title: Cardiopulmonary bypass is associated with hemolysis and acute kidney injury in neonates, infants, and children*.
abstract: OBJECTIVE
  This pilot study assesses the degree of hemolysis induced by cardiopulmonary bypass and determines its association with acute kidney injury in pediatric patients. Further, it evaluates the degree to which the use of urinary biomarkers neutrophil gelatinase-associated lipocalin and cystatin C correlate with the presence of acute kidney injury and hemolysis following cardiopulmonary bypass.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  A 13-bed pediatric cardiac ICU in a university hospital.
  
  
  METHODS
  Children undergoing cardiac surgery with the use of cardiopulmonary bypass.
  
  
  METHODS
  None.
  
  
  RESULTS
  Blood and urine samples were obtained at multiple time points before and after cardiopulmonary bypass. Hemolysis was assessed by measuring levels of plasma hemoglobin and haptoglobin. Acute kidney injury was defined as a doubling in serum creatinine from preoperative baseline and by using the pediatric-modified RIFLE criteria. Urinary neutrophil gelatinase-associated lipocalin and cystatin C levels were measured. A total of 40 patients (range, 3 d to 4.8 yr) were enrolled. Plasma hemoglobin levels increased markedly on separation from cardiopulmonary bypass with a concurrent decrease in haptoglobin. This was associated with an increase in protein oxidation in the plasma. Hemolysis was more evident in younger patients with a longer duration of bypass and in those requiring a blood-primed circuit. Forty percent of patients had a doubling in serum creatinine and acute kidney injury was developed in 88% of patients when defined by the pediatric-modified RIFLE criteria. Controlling for cardiopulmonary bypass time, persistently elevated levels of plasma hemoglobin were associated with a five-fold increase in acute kidney injury. Further, urinary neutrophil gelatinase-associated lipocalin measured 2 hours after separation from cardiopulmonary bypass was associated with acute kidney injury and with elevations in plasma hemoglobin.
  
  
  CONCLUSIONS
  Cardiopulmonary bypass in pediatric patients results in significant hemolysis, which is associated with the development of acute kidney injury. The biomarker neutrophil gelatinase-associated lipocalin correlates with both acute kidney injury and hemolysis in this population.
authors.affiliation: 1Department of Pediatrics, Duke University, Durham, NC. 2Duke Clinical Research Institute, Durham, NC. 3Department of Surgery, Duke University, Durham, NC.
authors.forename: Lara S
authors.initials: LS
authors.lastname: Mamikonian
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Mamo
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
authors.forename: Jeannie
authors.initials: J
authors.lastname: Koo
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lodge
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Turi
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology*; D000209:Acute-Phase Proteins / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D055316:Cystatin C / Q000652:urine*; D005260:Female; D006242:Haptoglobins / Q000032:analysis; D006461:Hemolysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D007677:Kidney Function Tests; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; D006242:Haptoglobins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins