title: The urinary proteome as correlate and predictor of renal function in a population study.
abstract: BACKGROUND
  We investigate whether the urinary proteome refines the diagnosis of renal dysfunction, which affects over 10% of the adult population.
  
  
  METHODS
  We measured serum creatinine, estimated glomerular filtration rate (eGFR) and 24-h albuminuria in 797 people randomly recruited from a population. We applied capillary electrophoresis coupled with mass spectrometry to measure multi-dimensional urinary proteomic classifiers developed for renal dysfunction (CKD273) or left ventricular dysfunction (HF1 and HF2). Renal function was followed up in 621 participants and the incidence of cardiovascular events in the whole study population.
  
  
  RESULTS
  In multivariable-adjusted cross-sectional analyses, higher biomarker levels analysed separately or combined by principal component analysis into a single factor (SF), correlated (P ≤ 0.010) with worse renal function. Over 4.8 years, higher HF1 and SF predicted (P ≤ 0.014) lowering of eGFR; higher HF2 predicted (P ≤ 0.049) increase in serum creatinine and decrease eGFR. HF1, HF2 and SF predicted progression from CKD Stages 2 or ≤2 to Stage ≥3, with risk estimates for a 1-SD increment in the urinary biomarkers ranging from 38 to 71% (P ≤ 0.039). HF1, HF2 and SF yielded a net reclassification improvement of 31-51% (P ≤ 0.029). Over 6.1 years, 47 cardiovascular events occurred. HF2 and SF, independent of baseline eGFR, 24-h albuminuria and other covariables were significant predictors of cardiovascular complications with risk estimates for 1-SD increases ranging from 32 to 41% (P ≤ 0.047).
  
  
  CONCLUSIONS
  The urinary proteome refines the diagnosis of existing or progressing renal dysfunction and predicts cardiovascular complications.
authors: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Yu-Mei
authors: YM
authors: Gu
authors: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Lutgarde
authors: L
authors: Thijs
authors: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Yan-Ping
authors: YP
authors: Liu
authors: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Zhenyu
authors: Z
authors: Zhang
authors: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Lotte
authors: L
authors: Jacobs
authors: Mosaiques Diagnostic and Therapeutics AG, Hannover, Germany.
authors: Thomas
authors: T
authors: Koeck
authors: Mosaiques Diagnostic and Therapeutics AG, Hannover, Germany.
authors: Petra
authors: P
authors: Zürbig
authors: Hannover Medical School, Institute of Clinical Chemistry, Hannover, Germany.
authors: Ralf
authors: R
authors: Lichtinghagen
authors: Hannover Medical School, Institute of Clinical Chemistry, Hannover, Germany.
authors: Korbinian
authors: K
authors: Brand
authors: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Tatiana
authors: T
authors: Kuznetsova
authors: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium Department of Health Sciences and San Paolo Hospital, School of Medicine, University of Milan, Milan, Italy.
authors: Laura
authors: L
authors: Olivi
authors: Research Unit Molecular and Vascular Biology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Peter
authors: P
authors: Verhamme
authors: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors: Christian
authors: C
authors: Delles
authors: Mosaiques Diagnostic and Therapeutics AG, Hannover, Germany BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors: Harald
authors: H
authors: Mischak
authors: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium Department of Epidemiology, Maastricht University, Maastricht, the Netherlands.
authors: Jan A
authors: JA
authors: Staessen
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology* / Q000652:urine; D001530:Belgium / Q000453:epidemiology; D015415:Biomarkers / Q000652:urine*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011379:Prognosis; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000503:physiopathology / Q000652:urine*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: chronic kidney disease; eGFR; population science; renal function; urinary proteomics