title: Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI).
abstract: OBJECTIVE
  Novel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI.
  
  
  METHODS
  We performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Children's Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age.
  
  
  RESULTS
  At long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid-binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls.
  
  
  CONCLUSIONS
  Novel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.
authors.affiliation: Department of Pediatrics, The Heart Institute, Division of Cardiology and Center for Acute Care Nephrology, Division of Nephrology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio David.Cooper@cchmc.org.
authors.forename: David S
authors.initials: DS
authors.lastname: Cooper
authors.affiliation: Center for Acute Care Nephrology, Division of Nephrology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Donna
authors.initials: D
authors.lastname: Claes
authors.affiliation: Department of Pediatrics, The Heart Institute, Division of Cardiology and Center for Acute Care Nephrology, Division of Nephrology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldstein
authors.affiliation: Center for Acute Care Nephrology, Division of Nephrology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: Center for Acute Care Nephrology, Division of Nephrology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Center for Acute Care Nephrology, Division of Nephrology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: Department of Pediatrics, The Heart Institute, Division of Cardiology and Center for Acute Care Nephrology, Division of Nephrology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Krawczeski
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D015415:Biomarkers / Q000652:urine; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D050556:Fatty Acid-Binding Proteins / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007223:Infant; D020382:Interleukin-18 / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000652:urine; D011991:Receptors, Virus
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus
keywords: acute kidney injury; biomarkers; children; chronic kidney disease; follow-up studies; humans; kidney; proteinuria; renal insufficiency, chronic