title: Urine Fetuin-A is a biomarker of autosomal dominant polycystic kidney disease progression.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by numerous fluid-filled cysts that frequently result in end-stage renal disease. While promising treatment options are in advanced clinical development, early diagnosis and follow-up remain a major challenge. We therefore evaluated the diagnostic value of Fetuin-A as a new biomarker of ADPKD in human urine.
  
  
  RESULTS
  We found that renal Fetuin-A levels are upregulated in both Pkd1 and Bicc1 mouse models of ADPKD. Measurement by ELISA revealed that urinary Fetuin-A levels were significantly higher in 66 ADPKD patients (17.5 ± 12.5 μg/mmol creatinine) compared to 17 healthy volunteers (8.5 ± 3.8 μg/mmol creatinine) or 50 control patients with renal diseases of other causes (6.2 ± 2.9 μg/mmol creatinine). Receiver operating characteristics (ROC) analysis of urinary Fetuin-A levels for ADPKD rendered an optimum cut-off value of 12.2 μg/mmol creatinine, corresponding to 94% of sensitivity and 60% of specificity (area under the curve 0.74 ; p = 0.0019). Furthermore, urinary Fetuin-A levels in ADPKD patients correlated with the degree of renal insufficiency and showed a significant increase in patients with preserved renal function followed for two years.
  
  
  CONCLUSIONS
  Our findings establish urinary Fetuin-A as a sensitive biomarker of the progression of ADPKD. Further studies are required to examine the pathogenic mechanisms of elevated renal and urinary Fetuin-A in ADPKD.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Bâtiment SV ISREC, Station 19, Lausanne, Switzerland. nathalie.piazzon@unil.ch.|Department of Pharmacology and Toxicology, University of Lausanne (UNIL), Quartier UNIL-CHUV, Lausanne, Switzerland. nathalie.piazzon@unil.ch.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Piazzon
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Bâtiment SV ISREC, Station 19, Lausanne, Switzerland. florian.bernet@epfl.ch.
authors.forename: Florian
authors.initials: F
authors.lastname: Bernet
authors.affiliation: Service of Nephrology, Lausanne University Hospital (CHUV), Lausanne, Switzerland. Linda.Guihard@chuv.ch.
authors.forename: Linda
authors.initials: L
authors.lastname: Guihard
authors.affiliation: Department of Human Genetics, Leiden Univ. Medical Center, Leiden, The Netherlands. W.N.Leonhard@lumc.nl.
authors.forename: Wouter N
authors.initials: WN
authors.lastname: Leonhard
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Bâtiment SV ISREC, Station 19, Lausanne, Switzerland. severine.urfer@epfl.ch.
authors.forename: Séverine
authors.initials: S
authors.lastname: Urfer
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne (UNIL), Quartier UNIL-CHUV, Lausanne, Switzerland. Dmitri.Firsov@unil.ch.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Firsov
authors.affiliation: Department of Pediatrics, Division of Pediatric Nephrology, Lausanne University Hospital (CHUV), Lausanne, Switzerland. Hassib.Chehade@chuv.ch.
authors.forename: Hassib
authors.initials: H
authors.lastname: Chehade
authors.affiliation: Department of Nephrology and Hypertension, Inselspital, Bern, Switzerland. bruno.vogt@insel.ch.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vogt
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne (UNIL), Quartier UNIL-CHUV, Lausanne, Switzerland. sophia.piergiovanni@chuv.ch.
authors.forename: Sophia
authors.initials: S
authors.lastname: Piergiovanni
authors.affiliation: Department of Human Genetics, Leiden Univ. Medical Center, Leiden, The Netherlands. D.J.M.Peters@lumc.nl.
authors.forename: Dorien J M
authors.initials: DJ
authors.lastname: Peters
authors.affiliation: Department of Pharmacology and Toxicology, University of Lausanne (UNIL), Quartier UNIL-CHUV, Lausanne, Switzerland. Olivier.Bonny@chuv.ch.|Service of Nephrology, Lausanne University Hospital (CHUV), Lausanne, Switzerland. Olivier.Bonny@chuv.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bonny
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Bâtiment SV ISREC, Station 19, Lausanne, Switzerland. Daniel.Constam@epfl.ch.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Constam
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000652:urine; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000652:urine; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000473:pathology* / Q000652:urine*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012372:ROC Curve; D015854:Up-Regulation; D060749:alpha-2-HS-Glycoprotein / Q000652:urine*
chemical_list: C540667:Bicc1 protein, mouse; D015415:Biomarkers; D016601:RNA-Binding Proteins; D060749:alpha-2-HS-Glycoprotein