Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children

Kimberly K Washburn, Michael Zappitelli, Ayse A Arikan, Laura Loftis, Rajesh Yalavarthy, Chirag R Parikh, Charles L Edelstein, Stuart L Goldstein
Nephrology, Dialysis, Transplantation 2008, 23 (2): 566-72

BACKGROUND: Urinary interleukin-18 (uIL-18) is an earlier acute kidney injury (AKI) biomarker than serum creatinine (SCr) in specific populations. In the present study, the relationship between uIL-18 and AKI was determined in a heterogeneous group of critically ill children.

METHODS: We studied critically ill children to determine whether uIL-18 was an early predictor of AKI. SCr was determined daily for up to 14 days from mechanical ventilation initiation and up to four serial urine specimens were collected for the uIL-18 measurement. AKI was graded by paediatric modified risk, injury, failure, loss, end-stage kidney disease (pRIFLE) criteria. Day 0 was defined as the day of attaining pRIFLE AKI.

RESULTS: One hundred thirty-seven children aged 6.5 +/- 6.4 years (53% male) were studied. The peak levels of IL-18 correlated with the severity of AKI by pRIFLE classification (P < 0.05). In non-septic AKI patients, uIL-18 rose to a level higher than control levels 2 days prior to a significant rise in SCr. Urinary IL-18 concentration from the first urine specimen was associated with AKI development within 48 h (odds ratio = 3.5, P < 0.05) independent of the paediatric risk of mortality (PRISM II) score. Urinary IL-18 concentration > or = 100 pg/ml had a specificity and negative predictive value of 81 and 83% to predict AKI development within 24 h. Urinary IL-18 > or = 200 pg/ml collected within 24 h of Day 0 had a specificity and positive predictive value of 93 and 88% respectively to predict the AKI duration > or = 48 h. Urinary IL-18 was associated with mortality (odds ratio = 1.29, P < 0.05), independent of the PRISM II score.

CONCLUSIONS: Urinary IL-18 rises prior to SCr in non-septic critically ill children, predicts severity of AKI and is an independent predictor of mortality.

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