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      Citrate versus Acetate-Based Dialysate in On-Line Haemodiafiltration. A Prospective Cross-Over Study

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          Abstract

          Background and Aims: A bicarbonate dialysate acidified with citrate (CD) has been reported to have local anticoagulant effect and improves biocompatibility. This study examines the effect of CD on dialysis efficiency, coagulation, acid-base status, electrolytes, and inflammation in patients in on-line hemodiafiltration (OL-HDF). Methods: 35 patients in OL-HDF were enrolled in a prospective, cross-over study for a 24-week period and two phases alternating CD and acetate dialysate fluid (AD). Parameters on study were predialysis levels of bicarbonate and ionic calcium, reactive C Protein (CRP), and beta-2 microglobulin (B2MG) and postdialysis levels of activated tromboplastine time, bicarbonate, and ionized calcium. Results: No significant differences in coagulation parameters, pH, and predialysis bicarbonate were found. The postdialysis bicarbonate and postdialysis calcium were lower with CD. Dialysis efficiency was greater with CD. Regarding inflammatory parameters, both CRP and B2MG were lower using CD. Conclusion: The use of CD is safe and effective in OL-HDF, and it improves dialysis efficacy, postdialysis alkalosis, and inflammation.

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          Most cited references 23

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          Citrate anticoagulation abolishes degranulation of polymorphonuclear cells and platelets and reduces oxidative stress during haemodialysis.

          During haemodialysis (HD), polymorphonuclear cells (PMNs) and platelets are activated and release various granule products, including myeloperoxidase (MPO) and platelet factor 4 (PF4). MPO triggers the generation of reactive oxygen species, leading to irreversible protein, carbohydrate and lipid modification. PF4 probably also contributes to oxidative stress. As previously shown, HD-induced PMN degranulation is almost completely abolished during citrate anticoagulation, most probably due to its calcium chelation ability. In the present study, apart from HD-induced PMN and platelet degranulation, oxidative stress was analysed during three modes of anticoagulation. Heparin, dalteparin and citrate (HDhep, HDdal and HDcit) were compared in a randomized, crossover fashion in eight chronic HD patients. Multiple blood samples were taken during the third HD session of each modality, from both the afferent and efferent line. Besides the degranulation markers MPO and PF4, various markers of oxidative stress were measured, including oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) and carboxymethyllysine (CML). During HDhep and HDdal, marked degranulation was observed shortly after the start of HD. In contrast, during HDcit, PF4 and MPO levels remained unaltered, suggesting no release at all. After 1 week of HDcit, ox-LDL levels were markedly reduced [median 26% (3-65%), P=0.01], if compared with HDhep and HDdal. As regards MDA and CML, no differences were found. This study shows first, that HD-induced PMN and platelet degranulation are early, most probably calcium-dependent processes and, secondly, that the formation of ox-LDL is clearly dependent on the type of anticoagulant applied.
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            On-line hemodiafiltration reduces the proinflammatory CD14+CD16+ monocyte-derived dendritic cells: A prospective, crossover study.

            It is not known whether high convective transport may have a role in modulating the chronic inflammation of hemodialysis (HD) patients. The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on proinflammatory peripheral monocytes: Percentage of CD14+CD16+ cells and their telomere length and spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6). In a prospective, crossover study, 31 patients who were on high-flux HD (HF-HD) were evaluated. Patients underwent the following sequence of treatments (4 mo each): HF-HD (basal), OL-HDF (period 1), HF-HD (period 2), OL-HDF (period 3), and HF-HD (period 4). The dialysis characteristics were similar in the two modalities; the only difference was a higher convective transport in the OL-HDF than in the HF-HD. All patients who were on OL-HDF periods showed a significantly lower number of CD14+CD16+ cells than on HF-HD (18.5 +/- 2.3 basal versus 13.6 +/- 2.9 period 1 and 13.9 +/- 2.3 period 3; P = 0.001). By contrast, HF-HD restored the number of CD14+CD16+ cells to the basal values (19.2 +/- 2.8 and 18.6 +/- 1.4, periods 2 and 4, respectively; NS). During OL-HDF periods, the reduction of CD14+CD16+ was paralleled by a decreased number of short telomere cells. Spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6) was increased in HF-HD as compared with OL-HDF. In conclusion, these results demonstrate that as compared with HF-HD, OL-HDF markedly reduces the number of proinflammatory CD14+CD16+ cells and the production of TNF-alpha and IL-6. Future studies are needed to assess the possible therapeutic effect of convective transport on chronic inflammation that is associated with HD.
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              Low polymorphonuclear cell degranulation during citrate anticoagulation: a comparison between citrate and heparin dialysis.

              Haemodialysis (HD)-induced bio-incompatibility includes alterations in both cellular elements and humoral factors. As far as polymorphonuclear (PMN) cells are concerned, an increase in both adhesion and degranulation has been reported. However, whereas increased PMN adherence and aggregation is highly linked with early transient complement activation, degranulation seems a continuous process, independent from the formation of complement degradation products. In the process of cell activation, including PMN degranulation, divalent cations (Ca2+) appear to play a pivotal role. As regionally administering citrate creates an almost Ca(2+)-free environment within the dialyser, it is tempting to speculate that Ca2+ dependent phenomena of bio-incompatibility, originating within the dialyser, can be attenuated by substituting conventional heparin for citrate. Therefore, both anticoagulation modalities were compared in 10 stable patients, undergoing haemodialysis (HD) treatment with cellulose-triacetate membranes (CTA) only. Apart from the intracellular granule products myeloperoxidase (MPO) and lactoferrin (LF), the classical parameters of bio-incompatibility, peripheral blood neutropenia and complement activation, were measured. Analysis of MPO and LF gradients across the dialyser (concentration in efferent line-concentration in afferent line) suggested that degranulation is an early process, that occurs mainly within the extracorporeal circuit. Citrate abolished the release of MPO almost completely, whereas LF release was partially inhibited. Neither neutropenia, nor complement activation could be correlated with the occurrence of degranulation. HD-induced PMN degranulation seems largely independent from complement activation, but primarily reliant on Ca2+, at least in the case of CTA membranes.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2015
                May 2015
                10 March 2015
                : 39
                : 1-3
                : 181-187
                Affiliations
                Department of Nephrology, University Hospital Santa Lucia, Cartagena, Murcia, Spain
                Author notes
                *Manuel Molina Nuñez, Department of Nephrology, University Hospital Santa Lucia, C/Mezquita s/n, Paraje Los Arcos, ES-30202 Cartagena, Murcia (Spain), E-Mail manuel.molina4@carm.es
                Article
                371569 Blood Purif 2015;39:181-187
                10.1159/000371569
                25791278
                © 2015 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 4, References: 32, Pages: 7
                Categories
                Original Paper

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