In-Depth Topic Review Am J Nephrol 2021;52:531–538 Accuracy of Anti-GBM Antibodies in Diagnosing Anti-Glomerular Basement Membrane Disease: A Systematic Review and Meta-Analysis Akihiro Shiroshita a, b Yasuhiro Oda c Seiji Takenouchi d Noboru Hagino e Yuki Kataoka b, f, g a Department of Respiratory Medicine, Ichinomiyanishi Hospital, Ichinomiya, Japan; b Systematic Review Workshop Peer Support Group (SRWS-PSG), Osaka, Japan; c Division of Nephrology and Endocrinology, the University of Tokyo Graduate School of Medicine, Tokyo, Japan; d Department of Rheumatology, Ichinomiyanishi Hospital, Ichinomiya, Japan; e Department of Rheumatology, Teikyo University Chiba Medical Center, Chiba, Japan; f Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan; g Department of Hospital Care Research Unit, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan Received: April 12, 2021 Accepted: July 6, 2021 Published online: August 19, 2021 Correspondence to: Akihiro Shiroshita, akihirokun8 @gmail.com © 2021 S. Karger AG, Basel karger@karger.com www.karger.com/ajn DOI: 10.1159/000518362 Keywords Anti-glomerular basement membrane disease · Autoantibody · Diagnostic accuracy · Meta-analysis · Systematic review Abstract Background: The sensitivity and specificity of anti-glomeru- lar 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 an- ti-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 calculat- ed using a bivariate random-effects model. The overall qual- ity was evaluated using the Grades of Recommendation, As- sessment, 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 appli- cability 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 evi- dence was low because of the high risk of bias and indirect- ness. Key Messages: Anti-GBM antibodies may exhibit high sensitivity and specificity in the diagnosis of anti-GBM dis- ease. Further cohort studies are needed to confirm their pre- cise diagnostic accuracy and compare diagnostic accuracies among different immunoassays. © 2021 S. Karger AG, Basel Introduction Anti-glomerular basement membrane (GBM) disease is characterized by glomerulonephritis and pulmonary hemorrhage caused by anti-GBM antibodies or autoanti- bodies against the key epitope regions of the non-collage- nous domain 1 of the α3-chain of type IV collagen [1].