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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Accuracy of Anti-GBM Antibodies in Diagnosing Anti-Glomerular Basement Membrane Disease: A Systematic Review and Meta-Analysis

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          Abstract

          Background: The sensitivity and specificity of anti-glomerular basement membrane (GBM) antibodies have not been systematically analyzed. In this systematic review, we aimed to evaluate the diagnostic accuracy of anti-GBM antibodies for anti-GBM disease. Summary: Potential studies were searched using MEDLINE, Embase, the Cochrane Library, and the International Clinical Trials Registry Platform based on the index test and target condition. The inclusion criteria were prospective or retrospective cohort studies or case-control studies assessing the sensitivity and specificity of anti-GBM antibodies, and the reference standard was clinical diagnosis including biopsy results. The exclusion criteria were review articles, case reports, animal studies, and in vitro studies. Quality assessment was conducted based on the Quality Assessment of Diagnostic Accuracy Studies-2. The pooled estimates of sensitivity and specificity were calculated using a bivariate random-effects model. The overall quality was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation. Six studies (1,691 patients) and 11 index tests were included in our systematic review. A high risk of bias and concerns regarding the applicability of patient selection were noted because of the case-control design in 67% of the included studies. The pooled sensitivity and specificity were 93% (95% CI: 84–97%) and 97% (95% CI: 94–99%), respectively. The certainty of evidence was low because of the high risk of bias and indirectness. Key Messages: Anti-GBM antibodies may exhibit high sensitivity and specificity in the diagnosis of anti-GBM disease. Further cohort studies are needed to confirm their precise diagnostic accuracy and compare diagnostic accuracies among different immunoassays.

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          Most cited references36

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          QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.

          In 2003, the QUADAS tool for systematic reviews of diagnostic accuracy studies was developed. Experience, anecdotal reports, and feedback suggested areas for improvement; therefore, QUADAS-2 was developed. This tool comprises 4 domains: patient selection, index test, reference standard, and flow and timing. Each domain is assessed in terms of risk of bias, and the first 3 domains are also assessed in terms of concerns regarding applicability. Signalling questions are included to help judge risk of bias. The QUADAS-2 tool is applied in 4 phases: summarize the review question, tailor the tool and produce review-specific guidance, construct a flow diagram for the primary study, and judge bias and applicability. This tool will allow for more transparent rating of bias and applicability of primary diagnostic accuracy studies.
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            Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies

            Systematic reviews of diagnostic test accuracy synthesize data from primary diagnostic studies that have evaluated the accuracy of 1 or more index tests against a reference standard, provide estimates of test performance, allow comparisons of the accuracy of different tests, and facilitate the identification of sources of variability in test accuracy.
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              Diagnosis and classification of Goodpasture's disease (anti-GBM).

              Goodpasture's disease or anti-glomerular basement membrane disease (anti-GBM-disease) is included among immune complex small vessel vasculitides. The definition of anti-GBM disease is a vasculitis affecting glomerular capillaries, pulmonary capillaries, or both, with GBM deposition of anti-GBM autoantibodies. The disease is a prototype of autoimmune disease, where the patients develop autoantibodies that bind to the basement membranes and activate the classical pathway of the complement system, which start a neutrophil dependent inflammation. The diagnosis of anti-GBM disease relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis. Overt clinical symptoms are most prominent in the glomeruli where the inflammation usually results in a severe rapidly progressive glomerulonephritis. Despite modern treatment less than one third of the patients survive with a preserved kidney function after 6 months follow-up. Frequencies vary from 0.5 to 1 cases per million inhabitants per year and there is a strong genetic linkage to HLA-DRB1(∗)1501 and DRB1(∗)1502. Essentially, anti-GBM disease is now a preferred term for what was earlier called Goodpasture's syndrome or Goodpasture's disease; anti-GBM disease is now classified as small vessel vasculitis caused by in situ immune complex formation; the diagnosis relies on the detection of anti-GBM in tissues or circulation in conjunction with alveolar or glomerular disease; therapy is effective only when detected at an early stage, making a high degree of awareness necessary to find these rare cases; 20-35% have anti-GBM and MPO-ANCA simultaneously, which necessitates testing for anti-GBM whenever acute test for ANCA is ordered in patients with renal disease.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2021
                September 2021
                19 August 2021
                : 52
                : 7
                : 531-538
                Affiliations
                [_a] aDepartment of Respiratory Medicine, Ichinomiyanishi Hospital, Ichinomiya, Japan
                [_b] bSystematic Review Workshop Peer Support Group (SRWS-PSG), Osaka, Japan
                [_c] cDivision of Nephrology and Endocrinology, the University of Tokyo Graduate School of Medicine, Tokyo, Japan
                [_d] dDepartment of Rheumatology, Ichinomiyanishi Hospital, Ichinomiya, Japan
                [_e] eDepartment of Rheumatology, Teikyo University Chiba Medical Center, Chiba, Japan
                [_f] fDepartment of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
                [_g] gDepartment of Hospital Care Research Unit, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
                Author information
                https://orcid.org/0000-0003-0262-459X
                https://orcid.org/0000-0003-3053-5682
                Article
                518362 Am J Nephrol 2021;52:531–538
                10.1159/000518362
                34515033
                f13df4a5-cad7-47fe-aed9-25d4a487917c
                © 2021 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.

                History
                : 12 April 2021
                : 06 July 2021
                Page count
                Figures: 3, Tables: 3, Pages: 8
                Categories
                In-Depth Topic Review

                Cardiovascular Medicine,Nephrology
                Anti-glomerular basement membrane disease,Autoantibody,Diagnostic accuracy,Systematic review,Meta-analysis

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