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      Serum β2-Microglobulin Correlates Positively with Left Ventricular Hypertrophy in Long-Term Hemodialysis Patients

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          Abstract

          Background/Aims: β<sub>2</sub>-Microglobulin (β<sub>2</sub>-MG) is a major protein component of dialysis-related amyloidosis. In long-term hemodialysis (HD) patients, β<sub>2</sub>-MG amyloid deposits not only in osteoarticular tissues, but also in systemic tissues, including the heart. The purpose of this study was to investigate the relationship between serum β<sub>2</sub>-MG concentrations and echocardiographic parameters in long-term HD patients in a cross-sectional study. Methods: Measurement of serum β<sub>2</sub>-MG concentrations and echocardiography were performed in 251 patients who had undergone HD therapy for more than 10 years. Results: The left ventricular mass index (LVMI) of the higher serum β<sub>2</sub>-MG (≥30 mg/l) group was significantly higher than that of the lower serum β<sub>2</sub>-MG (<30 mg/l) group (151.5 ± 45.7 vs. 137.0 ± 44.5 g/m<sup>2</sup>, p = 0.020). In simple regression analyses, serum β<sub>2</sub>-MG concentrations correlated significantly and positively with interventricular septum thickness (IVST) (r = 0.215, p < 0.001), posterior left ventricular wall thickness (PWT) (r = 0.249, p < 0.001), left ventricular wall thickness (LVWT) (r = 0.252, p < 0.001), relative wall thickness (RWT) (r = 0.153, p = 0.015) and LVMI (r = 0.171, p = 0.007). Multiple regression analyses revealed that serum β<sub>2</sub>-MG concentrations correlated significantly and positively with IVST, PWT, LVWT and RWT. Conclusion: Serum β<sub>2</sub>-MG concentrations correlated significantly and positively with the echocardiographic parameters of left ventricular hypertrophy (LVH) in long-term HD patients. Thus, deposition of β<sub>2</sub>-MG amyloid in the heart may be associated with LVH progression.

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          Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.

          Richard Devereux, Daniel R. Alonso, Elizabeth M. Lutas … (1986)
          To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society of Echocardiography (ASE) conventions and cube function and volume correction formulas in 52 patients. Penn-cube LV mass correlated closely with necropsy LV mass (r = 0.92, p less than 0.001) and overestimated it by only 6%; sensitivity in 18 patients with LV hypertrophy (necropsy LV mass more than 215 g) was 100% (18 of 18 patients) and specificity was 86% (29 of 34 patients). ASE-cube LV mass correlated similarly to necropsy LV mass (r = 0.90, p less than 0.001), but systematically overestimated it (by a mean of 25%); the overestimation could be corrected by the equation: LV mass = 0.80 (ASE-cube LV mass) + 0.6 g. Use of ASE measurements in the volume correction formula systematically underestimated necropsy LV mass (by a mean of 30%). In a subset of 9 patients, 3 of whom had technically inadequate M-mode echocardiograms, 2-dimensional echocardiographic (echo) LV mass by 2 methods was also significantly related to necropsy LV mass (r = 0.68, p less than 0.05 and r = 0.82, p less than 0.01). Among other indexes of LV anatomy, only measurement of myocardial cross-sectional area was acceptably accurate for quantitation of LV mass (r = 0.80, p less than 0.001) or diagnosis of LV hypertrophy (sensitivity = 72%, specificity = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)
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            Serum beta2-microglobulin level is a significant predictor of mortality in maintenance haemodialysis patients.

            Senji Okuno, K Kohno, Y Fujino … (2009)
            Beta(2)-microglobulin (beta(2)-M) is recognized as a surrogate marker of middle-molecule uraemic toxins and is a key component in the genesis of dialysis-associated amyloidosis. Few studies have evaluated the association of beta(2)-M levels with clinical outcome in dialyzed patients. The prognostic implication of serum beta(2)-M levels for the survival of haemodialysis patients was examined in 490 prevalent haemodialysis patients (60.1 +/- 11.8 years, haemodialysis duration of 87.4 +/- 75.7 months, 288 males and 202 females; 24% diabetics). The patients were divided into two groups according to their serum beta(2)-M levels: lower beta(2)-M group (n = 245) with serum beta(2)-M or=32.2 mg/L. During the follow-up period of 40 +/- 15 months, there were 91 all-cause deaths, and out of them, 36 were from cardiovascular diseases. Kaplan-Meier analysis revealed that all-cause mortality in the higher beta(2)-M group was significantly higher compared to that in the lower beta(2)-M group (P < 0.001). Multivariate Cox proportional hazards analyses showed that serum beta(2)-M level was a significant predictor for all-cause mortality (hazard ratio, 1.05; 95% CI, 1.01-1.08; P = 0.005), and for non-cardiovascular mortality (hazard ratio, 1.06; 95% CI, 1.02-1.10; P = 0.006), after adjustment for age, gender, haemodialysis duration, the presence of diabetes, serum albumin and serum C-reactive protein. These results demonstrate that the serum beta(2)-M level is a significant predictor of mortality in haemodialysis patients, independent of haemodialysis duration, diabetes, malnutrition and chronic inflammation, suggesting the clinical importance of lowering serum beta(2)-M in these patients.
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              Beta2-microglobulin.

              Tilman B. Drueke, Ziad Massy (2015)
              Among the uremic toxins in the "middle molecule" range, beta2-microglobulin (beta2-M) is certainly one of the most frequently studied compounds. Its serum level increases with the progression of chronic kidney disease, to reach very high concentrations in patients with end-stage kidney disease. It is the major protein component of dialysis-related amyloidosis, a dramatic complication which results from high extracellular concentration and posttranslational modification of beta2-M and a number of other promoters of amyloid fibril formation and deposition in osteo-articular tissues. Effective removal of beta2-M can be achieved with highly effective hemodialysis and hemodiafiltration techniques but predialysis session serum levels cannot be normalized. The prevalence and severity of beta2-M amyloidosis appear to have decreased in the last 20 years, although its occurrence may simply be delayed.
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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2014
                Publication date (Print): December 2014
                Publication date (Electronic): 04 November 2014
                Volume: 128
                Issue: 1-2
                Pages: 101-106
                Affiliations
                aDepartment of Metabolism, Endocrinology, Molecular Medicine, and Nephrology, Osaka City University Graduate School of Medicine, and bShirasagi Hospital, Osaka, and cInoue Hospital, Suita, Japan
                Author notes
                *Eiji Ishimura, MD, PhD, Department of Nephrology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan), E-Mail ish@med.osaka-cu.ac.jp
                Article
                Publisher ID: 365447 Other ID: Nephron Clin Pract 2014;128:101-106
                DOI: 10.1159/000365447
                PubMed ID: 25376242
                SO-VID: a84e400b-e8a3-4a2e-8fc6-57d1b3cfc3df
                Copyright © © 2014 S. Karger AG, Basel
                License:

                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.

                History
                Date received : 19 February 2014
                Date accepted : 24 June 2014
                Page count
                Figures: 3, Tables: 3, Pages: 6
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: β2-Microglobulin,Left ventricular hypertrophy,Left ventricular wall thickness,Long-term hemodialysis
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: β2-Microglobulin, Left ventricular hypertrophy, Left ventricular wall thickness, Long-term hemodialysis

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