title: Urinary proteomics in chronic kidney disease: diagnosis and risk of progression beyond albuminuria.
abstract: BACKGROUND
  The contrast between a high prevalence of chronic kidney disease (CKD) and the low incidence of end-stage renal disease highlights the need for new biomarkers of progression beyond albuminuria testing. Urinary proteomics is a promising method, but more studies focusing on progression rate and patients with hypertensive nephropathy are needed.
  
  
  RESULTS
  We analyzed urine samples with capillary electrophoresis coupled to a mass-spectrometer from 18 well characterized patients with CKD stage 4-5 (of whom six with hypertensive nephropathy) and 17 healthy controls. Classification scores based on a previously developed panel of 273 urinary peptides were calculated and compared to urine albumin dipstick results. Urinary proteomics classified CKD with a sensitivity of 0.95 and specificity of 1.00. Overall diagnostic accuracy (area under ROC curve) was 0.98, which was better than for albuminuria (0.85, p = 0.02). Results for hypertensive nephropathy were similar to other CKD diagnoses. Adding the proteomic score to an albuminuria model improved detection of rapid kidney function decline (>4 ml/min/1.73 m(2) per year) substantially: area under ROC curve increased from 0.762 to 0.909 (p = 0.042), and 38% of rapid progressors were correctly reclassified to a higher risk and 55% of slow progressors were correctly reclassified to a lower risk category. Reduced excretion of collagen types I-III, uromodulin, and other indicators of interstitial inflammation, fibrosis and tubular dysfunction were associated with CKD diagnosis and rapid progression. Patients with hypertensive nephropathy displayed the same findings as other types of CKD.
  
  
  CONCLUSIONS
  Urinary proteomic analyses had a high diagnostic accuracy for CKD, including hypertensive nephropathy, and strongly improved identification of patients with rapid kidney function decline beyond albuminuria testing.
authors.affiliation: Department of Nephrology, St Olav University Hospital, Trondheim, Norway ; Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Marius A
authors.initials: MA
authors.lastname: Øvrehus
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Zürbig
authors.affiliation: Renal Research Group, Department of Clinical Medicine, University of Bergen, Bergen, Norway ; Department of Medicine, Haugesund Hospital, Haugesund, Norway.
authors.forename: Bjørn E
authors.initials: BE
authors.lastname: Vikse
authors.affiliation: Department of Nephrology, St Olav University Hospital, Trondheim, Norway ; Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway ; Center of Renal Translational Medicine, University of California San Diego (UCSD), La Jolla, USA.
authors.forename: Stein I
authors.initials: SI
authors.lastname: Hallan
keywords: Albuminuria; Chronic kidney disease; Disease progression; Hypertensive nephropathy; Proteomics; Urine