6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Urinary Proteomics in Predicting Heart Transplantation Outcomes (uPROPHET)—Rationale and database description

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objectives

          Urinary Proteomics in Predicting Heart Transplantation Outcomes (uPROPHET; NCT03152422) aims: (i) to construct new multidimensional urinary proteomic (UP) classifiers that after heart transplantation (HTx) help in detecting graft vasculopathy, monitoring immune system activity and graft performance, and in adjusting immunosuppression; (ii) to sequence UP peptide fragments and to identify key proteins mediating HTx-related complications; (iii) to validate UP classifiers by demonstrating analogy between UP profiles and tissue proteomic signatures (TP) in diseased explanted hearts, to be compared with normal donor hearts; (iv) and to identify new drug targets. This article describes the uPROPHET database construction, follow-up strategies and baseline characteristics of the HTx patients.

          Methods

          HTx patients enrolled at the University Hospital Gasthuisberg (Leuven) collected mid-morning urine samples. Cardiac biopsies were obtained at HTx. UP and TP methods and the statistical work flow in pursuit of the research objectives are described in detail in the Data supplement.

          Results

          Of 352 participants in the UP study (24.4% women), 38.9%, 40.3%, 5.7% and 15.1% had ischemic, dilated, hypertrophic or other cardiomyopathy. The median interval between HTx and first UP assessment (baseline) was 7.8 years. At baseline, mean values were 56.5 years for age, 25.2 kg/m 2 for body mass index, 142.3/84.8 mm Hg and 124.2/79.8 mm Hg for office and 24-h ambulatory systolic/diastolic pressure, and 58.6 mL/min/1.73 m 2 for the estimated glomerular filtration rate. Of all patients, 37.2% and 6.5% had a history of mild (grade = 1B) or severe (grade ≥ 2) cellular rejection. Anti-body mediated rejection had occurred in 6.2% patients. The number of follow-up urine samples available for future analyses totals over 950. The TP study currently includes biopsies from 7 healthy donors and 15, 14, and 3 patients with ischemic, dilated, and hypertrophic cardiomyopathy.

          Conclusions

          uPROPHET constitutes a solid resources for UP and TP research in the field of HTx and has the ambition to lay the foundation for the clinical application of UP in risk stratification in HTx patients.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.

          In 1990, an international grading system for cardiac allograft biopsies was adopted by the International Society for Heart Transplantation. This system has served the heart transplant community well, facilitating communication between transplant centers, especially with regard to patient management and research. In 2004, under the direction of the International Society for Heart and Lung Transplantation (ISHLT), a multidisciplinary review of the cardiac biopsy grading system was undertaken to address challenges and inconsistencies in its use and to address recent advances in the knowledge of antibody-mediated rejection. This article summarizes the revised consensus classification for cardiac allograft rejection. In brief, the revised (R) categories of cellular rejection are as follows: Grade 0 R--no rejection (no change from 1990); Grade 1 R--mild rejection (1990 Grades 1A, 1B and 2); Grade 2 R--moderate rejection (1990 Grade 3A); and Grade 3 R--severe rejection (1990 Grades 3B and 4). Because the histologic sub-types of Quilty A and Quilty B have never been shown to have clinical significance, the "A" and "B" designations have been eliminated. Recommendations are also made for the histologic recognition and immunohistologic investigation of acute antibody-mediated rejection (AMR) with the expectation that greater standardization of the assessment of this controversial entity will clarify its clinical significance. Technical considerations in biopsy processing are also addressed. This consensus revision of the Working Formulation was approved by the ISHLT Board of Directors in December 2004.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

            The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Gene-expression profiling for rejection surveillance after cardiac transplantation.

              Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P=0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P<0.001). Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.) 2010 Massachusetts Medical Society
                Bookmark

                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: VisualizationRole: Writing – review & editing
                Role: SoftwareRole: Writing – review & editing
                Role: Formal analysisRole: SoftwareRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 September 2017
                2017
                : 12
                : 9
                : e0184443
                Affiliations
                [1 ] Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
                [2 ] Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Institute of Hypertension, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
                [3 ] Division of Cardiology, University Hospitals Leuven, Leuven, Belgium
                [4 ] Mosaiques Diagnostics GmbH, Hannover, Germany
                [5 ] Biotechnology Division, Biomedical Research Foundation, Academy of Athens, Athens, Greece
                [6 ] R&D Group VitaK, Maastricht University, Maastricht, The Netherlands
                University of Glasgow, UNITED KINGDOM
                Author notes

                Competing Interests: Esther Nkuipou-Kenfack is an employee of Mosaiques-Diagnostics AG (Hannover, Germany) and advised on the interpretation of the urinary proteomic data and participated in the critical review of the final draft of the manuscript. Her commercial affiliation did not play any role in study design, data collection and analysis, or decision to publish the manuscript and did not influence the statement on data sharing. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-3026-1637
                Article
                PONE-D-17-27950
                10.1371/journal.pone.0184443
                5589218
                28880921
                39ec3b23-f7af-42c7-867e-88ffa46cc0a6
                © 2017 Huang et al

                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
                : 27 July 2017
                : 23 August 2017
                Page count
                Figures: 3, Tables: 5, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100010663, H2020 European Research Council;
                Award ID: 294713
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100010663, H2020 European Research Council;
                Award ID: 713601
                Award Recipient :
                Funded by: Seventh Framework Programme (BE)
                Award ID: 305507
                Award Recipient :
                Funded by: Ministry of the Flemish Community
                Award ID: G.0881.13
                Award Recipient :
                This work was supported by the European Union (HEALTH-F7-305507 HOMAGE, URL: http://www.homage-hf.eu/) and the European Research Council (Advanced Researcher Grant 2011-294713-EPLORE and Proof-of-Concept Grant 713601-uPROPHET; URL: http://cordis.europa.eu/project/rcn/104182_en.html and http://cordis.europa.eu/project/rcn/205861_en.html) and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13, URL: http://www.fwo.be/) currently support the Studies Coordinating Centre in Leuven. The EPLORE grant paid for the urinary proteomic measurements at Mosaiques Diagnostics AG (Hannover, Germany). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Heart
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Urine
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Urine
                Biology and Life Sciences
                Physiology
                Body Fluids
                Urine
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Urine
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Cardiac Transplantation
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Transplantation
                Organ Transplantation
                Cardiac Transplantation
                Research and Analysis Methods
                Database and Informatics Methods
                Biological Databases
                Proteomic Databases
                Biology and Life Sciences
                Biochemistry
                Proteomics
                Proteomic Databases
                Medicine and Health Sciences
                Cardiology
                Cardiomyopathies
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Biology and Life Sciences
                Biochemistry
                Peptides
                Biology and Life Sciences
                Biochemistry
                Proteomics
                Custom metadata
                Consent given by study participants did not include data sharing with third parties. Anonymized data can be made available to investigators for targeted research based on a motivated request to be addressed to the corresponding author via jan.staessen@ 123456med.kuleuven.be .

                Uncategorized
                Uncategorized

                Comments

                Comment on this article