NALP3 inflammasome components was also investigated. RESULTS: TLR4 was expressed at the cell surface and increased significantly in response to PreD, HD and PD sera, paralleling with the activation of the cell stress protein Akt and the inflammation-related transcription factor NFκB, with elevated surface ICAM-1 expression and ROS production. TLR4 blockade partially decreased these effects. Exposure of cells to uraemic sera induced assembly of NALP3 components, with caspase-1 activation, especially in response to HD and PD sera. CONCLUSIONS: TLR4 and NALP3 inflammasomes, crucial elements of innate immunity, contribute to the development and perpetuation of endothelial dysfunction in response to the uraemic toxicity. These mechanisms constitute potential therapeutic targets to improve endothelial dysfunction and to reduce the increased cardiovascular risk in CKD.

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.

Correlation of plasmatic sodium determined by the laboratory and that determined by the dialysis machine.

INTRODUCTION: Changes in plasma sodium concentration (pNa, expressed in mEq/L) are common in hemodialysis (HD) patients. Hemodialysis monitors can estimate pNa by using an internal algorithm based on ion dialysance measurements. The present study studies the accuracy of the correlation between the pNa estimated by the dialysis monitor and that measured by the biochemistry laboratory at our center. MATERIAL AND METHODS: A single-centre prospective observational study in patients on a chronic HD program with the 6008 CAREsystem monitor and standard sodium (138mmol/L) and bicarbonate (32mmol/L) prescriptions. Venous blood samples were drawn from each patient before and after each HD session to ensure inter- and intra-individual validity. The pNa was measured in the biochemistry laboratory using indirect potentiometry and simultaneously the estimated pNa by the HD monitor was recorded at the beginning and at the end of the HD session. For statistical analysis, a scatterplot was made, and Spearman's correlation quotient was calculated. In addition, the differences between both methods were represented as Bland-Altman diagrams. RESULTS: The pre-dialysis pNa measured in the laboratory was 137.49±3.3, and that of the monitor, 137.96±2.91, with a correlation with R2 value of 0.683 (p<0.001). The post-dialysis pNa measured in the laboratory was 137.08±2.23, and that of the monitor was 138.87±1.88, with an R2 of 0.442 (p<0.001). On the Bland-Altman plots, the pre-dialysis pNa has a systematic error of 0.49, in favor of the monitor-estimated pNa, with a 95% confidence interval (CI) of (-3.24 to a 4.22). In the post-dialysis pNa, a systematic error of 1.79 with a 95% CI of (-1.64 to 5.22) was obtained. CONCLUSION: The correlation between the pNa estimated by Fresnius 6008 CAREsystem HD monitor and that measured by the laboratory is good, especially pre-dialysis measurements. Further studies should verify the external validity of these results.

Non-valvular atrial fibrillation in patients on peritoneal dialysis, prevalence, treatment and professionals involved.

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillars for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population. The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1,403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% or in consensus with the nephrologist 43%). In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scores used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.

Impact of Remote Monitoring on Standardized Outcomes in Nephrology-Peritoneal Dialysis.

Introduction: This study aimed to evaluate the association between the use of remote patient monitoring (RPM) in patients on automated peritoneal dialysis (APD) and the Standardized Outcomes in Nephrology in peritoneal dialysis (SONG-PD) clinical outcomes. Methods: A prospective and multicenter cohort study was conducted on patients with advanced chronic kidney disease on APD, recruited at 16 Spanish Hospitals, between June 1 and December 31, 2021. Patients were divided into 2 cohorts, namely patients on APD with RPM (APD-RPM) and patients on APD without RPM. The primary endpoints were the standardized outcomes of the SONG-PD clinical outcomes: PD-associated infection, cardiovascular disease (CVD), mortality rate, technique survival, and life participation (assessed as health-related quality of life [QoL]). Propensity score matching (PSM) was used to evaluate the association of RPM exposure with the clinical outcomes. Results: A total of 232 patients were included, 176 (75.9%) in the APD-RPM group and 56 (24.1%) in the APD-without-RPM group. The mean patient follow-up time was significantly longer in the APD-RPM group than in the APD-without-RPM group (10.4 ± 2.8 vs. 9.4 ± 3.1 months, respectively; P = 0.02). In the overall study sample, the APD-RPM group was associated with a lower mortality rate (hazard ratio [HR]: 0.08; 95% confidence interval [CI]: 0.01 to 0.69; P = 0.020) and greater technique survival rate (HR: 0.25; 95% CI: 0.11 to 0.59; P = 0.001). After PSM, APD-RPM continued to be associated with better technique survival (HR: 0.23; 95% CI: 0.06 to 0.83; P = 0.024). Conclusion: The use of RPM programs in patients on APD was associated with better survival of the technique and lower mortality rates. However, after PSM, only technique survival was significant.