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      Analysis of β 2-Microglobulin Kinetics in Hemodialysis by a Modified Variable-Volume One-Compartment Model

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          Abstract

          It has been reported that deposition of β<sub>2</sub>-microglobulin (BMG) is associated with the occurrence of dialysis-related amyloidosis (DRA) in long-term hemodialysis (HD) patients. Though reduction of the BMG burden is essential in preventing DRA, simple BMG kinetic models applicable to clinical practice have not been established. We have reported a modified variable-volume one-compartment model (1CM) for analyzing urea nitrogen (UN) kinetics, in which no specific parameters other than a modification factor are necessary. If there is a constant relation between the BMG concentration of the dialyzer arterial line and the mean BMG concentration in the body during HD, the modified 1CM may also be applied to BMG. As such, in order to verify its validity, we analyzed UN and BMG kinetics by the modified 1CM in 28 HD patients in whom polysulfone dialyzers were used, and compared the calculated and measured solute rebound. In 3 of the patients, the spent dialysate was collected in a tank, and the BMG removal mass, calculated by the modified 1CM, was compared with that recovered in the tank. The BMG rebound ratio (%), calculated by the modified 1CM, was not different from the measured one (36.3 ± 9.9 vs. 36.5 ± 11.5, p = 0.954), as in the case of UN (15.8 ± 4.5 vs. 16.3 ± 4.6, p = 0.541). The solute dilution in the blood circuit by solute disequilibrium and blood recirculations for BMG was estimated to be 74% stronger than that for UN. The normalized solute generation rate (mg/min/l) and the time-averaged solute concentration over a 1-week period (mg/l) were 0.142 ± 0.023 and 448 ± 68 for UN and 0.00578 ± 0.00125 and 22.4 ± 4.6 for BMG, respectively. The differences between these two solutes resulted in a Dilution index for BMG that was 23% lower than that for UN (2.62 ± 0.44 vs. 3.21 ± 0.39, p < 0.0001). The modified 1CM overestimated the BMG removal mass (mg) by about 20% compared with that recovered in the tank (195 ± 22 vs. 162 ± 17, p < 0.0001). One of the causes of this discrepancy was speculated to be adsorption of BMG by polysulfone dialyzers. It was concluded that, despite several problems in quantitative analysis, the modified 1CM would be a useful model for estimating the dialysis efficiency for BMG removal in clinical practice.

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          Analysis of Urea Nitrogen and Creatinine Kinetics in Hemodialysis: Comparison of a Variable-Volume Two-Compartment Model with a Regional Blood Flow Model and Investigation of an Appropriate Solute Kinetics Model for Clinical Application

          To investigate an appropriate solute kinetics model for clinical application, we analyzed urea nitrogen (UN) and creatinine (Cr) kinetics by a variable-volume two-compartmental model (2CM) and a regional blood flow model (RBF) in 44 hemodialysis patients with varying proportions of first compartmental volume and regional volume (p 1 ). Solute kinetics could not be solved in some of the patients with higher p 1 values, and there were more solution failures by the RBF than by the 2CM. The solute generation rate (g) and solute distribution volume in the dry state (V D ) increased with increases in p 1 in both models, but there were some differences between the two models. When g was normalized by V D , it became relatively constant, irrespective of the p 1 value or model used (0.133 ± 0.029 mg/min/l by the 2CM and 0.132 ± 0.029 mg/min/l by the RBF for UN; 0.0200 ± 0.0049 mg/min/l by the 2CM and 0.0198 ± 0.0048 mg/min/l by the RBF for Cr). The intercompartmental mass transfer coefficient (K c ; liters/min) calculated by the 2CM decreased as p 1 increased (K c = –1.77·p 1 + 1.16, p c = –0.847·p 1 + 0.556, p sys ; liters/min) calculated by the RBF also decreased as p 1 increased (Q sys = –11.1·p 1 + 6.21, p sys = –5.22·p 1 + 2.90, p sys values for UN and Cr, the 2CM was considered to be a superior model. When p 1 was extremely low, the 2CM could be transformed into a modified variable-volume one-compartment model (1CM) which presented a similar g/V D (0.133 ± 0.029 for UN; 0.0200 ± 0.0048 for Cr). This modified 1CM was considered to satisfy appropriate conditions for clinical application, since it is simpler than the 2CM and provides useful information on the dialysis dose.
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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
            2001
            2001
            20 September 2001
            : 19
            : 4
            : 388-394
            Affiliations
            aShakai-Hoken Mishima Hospital, Mishima City, Shizuoka and bTokyo Medical and Dental University, Tokyo, Japan
            Article
            46969 Blood Purif 2001;19:388–394
            10.1159/000046969
            11574735
            © 2001 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: 4, Tables: 4, References: 24, Pages: 7
            Product
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/46969
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