title: Identification of Molecular Markers of Delayed Graft Function Based on the Regulation of Biological Ageing.
abstract: BACKGROUND
  Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications.
  
  
  METHODS
  The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts.
  
  
  RESULTS
  Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation.
  
  
  CONCLUSIONS
  These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia.
authors.affiliation: University of Glasgow, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, Garscube Estate, Switchback Road, Glasgow, G61 1QH, Scotland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: McGuinness
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), A-6020 Medical University Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Leierer
authors.affiliation: University of Glasgow, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, Garscube Estate, Switchback Road, Glasgow, G61 1QH, Scotland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Shapter
authors.affiliation: University of Glasgow, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, Garscube Estate, Switchback Road, Glasgow, G61 1QH, Scotland.
authors.forename: Suhaib
authors.initials: S
authors.lastname: Mohammed
authors.affiliation: University of Glasgow, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, Garscube Estate, Switchback Road, Glasgow, G61 1QH, Scotland.
authors.forename: Marc
authors.initials: M
authors.lastname: Gingell-Littlejohn
authors.affiliation: NHS Greater Glasgow and Clyde, Renal Transplant Unit, Ward 4c, South Glasgow University Hospital, Glasgow, G51 4TF, Scotland.
authors.forename: David B
authors.initials: DB
authors.lastname: Kingsmore
authors.affiliation: NHS Greater Glasgow and Clyde, Histocompatibility and Immunogenetics, Laboratory Medicine Building, Gartnavel General Hospital, Glasgow, G12 0XL, Scotland.
authors.forename: Ann-Margaret
authors.initials: AM
authors.lastname: Little
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), A-6020 Medical University Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Kerschbaum
authors.affiliation: Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneeberger
authors.affiliation: Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Manuel
authors.initials: M
authors.lastname: Maglione
authors.affiliation: Universitätsklinikum Tübingen, Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie, Transplantationszentrum, D-72076 Tübingen, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Nadalin
authors.affiliation: Universitätsklinikum Tübingen, Klinik für AllgemeineViszeral und Transplantationschirurgie, Chirurgische Studienzentale, D-72076 Tübingen, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Universitätsklinikum Tübingen, Universitätsklinik für Allgemeine, Viszeralund Transplantationschirurgie, CRONA, D-72076 Tübingen, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.affiliation: NHS Greater Glasgow and Clyde, Renal Transplant Unit, Ward 4c, South Glasgow University Hospital, Glasgow, G51 4TF, Scotland.
authors.forename: Emma
authors.initials: E
authors.lastname: Aitken
authors.affiliation: University of Glasgow, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, Garscube Estate, Switchback Road, Glasgow, G61 1QH, Scotland.
authors.forename: Henry
authors.initials: H
authors.lastname: Whalen
authors.affiliation: NHS Greater Glasgow and Clyde, Renal Transplant Unit, Ward 4c, South Glasgow University Hospital, Glasgow, G51 4TF, Scotland.
authors.forename: Marc
authors.initials: M
authors.lastname: Clancy
authors.affiliation: Robertson Centre for Biostatistics, University of Glasgow, Glasgow, Scotland.
authors.forename: Alex
authors.initials: A
authors.lastname: McConnachie
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), A-6020 Medical University Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Koppelstaetter
authors.affiliation: NHS Greater Glasgow and Clyde, Renal Transplant Unit, Ward 4c, South Glasgow University Hospital, Glasgow, G51 4TF, Scotland.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Stevenson
authors.affiliation: University of Glasgow, College of Medical, Veterinary & Life Sciences, Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, Garscube Estate, Switchback Road, Glasgow, G61 1QH, Scotland.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D051799:Delayed Graft Function / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; C531888:MIRN125 microRNA, human; C553315:MIRN217 microRNA, human; D035683:MicroRNAs