title: Renal function and novel urinary biomarkers in infants with neonatal encephalopathy.
abstract: OBJECTIVE
  Perinatal asphyxia is associated with multi-organ injury including acute kidney injury (AKI). New urinary biomarkers may detect more subtle renal injury.
  
  
  METHODS
  Urinary biomarkers (albumin, beta-2 microglobulin, cystatin-C, epidermal growth factor, neutrophil gelatinase-associated lipocalin, osteopontin, uromodulin) were serially measured from days 1 to 7 in term infants with perinatal asphyxia and controls and compared to 'Kidney Disease Improving Global Outcome' scoring of renal injury and to encephalopathy grade.
  
  
  RESULTS
  A total of 255 urine samples were taken from infants exposed to perinatal asphyxia (n = 82) and term controls (n = 10). Thirty-nine infants underwent therapeutic hypothermia, four died and 30 infants had acute kidney injury. Infants with acute kidney injury had significantly higher levels of urinary albumin (day 2), cystatin-C (days 1, 2, 3 and 7), neutrophil gelatinase-associated lipocalin (days 2, 3 and 7) and osteopontin (days 2, 3 and 7) and lower epidermal growth factor and uromodulin (day 1) compared to those without AKI. Day 2 cystatin-C predicted AKI with an area under receiver operating characteristic curve of 0.89, p < 0.001, cut-off 9.8 × 104pg/mL. NE grade II/III infants had significantly elevated levels of urinary cystatin-C, neutrophil gelatinase-associated lipocalin and decreased EGF compared to grade 0/I infants.
  
  
  CONCLUSIONS
  Asphyxiated infants who develop acute kidney injury have significantly altered urinary biomarkers postnatally. Validation of neonatal AKI urinary biomarkers in a large prospective study is required. Long-term follow-up of infants post-asphyxial insult for chronic renal injury is advised.
authors.affiliation: Department of Neonatology, National Maternity Hospital, Dublin, Ireland.|National Children's Research Centre, Crumlin, Dublin, Ireland.|Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Deirdre U
authors.initials: DU
authors.lastname: Sweetman
authors.affiliation: Department of Neonatology, National Maternity Hospital, Dublin, Ireland.|UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: Chike
authors.initials: C
authors.lastname: Onwuneme
authors.affiliation: UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: William R
authors.initials: WR
authors.lastname: Watson
authors.affiliation: UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: Amanda
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: Department of Neonatology, National Maternity Hospital, Dublin, Ireland.|UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
authors.forename: John F A
authors.initials: JF
authors.lastname: Murphy
authors.affiliation: National Children's Research Centre, Crumlin, Dublin, Ireland. eleanor.molloy@tcd.ie.|Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland. eleanor.molloy@tcd.ie.|UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland. eleanor.molloy@tcd.ie.|Department of Paediatrics, Trinity College Dublin, National Children's Hospital, Tallaght & Coombe Women's and Infant's University Hospital, Dublin, Ireland. eleanor.molloy@tcd.ie.
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Molloy
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000209:etiology / Q000652:urine; D001238:Asphyxia Neonatorum / Q000150:complications*; D015415:Biomarkers / Q000652:urine; D001927:Brain Diseases / Q000151:congenital* / Q000209:etiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D007494:Ireland; D008297:Male; D012372:ROC Curve; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers
keywords: Acute kidney injury; Hypoxic-ischaemic encephalopathy; Perinatal asphyxia; Urinary cystatin-C; Urinary neutrophil gelatinase-associated lipocalin