title: Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury.
abstract: BACKGROUND
  New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.
  
  
  METHODS
  This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery.
  
  
  RESULTS
  Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers.
  
  
  CONCLUSIONS
  In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease.
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schley
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Köberle
authors.affiliation: Biomarker Assessments, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Manuilova
authors.affiliation: Biomarker Assessments, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rutz
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Forster
authors.affiliation: Department of Cardiac Surgery, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Weyand
authors.affiliation: Biomarker & Experimental Medicine, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Formentini
authors.affiliation: Biomarker Assessments, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Kientsch-Engel
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Willam
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000503:physiopathology / Q000601:surgery / Q000652:urine*; D000328:Adult; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D015999:Multivariate Analysis; D011182:Postoperative Care; D011300:Preoperative Care; D012307:Risk Factors
chemical_list: D015415:Biomarkers