title: A urinary proteome-based classifier for the early detection of decline in glomerular filtration.
abstract: BACKGROUND
  Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be late-stage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m 2 .
  
  
  METHODS
  A total of 2672 patients with different CKD stages were included in the study. Of these, 394 individuals displayed a decline in eGFR of >5 mL/min/1.73 m 2 /year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of ≥80, 70-79, 60-69, 50-59, 40-49, 30-39 and <29 mL/min/1.73 m 2 . In addition, areas under the curve for CKD273 and UAE were calculated.
  
  
  RESULTS
  In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function.
  
  
  CONCLUSIONS
  These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE.
authors.affiliation: Mosaiques Diagnostics, Hanover, Germany.|Charité-Universitatsmedizin, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pontillo
authors.affiliation: Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors.forename: Lotte
authors.initials: L
authors.lastname: Jacobs
authors.affiliation: Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.|R&D VitaK Group, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
authors.affiliation: Institute of Metabolic and Cardiovascular Diseases, Inserm U1048, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.|University of Aarhus, Aarhus, Denmark.|Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hiddo J L
authors.initials: HJL
authors.lastname: Heerspink
authors.affiliation: Mosaiques Diagnostics, Hanover, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Siwy
authors.affiliation: University of Glasgow, Glasgow, UK.
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.affiliation: Biomedical Research Foundation, Academy of Athens, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Vlahou
authors.affiliation: Mosaiques Diagnostics, Hanover, Germany.|University of Glasgow, Glasgow, UK.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Ray
authors.initials: R
authors.lastname: Vanholder
authors.affiliation: Mosaiques Diagnostics, Hanover, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Zürbig
authors.affiliation: Charité-Universitatsmedizin, Berlin, Germany.|Institute for Molecular Cardiovascular Research, University Hospital RWTH, Aachen, Germany.|Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands.
authors.forename: Joachim
authors.initials: J
authors.lastname: Jankowski
mesh_terms: D015415:Biomarkers / Q000652:urine*; D015331:Cohort Studies; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D051436:Renal Insufficiency, Chronic / Q000145:classification* / Q000175:diagnosis* / Q000652:urine
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: CKD273; albuminuria; chronic kidney disease; peptides; proteome analysis; urine