title: Urinary biomarker incorporation into the renal angina index early in intensive care unit admission optimizes acute kidney injury prediction in critically ill children: a prospective cohort study.
abstract: The inconsistent ability of novel biomarkers to predict acute kidney injury (AKI) across heterogeneous patients and illnesses limits integration into routine practice. We previously retrospectively validated the ability of the renal angina index (RAI) to risk-stratify patients and provide context for confirmatory serum biomarker testing for the prediction of severe AKI.
  
  
  
  We conducted this first prospective study of renal angina to determine whether the RAI on the day of admission (Day0) risk-stratified critically ill children for 'persistent, severe AKI' on Day 3 (Day3-AKI: KDIGO Stage 2-3) and whether incorporation of urinary biomarkers in the RAI model optimized AKI prediction.
  
  
  
  A total of 184 consecutive patients (52.7% male) were included. Day0 renal angina was present (RAI ≥8) in 60 (32.6%) patients and was associated with longer duration of mechanical ventilation (P = 0.04), higher number of organ failure days (P = 0.003) and increased mortality (P < 0.001) than in patients with absence of renal angina. Day3-AKI was present in 15/156 (9.6%) patients; 12/15 (80%) fulfilled Day0 renal angina. Incorporation of urinary biomarkers into the RAI model increased the specificity and positive likelihood, and demonstrated net reclassification improvement (P < 0.001) for the prediction of Day3-AKI. Inclusion of urinary neutrophil gelatinase-associated lipocalin increased the area under the curve receiver-operating characteristic of RAI for Day3-AKI from 0.80 [95% confidence interval (CI): 0.58, 1.00] to 0.97 (95% CI: 0.93, 1.00).
  
  
  
  We have now prospectively validated the RAI as a functional risk stratification methodology in a heterogeneous group of critically ill patients, providing context to direct measurement of novel urinary biomarkers and improving the prediction of severe persistent AKI.
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Shina
authors.initials: S
authors.lastname: Menon
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldstein
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Theresa
authors.initials: T
authors.lastname: Mottes
authors.affiliation: Department of Biostatistics, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA Department of Pediatrics, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Fei
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kaddourah
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Terrell
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Arnold
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, OH, USA Division of Critical Care, Cincinnati Children's Hospital and Medical Center, Cincinnati, OH, USA.
authors.forename: Rajit K
authors.initials: RK
authors.lastname: Basu
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness; D042241:Early Diagnosis; D005260:Female; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007223:Infant; D015278:Intensive Care Units, Pediatric; D007668:Kidney / Q000098:blood supply / Q000473:pathology*; D000071068:Lipocalin-2 / Q000652:urine*; D008297:Male; D011446:Prospective Studies; D012372:ROC Curve; D012720:Severity of Illness Index; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000071068:Lipocalin-2
keywords: acute kidney injury; biomarkers; critical care; renal angina index; risk stratification