title: Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit.
abstract: 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.
authors.affiliation: Yale University, Section of Nephrology, 950 Campbell Avenue, Box 151B, West Haven, CT 06516, USA. chirag.parikh@yale.edu
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Marek
authors.initials: M
authors.lastname: Ancukiewicz
authors.forename: Charles L
authors.initials: CL
authors.lastname: Edelstein
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000175:diagnosis / Q000652:urine*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D020382:Interleukin-18 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000150:complications
chemical_list: D015415:Biomarkers; D020382:Interleukin-18