title: Acute Kidney Injury Urine Biomarkers in Very Low-Birth-Weight Infants.
abstract: Serum creatinine (SCr)-based AKI definitions have important limitations, particularly in very low-birth-weight (VLBW) neonates. Urine biomarkers may improve our ability to detect kidney damage. We assessed the association between 14 different urine biomarkers and AKI in VLBW infants.
  
  
  
  We performed a prospective cohort study on 113 VLBW infants (weight ≤1200 g or <31 weeks' gestation) admitted to a regional neonatal intensive care unit at the University of Alabama at Birmingham between February 2012 and June 2013. SCr was measured on postnatal days 1, 2, 3, and 4 and was combined with clinically measured SCr to determine AKI according to Kidney Disease Improving Global Outcomes AKI definition (increase in SCr ≥0.3 mg/dl or ≥50% increase from previous lowest value). Urine was collected on the first 4 days (average number of urine collections, 3; range, 1-4). The maximum urine biomarkers and urine biomarker/creatinine levels were calculated for 12 urine biomarkers, and the minimum urine biomarker and biomarker/creatinine levels were assessed for two urine biomarkers. We compared these values between infants with and those without AKI. Ideal cutoffs, area under the receiver-operating characteristic curve , and area under the curve adjusted for gestational age were calculated.
  
  
  
  Cumulative incidence of AKI during the first 2 postnatal weeks was 28 of 113 (25%). Infants with AKI had higher maximum levels of urine cystatin C, neutrophil gelatinase-associated lipocalin, osteopontin, clusterin, and α glutathione S-transferase (2.0, 1.8, 1.7, 1.7, and 3.7 times higher, respectively) than infants without AKI. In addition, infants with AKI had lower minimum levels of epithelial growth factor and uromodulin than those without AKI (1.4 and 1.6 times lower, respectively). Most but not all participants had their maximum (or minimum) biomarker values preceding AKI. These associations remained after adjustment for gestational age.
  
  
  
  Urine biomarkers measured in the first 4 days of life are associated with AKI during the first postnatal weeks. Further evaluations are necessary to determine whether these biomarkers can predict important clinical outcomes. In addition, intervention studies that use biomarkers to stratify enrollment groups are needed before bedside evaluations can be incorporated into care.
authors.affiliation: Division of Pediatric Nephrology and.
authors.forename: David J
authors.initials: DJ
authors.lastname: Askenazi
authors.affiliation: Division of Pediatric Nephrology and.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Koralkar
authors.affiliation: Division of Neonatology, Department of Pediatrics, and.
authors.forename: Neha
authors.initials: N
authors.lastname: Patil
authors.affiliation: Division of Neonatology, Department of Pediatrics, and.
authors.forename: Brian
authors.initials: B
authors.lastname: Halloran
authors.affiliation: Division of Neonatology, Department of Pediatrics, and.
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Russell
authors.initials: R
authors.lastname: Griffin
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis / Q000652:urine*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D051152:Clusterin / Q000652:urine*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000652:urine*; D004815:Epidermal Growth Factor / Q000652:urine*; D005260:Female; D005865:Gestational Age; D005982:Glutathione Transferase / Q000652:urine*; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000097:blood / Q000652:urine*; D007527:Isoenzymes / Q000652:urine*; D000071068:Lipocalin-2 / Q000652:urine*; D008297:Male; D053495:Osteopontin / Q000652:urine*; D011446:Prospective Studies; D012372:ROC Curve; D013997:Time Factors; D058949:Uromodulin / Q000652:urine*
chemical_list: D015415:Biomarkers; C495242:CLU protein, human; D051152:Clusterin; D055316:Cystatin C; D007527:Isoenzymes; C489506:LCN2 protein, human; D000071068:Lipocalin-2; C548612:UMOD protein, human; D058949:Uromodulin; D053495:Osteopontin; D004815:Epidermal Growth Factor; D003404:Creatinine; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha
keywords: KIM-1; NGAL; acute kidney injury; beta-2 microglobulin; biomarkers; child; creatinine; cystatin c; humans; infant, very low birth weight; intensive care units, neonatal; prospective studies