Background In acute renal failure (ARF) the production and clearance of serum creatinine is affected by several non-renal factors and the serum creatinine rises days after initial renal tubular injury. Thus, a urinary biomarker of renal injury is being sought. We have demonstrated that IL-18 is a mediator of ischemic ARF in mice and that urinary IL-18 levels are elevated in established human ARF. As a next step we investigated the performance of urine IL-18 test as an early diagnostic marker of ARF.
Methods We performed a nested case-control study within the acute respiratory distress syndrome (ARDS) network trial. ARF was defined as an increase in serum creatinine by at least 50% from baseline within the first 6 days of ARDS study enrollment. 52 cases of ARF were eligible for our study. Each case of ARF was randomly matched with 2 controls that did not develop ARF. Urine samples were collected on study days 0, 1 and 3 and a total of 400 urine specimens were analyzed.
Results Median urine IL-18 levels were significantly higher in ARF cases as compared to controls on day 0 (126 vs. 0), day 1 (65 vs. 0) and day 3 (88 vs. 0) (P≤ 0.001). On multivariable analysis after adjusting for demographic and clinical variables, urine IL-18 values predicted development of ARF 24 and 48 hours later. The adjoining figure demonstrates that urine IL-18 performs well as a diagnostic test with an area under the receiver operator characteristic curve of 73% at 24 hours before clinical diagnosis. The sensitivity and specificity range from 75% to 98% (Figure). The urine IL-18 values were also significantly different between survivors and non-survivors with ARF on days 0, 1 and 3. (P ≤ 0.05).
Conclusion Urinary IL-18 test can be used for the early diagnosis and risk-stratification of ARF in ICU.