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      Detoxifying Capacity and Kinetics of Prometheus ® – A New Extracorporeal System for the Treatment of Liver Failure

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          Abstract

          Background/Aims: Extracorporeal liver support therapies have been used for several decades as a bridging therapy prior to liver transplantation or as an addendum to standard medical therapy. The Prometheus<sup>®</sup> system represents a cell-free, extracorporeal, liver assist method for the removal of both albumin-bound and water-soluble endogenous toxins. The aim of the present study was to evaluate the removal capacity and selectivity of the different inbuilt dialyzers and adsorption columns during a single 6-hour treatment. Methods: Nine patients with acute on chronic liver failure were included (6 females, age 49 ± 4 years). Levels of endogenous toxins (urea nitrogen [UN, mg/dl], creatinine [Cr, mg/dl], total bilirubin [tB, mg/dl], and bile acids [BA, µmol/l]) and albumin [Alb, g/l] were monitored in blood sampled at different sites (arterial line, venous line and between the absorbers and the high-flux dialyzer) and at various time points (time 0, 30, 60, 120, 240, and 360 min). Results: A significant decrease of the serum level of all toxins was observed (UN 108.7 ± 23.2 vs. 38.1 ± 14.9, Cr 2.4 ± 0.7 vs. 1.2 ± 0.3, tB 31.1 ± 4.1 vs. 17.0 ± 1.6, BA 155.7 ± 32.5 vs. 66.0 ± 15.4; mean ± SEM, time 0 vs. time 360, signed rank rest, all p < 0.005). The reduction rate of UN, Cr, tB and BA amounted to 68.1 ± 5.1, 45.9 ± 6.2, 41.2 ± 5.1, and 58.2 ± 5.0%, respectively. Blood clearances [Cl, ml/min] of all, but especially of the protein-bound toxins declined over time (Cl UN 171.5 ± 4.3 vs. 142.9 ± 16.8; Cl Cr 135.7 ± 10.0 vs. 111.8 ± 9.1; Cl tB 29.3 ± 5.1 vs. 13.7 ± 3.7; Cl BA 84.9 ± 4.8 vs. 45.1 ± 13.3; time 30 vs. time 360; linear mixed models, all p < 0.005). Serum albumin levels decreased by 2.9 ± 0.9 g/l (signed rank test, p = 0.055). Not unexpectedly, tB was almost uniquely cleared by the adsorbers (UN 0.2 ± 1.1, Cr 6.9 ± 5.7, tB 92.3 ± 4.2, BA 62.9 ± 3.9% of total Cl). Conclusion: Both albumin-bound and water-soluble toxins are adequately removed by the Prometheus<sup>®</sup> system. Our data suggest that the rate and efficacy of removal of albumin-bound toxins is related to both the strength of the albumin binding and the saturation of the adsorption columns. Limited losses of albumin occur during treatment with the Prometheus system.

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          Most cited references 15

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          Improvement of hepatorenal syndrome with extracorporeal albumin dialysis mars: Results of a prospective, randomized, controlled clinical trial

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            Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support.

            The use of xenogenic or genetically engineered cell types in bioartificial liver support systems requires separation methods between the patients' blood and the liver support bioreactors that guarantee the sufficient transfer of pathophysiologically relevant substances but prevent complications. The present paper describes a new membrane separation system that is nearly impermeable to proteins but enables the exchange of water soluble and protein bound toxins by a special membrane and a recycled protein containing dialysate. Because the full range of toxins in hepatic failure has still not been identified, the value of this membrane separation method was evaluated clinically. Thirteen patients suffering from life threatening hepatic failure who had not responded to state of the art therapy were treated with this device, the molecular adsorbent recycling system (MARS). The overall survival rate was 69%. All patients showed positive response to the therapy, indicating that the presented membrane separator combines therapeutic effectivity with the highest safety criteria for the patient by cutting the exchange of substances below the level of proteins.
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              Prometheus® – a new extracorporeal system for the treatment of liver failure☆

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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
                2005
                August 2005
                25 August 2005
                : 23
                : 5
                : 349-358
                Affiliations
                Department of Medicine, Divisions of aNephrology, bHepatology, and cMedical Intensive Care, University Hospital Leuven, Leuven, Belgium
                Article
                86885 Blood Purif 2005;23:349–358
                10.1159/000086885
                16020951
                © 2005 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: 5, Tables: 6, References: 21, Pages: 10
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/86885
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Adsorption, Dialysis, Liver failure, Albumin-bound toxins

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