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      Analysis of a Urinary Biomarker Panel for Clinical Outcomes Assessment in Cirrhosis

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          Abstract

          Background

          Biomarkers are potentially useful in assessment of outcomes in patients with cirrhosis, but information is very limited. Given the large number of biomarkers, adequate choice of which biomarker(s) to investigate first is important.

          Aim

          Analysis of potential usefulness of a panel of urinary biomarkers in outcome assessment in cirrhosis.

          Patients and Methods

          Fifty-five patients with acute decompensation of cirrhosis were studied: 39 had Acute Kidney Injury (AKI) (Prerenal 12, type-1 HRS (hepatorenal syndrome) 15 and Acute Tubular Necrosis (ATN) 12) and 16 acute decompensation without AKI. Thirty-four patients had Acute-on-chronic liver failure (ACLF). A panel of 12 urinary biomarkers was assessed, using a multiplex assay, for their relationship with ATN, ACLF and mortality.

          Results

          Biomarker with best accuracy for ATN diagnosis was NGAL (neutrophil-gelatinase associated lipocalin): 36 [26-125], 104 [58-208] and 1807 [494-3,716] μg/g creatinine in Prerenal-AKI, type-1 HRS and ATN, respectively; p<0.0001 (AUROC 0.957). Other attractive biomarkers for ATN diagnosis were IL-18, albumin, trefoil-factor-3 (TFF-3) and glutathione-S-transferase-π (GST-π) Biomarkers with less accuracy for ATN AUCROC<0.8 were β2-microglobulin, calbindin, cystatin-C, clusterin and KIM-1 (kidney injury molecule-1). For ACLF, the biomarker with the best accuracy was NGAL (ACLF vs. No-ACLF: 165 [67-676] and 32 [19-40] μg/g creatinine; respectively; p<0.0001; AUROC 0.878). Interestingly, other biomarkers with high accuracy for ACLF were osteopontin, albumin, and TFF-3. Biomarkers with best accuracy for prognosis were those associated with ACLF.

          Conclusions

          A number of biomarkers appear promising for differential diagnosis between ATN and other types of AKI. The most interesting biomarkers for ACLF and prognosis are NGAL, osteopontin, albumin, and TFF-3. These results support the role of major inflammatory reaction in the pathogenesis of ACLF.

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          Most cited references26

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          Renal failure in cirrhosis.

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            Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes

            Since its first description more than 20 years ago osteopontin has emerged as an active player in many physiological and pathological processes, including biomineralization, tissue remodeling and inflammation. As an extracellular matrix protein and proinflammatory cytokine osteopontin is thought to facilitate the recruitment of monocytes/macrophages and to mediate cytokine secretion in leukocytes. Modulation of immune cell response by osteopontin has been associated with various inflammatory diseases and may play a pivotal role in the development of adipose tissue inflammation and insulin resistance. Here we summarize recent findings on the role of osteopontin in metabolic disorders, particularly focusing on diabetes and obesity.
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              Current Use of Biomarkers in Acute Kidney Injury: Report and Summary of Recommendations from the 10th Acute Dialysis Quality Initiative Consensus Conference

              Over the last decade there has been considerable progress in the discovery and development of biomarkers of kidney disease, and several have now been evaluated in different clinical settings. While there is a growing literature on the performance of various biomarkers in clinical studies, there is limited information on how these biomarkers would be utilized by clinicians to manage patients with acute kidney injury (AKI). Recognizing this gap in knowledge, we convened the 10th Acute Dialysis Quality Initiative (ADQI) meeting to review the literature on biomarkers in AKI and their application in clinical practice. We asked an international group of experts to assess four broad areas for biomarker utilization for AKI: risk assessment, diagnosis and staging; differential diagnosis; prognosis and management and novel physiological techniques including imaging. This article provides a summary of the key findings and recommendations of the group, to equip clinicians to effectively use biomarkers in AKI.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 June 2015
                2015
                : 10
                : 6
                : e0128145
                Affiliations
                [1 ]Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain
                [2 ]Institut d’Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain
                [3 ]Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain
                [4 ]Instituto Reina Sofía de Investigación Nefrológica (IRSIN), Barcelona, Spain
                [5 ]Biochemistry and Molecular Genetics Department, Hospital Clínic, University of Barcelona, Barcelona, Catalunya, Spain
                University of Torino, ITALY
                Author notes

                Competing Interests: The authors have declared that they have no competing interests.

                Conceived and designed the experiments: PG XA ES RB. Performed the experiments: MMR WJ. Analyzed the data: PG XA CE ES RB. Contributed reagents/materials/analysis tools: MMR WJ. Wrote the paper: PG XA ES RB. Data collection: XA CE RB ER RM MMR PH CS. Critical revision of data and manuscript revision: PG VA JF IG XA RB ES WJ PH CS.

                Article
                PONE-D-15-05639
                10.1371/journal.pone.0128145
                4456079
                26042740
                08c8af57-aec7-4af9-be80-844c2efa8ca6
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 10 February 2015
                : 22 April 2015
                Page count
                Figures: 0, Tables: 9, Pages: 14
                Funding
                Part of the work reported in this study has been funded by the project PI08/0126 and also PI12/00330, integrated in the Plan Nacional I+D+I and co-funded by ISCIII-Subdirección General de Evaluación and European Regional Development Fund (ERDF) with both grants awarded to Pere Ginès. Additional funding was provided by CIBEReHD and Fondo de Investigación Sanitaria Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Research Article
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                All relevant data are within the paper and its Supporting Information files.

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