Urine interleukin-18 and cystatin-C as biomarkers of acute kidney injury in critically ill neonates

Pediatr Nephrol. 2012 May;27(5):851-60. doi: 10.1007/s00467-011-2072-x. Epub 2012 Jan 8.


Background: Urinary interleukin-18 and cystatin-C are suggested to be biomarkers for predicting acute kidney injury (AKI). The aims of this study are to examine whether the urinary concentrations of interleukin-18 and cystatin-C vary with gestational age and other factors in non-AKI control neonates, and to determine whether urinary interleukin-18 and cystatin-C can predict AKI development in non-septic critically ill neonates, independently of potential confounders.

Methods: We enrolled 62 non-septic critically ill neonates. Urine was collected every 48-72 h during the first 10 days of life.

Results: Urinary concentration of cystatin-C, but not interleukin-18, decreased with increasing gestational age and body weight, but not with increasing postnatal age in non-AKI control neonates. Both urinary interleukin-18 and cystatin-C were associated with AKI, even after controlling for gestational and postnatal age, birth weight, gender, Apgar score and the score for neonatal acute physiology in non-septic critically ill neonates. Urinary interleukin-18 and cystatin-C had odds ratios of 2.27 and 2.07, and achieved the area under-the-receiver-operating-characteristic curve of 0.72 and 0.92, respectively, for predicting AKI.

Conclusions: The urinary concentration of cystatin-C, but not interleukin-18, may decrease with increasing renal maturity. Both urinary interleukin-18 and cystatin-C are independently predictive of AKI in non-septic critically ill neonates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / urine*
  • Aging / metabolism
  • Apgar Score
  • Biomarkers / urine
  • Birth Weight / physiology
  • Body Weight / physiology
  • Critical Illness
  • Cystatin C / urine*
  • Data Collection
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gestational Age
  • Humans
  • Immunochemistry
  • Infant, Newborn
  • Interleukin-18 / urine*
  • Logistic Models
  • Male
  • Predictive Value of Tests
  • ROC Curve
  • Sex Characteristics


  • Biomarkers
  • Cystatin C
  • Interleukin-18