Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)

Clin J Am Soc Nephrol. 2016 Jan 7;11(1):21-9. doi: 10.2215/CJN.04240415. Epub 2015 Nov 17.


Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Keywords: acute kidney injury; biomarkers; children; chronic kidney disease; follow-up studies; humans; kidney; proteinuria; renal insufficiency, chronic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / urine
  • Acute-Phase Proteins / urine
  • Biomarkers / urine
  • Cardiopulmonary Bypass
  • Child, Preschool
  • Cross-Sectional Studies
  • Fatty Acid-Binding Proteins / urine
  • Female
  • Follow-Up Studies
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Infant
  • Interleukin-18 / urine
  • Lipocalin-2
  • Lipocalins / urine
  • Male
  • Membrane Glycoproteins / urine
  • Proto-Oncogene Proteins / urine
  • Receptors, Virus


  • Acute-Phase Proteins
  • Biomarkers
  • Fatty Acid-Binding Proteins
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Interleukin-18
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins
  • Receptors, Virus