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Urine IL-18 Is an Early Diagnostic Marker for Acute Kidney Injury and Predicts Mortality in the Intensive Care Unit

Chirag R. Parikh^*, Edward Abraham, Marek Ancukiewicz, Charles L. Edelstein for the Acute Respiratory Distress Syndrome (ARDS) Network

^* Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut; Divisions of Pulmonary and Critical Care and Nephrology, University of Colorado Health Sciences Center, Denver, Colorado; and Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Address correspondence to: Dr. Chirag R. Parikh, Yale University, Section of Nephrology, 950 Campbell Avenue, Box 151B, West Haven, CT 06516. Phone: 203-932-5711 ext. 4300; Fax: 203-937-4932; E-mail: chirag.parikh{at}yale.edu

Received for publication March 1, 2005. Accepted for publication July 21, 2005.

Serum creatinine is not an ideal marker of renal function in patients with acute kidney injury (AKI). Previous studies demonstrated that urinary IL-18 is increased in human AKI. Thus, whether urine IL-18 is an early diagnostic marker of AKI was investigated. A nested case-control study was performed within the Acute Respiratory Distress Syndrome (ARDS) Network trial. AKI was defined as an increase in serum creatinine by at least 50% within the first 6 d of ARDS study enrollment. A total of 400 urine specimens that were collected on study days 0, 1, and 3 of the ARDS trial were available from 52 case patients and 86 control patients. The data were analyzed in a cross-sectional manner and according to the time before development of AKI. The median urine IL-18 levels were significantly different at 24 and 48 h before AKI in case patients as compared with control patients. On multivariable analysis, urine IL-18 values predicted development of AKI 24 and 48 h later after adjustment for demographics, sepsis, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) III score, serum creatinine, and urine output. Urine IL-18 levels of >100 pg/ml are associated with increased odds of AKI of 6.5 (95% confidence interval 2.1 to 20.4) in the next 24 h. On diagnostic performance testing, urine IL-18 demonstrates an area under the receiver operating characteristic curve of 73% to predict AKI in the next 24 h. The urine IL-18 values were also significantly different between survivors and nonsurvivors (P < 0.05), and on multivariable analysis, the urine IL-18 value on day 0 is an independent predictor of mortality. Urinary IL-18 levels can be used for the early diagnosis of AKI. Urine IL-18 levels also predict the mortality of patients who have ARDS and are in the intensive care unit.

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