title: Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy.
abstract: BACKGROUND
  Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273).
  
  
  METHODS
  In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier.
  
  
  RESULTS
  We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found.
  
  
  CONCLUSIONS
  We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany Charité-Universitaetsmedizin Berlin, Medizinische Klinik IV, Berlin, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Siwy
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: RD Néphrologie, Montpellier, France Néphrologie Dialyse St Guilhem, Sète, France Service de Néphrologie, Dialyse Péritonéale et Transplantation, Montpellier, France.
authors.forename: Angel
authors.initials: A
authors.lastname: Argiles
authors.affiliation: Department of Internal Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Nephrology and KfH Renal Unit, Hospital St. Georg, Leipzig, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Beige
authors.affiliation: Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Boucek
authors.affiliation: Institut für Klinische Chemie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Korbinian
authors.initials: K
authors.lastname: Brand
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Delles
authors.affiliation: RD Néphrologie, Montpellier, France.
authors.forename: Flore
authors.initials: F
authors.lastname: Duranton
authors.affiliation: IIS-Fundacion Jimenez Diaz/UAM/IRSIN and REDIREN, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Fernandez-Fernandez
authors.affiliation: Charité-Universitaetsmedizin Berlin, Medizinische Klinik IV, Berlin, Germany.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Jankowski
authors.affiliation: HealthPlus Diabetes & Endocrinology Center, Abu Dhabi, UAE.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al Khatib
authors.affiliation: HealthPlus Diabetes & Endocrinology Center, Abu Dhabi, UAE.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kunt
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Lajer
authors.affiliation: Institut für Klinische Chemie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Lindhardt
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.affiliation: Department of Internal Medicine, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands Department of Clinical Pharmacology, University Medical Center Groningen, Groningen and University of Groningen, The Netherlands.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Diabetes Center, Second Department of Medicine, Athens University Medical School, Hippokration Hospital, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Noutsou
authors.affiliation: IIS-Fundacion Jimenez Diaz/UAM/IRSIN and REDIREN, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Petrie
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Roob
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark HEALTH, University of Aarhus, Aarhus, Denmark Faculty of Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases 'Aldo e Cele Daccò', Bergamo, Italy Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.affiliation: Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Rychlik
authors.affiliation: Division of Nephrology, University Hospital, Zürich, Switzerland.
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Serra
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Snell-Bergeon
authors.affiliation: Department of Nephrology, University of Skopje, Skopje, Macedonia.
authors.forename: Goce
authors.initials: G
authors.lastname: Spasovski
authors.affiliation: Department of Nephrology, University of Skopje, Skopje, Macedonia.
authors.forename: Olivera
authors.initials: O
authors.lastname: Stojceva-Taneva
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases 'Aldo e Cele Daccò', Bergamo, Italy.
authors.forename: Matias
authors.initials: M
authors.lastname: Trillini
authors.affiliation: Hannover Clinical Trial Center, Hannover, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: von der Leyen
authors.affiliation: Human Nutrition & Metabolism Research and Training Center, Institute of Molecular Biosciences, Karl-Franzens University of Graz, Graz, Austria.
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Winklhofer-Roob
authors.affiliation: Mosaiques Diagnostics GmbH, Hanover, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Zürbig
authors.affiliation: Charité-Universitaetsmedizin Berlin, Medizinische Klinik IV, Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Jankowski
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis / Q000652:urine; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D057786:Peptidomimetics / Q000652:urine*; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*
chemical_list: D057786:Peptidomimetics
keywords: biomarkers; chronic kidney disease; diabetic nephropathy; diagnosis; urine proteomics