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      Comparative accuracy of biomarkers for the prediction of hospital-acquired acute kidney injury: a systematic review and meta-analysis

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          Abstract

          Background

          Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI.

          Methods

          In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence.

          Results

          We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1–25.9), urinary NGAL (DOR 13.8, 95% CI 10.2–18.8), and serum NGAL (DOR 12.6, 95% CI 9.3–17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively.

          Conclusions

          Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients.

          Trial registration CRD42020207883, October 06, 2020.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13054-022-04223-6.

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          Most cited references155

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          Measuring inconsistency in meta-analyses.

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            The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

            Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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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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                Author and article information

                Contributors
                q91421028@ntu.edu.tw
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                12 November 2022
                12 November 2022
                2022
                : 26
                : 349
                Affiliations
                [1 ]GRID grid.19188.39, ISNI 0000 0004 0546 0241, Graduate Institute of Clinical Medicine, College of Medicine, , National Taiwan University, ; Taipei, Taiwan
                [2 ]GRID grid.454209.e, ISNI 0000 0004 0639 2551, Division of Nephrology, Department of Internal Medicine, , Keelung Chang Gung Memorial Hospital, ; Keelung, Taiwan
                [3 ]GRID grid.145695.a, ISNI 0000 0004 1798 0922, Chang Gung University College of Medicine, ; Taoyuan, Taiwan
                [4 ]GRID grid.454209.e, ISNI 0000 0004 0639 2551, Community Medicine Research Center, , Keelung Chang Gung Memorial Hospital, ; Keelung, Taiwan
                [5 ]GRID grid.412094.a, ISNI 0000 0004 0572 7815, Division of Nephrology, Department of Internal Medicine, , National Taiwan University Hospital, ; Room 1419, Clinical Research Building, 7 Chung-Shan South Road, Taipei, 100 Taiwan
                [6 ]GRID grid.412094.a, ISNI 0000 0004 0572 7815, NSARF (National Taiwan University Hospital Study Group of ARF) and CAKS (Taiwan Consortium for Acute Kidney Injury and Renal Diseases), ; Taipei, Taiwan
                [7 ]GRID grid.459908.9, Division of Nephrology, Department of Internal Medicine, , Camillian Saint Mary’s Hospital Luodong, ; Yilan, Taiwan
                [8 ]Saint Mary’s Junior College of Medicine, Nursing and Management, Yilan, 26546 Taiwan
                [9 ]GRID grid.481324.8, ISNI 0000 0004 0404 6823, Division of Nephrology, Taipei Tzu Chi Hospital, , Buddhist Tzu Chi Medical Foundation, ; New Taipei City, Taiwan
                [10 ]GRID grid.410764.0, ISNI 0000 0004 0573 0731, Department of Critical Care Medicine, , Taichung Veterans General Hospital, ; Taichung, Taiwan
                [11 ]GRID grid.410764.0, ISNI 0000 0004 0573 0731, Division of Nephrology, Department of Internal Medicine, , Taichung Veterans General Hospital, ; Taichung, Taiwan
                [12 ]GRID grid.413876.f, ISNI 0000 0004 0572 9255, Division of Nephrology, Department of Internal Medicine, , Chi Mei Medical Center, ; Tainan, Taiwan
                [13 ]Department of Health and Nutrition, ChiaNai University of Pharmacy and Science, Tainan, Taiwan
                [14 ]GRID grid.412896.0, ISNI 0000 0000 9337 0481, Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, , Taipei Medical University, ; Taipei, Taiwan
                [15 ]GRID grid.38142.3c, ISNI 000000041936754X, Harvard T.H. Chan School of Public Health, ; Boston, MA USA
                [16 ]Everan Hospital, Taichung, Taiwan
                [17 ]GRID grid.411508.9, ISNI 0000 0004 0572 9415, China Medical University Hospital, ; Taichung, Taiwan
                [18 ]GRID grid.415007.7, ISNI 0000 0004 0477 6869, Department of Internal Medicine, , Kaohsiung Municipal Ta-Tung Hospital, ; Kaohsiung, Taiwan
                [19 ]GRID grid.412027.2, ISNI 0000 0004 0620 9374, Division of Nephrology, Department of Internal Medicine, , Kaohsiung Medical University Hospital, ; Kaohsiung, Taiwan
                [20 ]GRID grid.454211.7, ISNI 0000 0004 1756 999X, Division of Nephrology, Department of Internal Medicine, , Linkou Chang Gung Memorial Hospital, ; Taoyuan, Taiwan
                [21 ]GRID grid.260539.b, ISNI 0000 0001 2059 7017, Institute of Public Health, , National Yang Ming Chiao Tung University, ; Taipei, Taiwan
                Article
                4223
                10.1186/s13054-022-04223-6
                9652605
                36371256
                c8ebd21d-2b25-4c31-887a-181f05e61b04
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 29 June 2022
                : 28 October 2022
                Funding
                Funded by: Ministry of Science and Technology (MOST) of the Republic of China (Taiwan)
                Award ID: MOST 108-2321-B-182-003
                Award ID: MOST 109-2321-B-182-001
                Award ID: MOST 106-2321-B-182-002
                Award ID: MOST 107-2321-B-182-004
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001868, National Science Council;
                Award ID: 104-2314-B-002-125-MY3
                Award ID: 106-2314-B-002 -166 -MY3
                Award ID: 107-2314-B-002-026-MY3
                Award Recipient :
                Funded by: National Health Research Institutes
                Award ID: PH-102-SP-09
                Award Recipient :
                Funded by: National Taiwan University Hospital
                Award ID: 106-FTN20
                Award ID: 106-P02
                Award ID: UN106-014
                Award ID: 106-S3582
                Award ID: 107-S3809
                Award ID: 107-T02
                Award ID: PC1246
                Award ID: VN109-09
                Award ID: 109-S4634
                Award ID: UN109-041
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Emergency medicine & Trauma
                acute kidney injury,biomarker,critically ill patient,neutrophil gelatinase-associated lipocalin

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