title: Urine peptidome analysis predicts risk of end-stage renal disease and reveals proteolytic pathways involved in autosomal dominant polycystic kidney disease progression.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by slowly progressive bilateral renal cyst growth ultimately resulting in loss of kidney function and end-stage renal disease (ESRD). Disease progression rate and age at ESRD are highly variable. Therapeutic interventions therefore require early risk stratification of patients and monitoring of disease progression in response to treatment.
  
  
  
  We used a urine peptidomic approach based on capillary electrophoresis-mass-spectrometry (CE-MS) to identify potential biomarkers reflecting the risk for early progression to ESRD in the Consortium of Radiologic Imaging in Polycystic Kidney Disease (CRISP) cohort.
  
  
  
  A biomarker-based classifier consisting of 20 urinary peptides allowed the prediction of ESRD within 10-13 years of follow-up in patients 24-46 years of age at baseline. The performance of the biomarker score approached that of height-adjusted total kidney volume (htTKV) and the combination of the biomarker panel with htTKV improved prediction over either one alone. In young patients (<24 years at baseline), the same biomarker model predicted a 30 mL/min/1.73 m 2 glomerular filtration rate decline over 8 years. Sequence analysis of the altered urinary peptides and the prediction of the involved proteases by in silico analysis revealed alterations in distinct proteolytic pathways, in particular matrix metalloproteinases and cathepsins.
  
  
  
  We developed a urinary test that accurately predicts relevant clinical outcomes in ADPKD patients and suggests altered proteolytic pathways involved in disease progression.
authors.affiliation: Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany.|Charite-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Pejchinovski
authors.affiliation: Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Siwy
authors.affiliation: Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Metzger
authors.affiliation: Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Dakna
authors.affiliation: Mosaiques Diagnostics and Therapeutics AG, Hannover, Germany.|BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
authors.affiliation: Universitätsklinikum RWTH Aachen, Institute of Molecular Cardiovascular Research, Aachen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Jankowski
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kyongtae T
authors.initials: KT
authors.lastname: Bae
authors.affiliation: Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Arlene B
authors.initials: AB
authors.lastname: Chapman
authors.affiliation: Department of Internal Medicine, Renal Unit, Cantonal Hospital Frauenfeld, Frauenfeld, Switzerland.
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Kistler
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine; D018450:Disease Progression; D019075:Electrophoresis, Capillary; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010455:Peptides / Q000652:urine*; D016891:Polycystic Kidney, Autosomal Dominant / Q000652:urine*; D012306:Risk; D016482:Urinalysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010455:Peptides
keywords: ADPKD; ESRD; progression; proteases prediction; urinary peptides