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      Membrane Biocompatibility Does Not Affect Whole Body Protein Metabolism during Dialysis

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          Background: Protein-calorie malnutrition is present in 30–50% of dialysis patients. The lack of biocompatibility of the dialysis membrane, which results in low-grade inflammation, could be responsible for this malnutrition. We investigated whether protein-energy malnutrition could be partly due to incompatibility of the dialyzer during the dialysis session. Methods: Five patients were dialyzed during 2 periods of 3 weeks (cross-over) with either a single-use low-flux polysulfone or cellulose triacetate (biocompatible) or a single-use cuprophan (bio-incompatible) membrane. As a measure of whole body protein metabolism, a primed constant infusion of L-[1-<sup>13</sup>C]-valine was used during a 4-hour dialysis session. Results: Cuprophan was a more powerful activator of the complement system than other membranes. Protein metabolism parameters during both study protocols were not different and resulted in the same protein balance during polysulfone/cellulose triacetate (–15 ± 3) and cuprophan (–13 ± 2 µmol/kg/h) dialysis. Conclusion: In stable hemodialysis patients with no apparent complications, protein metabolism during dialysis is not affected by the compatibility of the dialysis membrane.

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          Most cited references 12

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          Amino acid and albumin losses during hemodialysis.

          Protein and calorie malnutrition are prevalent in chronic hemodialysis (HD) patients and has been linked to increased mortality and morbidity in this patient population. Concern has been raised that the open pore structure of high flux membranes may induce the loss of more amino acids (AA) compared to low flux membranes. To address this issue, we prospectively analyzed pre- and post-HD plasma AA profiles with three different membranes in nine patients. Simultaneously, we measured dialysate AA losses during HD. The membranes studied were: cellulosic (cuprophane-CU), low flux polymethylmethacrylate (LF-PMMA), and high flux polysulfone (HF-PS) during their first use. Our results show that pre-HD plasma AA profiles were abnormal compared to controls and decreased significantly during HD with all dialyzers. The use of HF-PS membranes resulted in significantly more AA losses into the dialysate when compared to LF-PMMA membranes (mean +/- SD; 8.0 +/- 2.8 g/dialysis for HF-PS, 6.1 +/- 1.5 g/dialysis for LF-PMMA, p < 0.05, and 7.2 +/- 2.6 g/dialysis for CU membranes, P = NS). When adjusted for surface area and blood flow, AA losses were not different between any of the dialyzers. We also measured dialysate AA losses during the sixth reuse of the HF-PS membrane. Losses of total AA increased by 50% during the sixth reuse of HF-PS membrane compared to its first use. In addition, albumin was detected in the dialysate during the sixth reuse of HF-PS membrane. We therefore measured albumin losses in all patients dialyzed with HF-PS membranes as a function of reuse.(ABSTRACT TRUNCATED AT 250 WORDS)
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            Effect of the membrane biocompatibility on nutritional parameters in chronic hemodialysis patients.

            Malnutrition is highly prevalent in chronic hemodialysis patients and is an important determinant of their morbidity and mortality. Several recent studies have suggested that the inflammatory response associated with the biocompatibility of the dialysis membranes is a potential contributing factor. In a prospective study of 159 new hemodialysis patients from two centers randomized to either a low-flux biocompatible (BCM) membrane or a low-flux bioincompatible (BICM) membrane, we measured the long-term effects of biocompatibility on several nutritional parameters, including estimated dry weight, serum albumin, insulin-like growth factor-1 (IGF-1), and prealbumin over 18 months. Our results show that the BCM group had a mean (+/- SD) increase in their dry weight of 2.96 +/- 6.88 kg at month 12 and 4.36 +/- 8.57 kg at month 18 (P < 0.05 vs. baseline for both), whereas no change in mean weight was observed in BICM group. Following initiation of hemodialysis, a significant increase was observed in serum albumin levels in both groups of patients. However, the biocompatible group had an earlier and more marked increase in serum albumin levels compared to the BICM group. The average increase in serum albumin compared to baseline was consistently greater than 0.25 g/dl after seven months in the BCM group, but did not reach this level until 12 months after initiation of dialysis in the BICM group. The difference between the groups was statistically significant at months 7, 8, and 10 (P < 0.05, higher in the BCM group). Furthermore, the overall difference in serum albumin concentration between the two groups was larger in the center where the dose of dialysis was equivalent (P < 0.001). A consistently higher value was also observed in IGF-1 levels for BCM patients compared to BICM group (P = NS). In a further analysis, changes in IGF-1 levels, but not prealbumin, predicted the subsequent changes in serum albumin. We conclude that biocompatible hemodialysis membranes favorably impact on the nutritional status of chronic hemodialysis patients, independently of the flux characteristics of the membranes, and that IGF-1 may be an early marker of nutritional status.
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              Relationship of plasma leucine and alpha-ketoisocaproate during a L-[1-13C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment.

              The keto analog of leucine, alpha-ketoisocaproate (KIC), is formed intracellularly from leucine and is released, in part, into the systemic circulation. Therefore. KIC can be used to estimate intracellular leucine tracer enrichment in man during labeled-leucine tracer experiments without requiring tissue biopsy samples. This approach was studied in young, healthy, male adults maintained on different dietary protein intakes from generous (1.5 g kg-1d-1) to deficient (0.0 g kg-1d-1) for 5-7 day periods. At the end of each dietary period, the volunteers were given a primed, continuous infusion of L-[1-13C]leucine either after an overnight fast (postabsorptive state) or while being fed hourly aliquots of the same diet. The plasma concentrations of all 3 branched-chain amino and keto acid pairs were measured from early morning blood samples taken from 4 subjects at 4 different levels of protein intake. Leucine concentration showed a weak correlation, and valine concentration showed a strong correlation with protein intake; isoleucine and the 3 keto acids did not. However, each branched-chain amino acid concentration was strongly correlated with its corresponding keto acid concentration. In plasma samples obtained during the L-[1-13C]leucine infusions, the ratio of [1-13C]KIC to [1-13C]leucine enrichment ratio remained relatively constant (77 +/- 1% over the wide range of dietary protein intakes and for both the fed and postabsorptive states. For the tissues from which the plasma KIC originates, the rate of plasma leucine into cells will account for approximately 77% of the intracellular leucine flux with the remaining 23% coming primarily from leucine release via protein breakdown. The constant nature of the plasma KIC to leucine 13C enrichment ratio implies that relative changes in leucine kinetics will appear the same under many dietary circumstances regardless of whether plasma leucine or KIC enrichments are used for the calculations.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                May 2005
                19 May 2005
                : 23
                : 3
                : 211-218
                aDepartment of Internal Medicine, Division of Nephrology, bDepartment of Pediatrics, University Hospital Groningen, and cGroningen University Institute of Drug Exploration, GUIDE, Groningen, The Netherlands
                84891 Blood Purif 2005;23:211–218
                © 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: 4, References: 21, Pages: 8
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/84891
                Original Paper

                Cardiovascular Medicine, Nephrology

                Protein turnover, Amino acid, Valine, Stable isotope, Hemodialysis


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