title: Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans.
abstract: Acute kidney injury (AKI) is associated with high morbidity and mortality. The lack of sensitive and specific injury biomarkers has greatly impeded the development of therapeutic strategies to improve outcomes of AKI.The unique objective of this study was to evaluate the diagnostic performance of nine urinary biomarkers of AKI-kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), hepatocyte growth factor (HGF), cystatin C (Cys), N-acetyl-beta-D-glucosaminidase (NAG), vascular endothelial growth factor (VEGF), chemokine interferon-inducible protein 10 (IP-10; CXCL10), and total protein-in a cross-sectional comparison of 204 patients with or without AKI.Median urinary concentrations of each biomarker were significantly higher in patients with AKI than in those without AKI (p < 0.001). The area under the receiver operating characteristics curve (AUC-ROC) for the combination of biomarkers using a logic regression model [risk score of 2.93*(NGAL > 5.72 and HGF > 0.17) + 2.93*(PROTEIN > 0.22) -2*(KIM < 0.58)] was greater (0.94) than individual biomarker AUC-ROCs. Age-adjusted levels of urinary KIM-1, NAG, HGF, VEGF, and total protein were significantly higher in patients who died or required renal replacement therapy (RRT) when compared to those who survived and did not require RRT.Our results demonstrate the comparative value of multiple biomarkers in the diagnosis and prognosis of AKI.
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Vishal S
authors.initials: VS
authors.lastname: Vaidya
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ferguson
authors.forename: Fitz B
authors.initials: FB
authors.lastname: Collings
authors.forename: Kelsey
authors.initials: K
authors.lastname: Sunderland
authors.forename: Costas
authors.initials: C
authors.lastname: Gioules
authors.forename: Gary
authors.initials: G
authors.lastname: Bradwin
authors.forename: Roland
authors.initials: R
authors.lastname: Matsouaka
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: Gary C
authors.initials: GC
authors.lastname: Curhan
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000652:urine; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D017582:Renal Replacement Therapy; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers