Article Text

  1. C. R. Parikh1,
  2. E. Abraham1,
  3. M. Ancukiewicz2,
  4. C. L. Edelstein1
  1. 1University of Colorado Health Sciences Center, Denver, CO
  2. 2Harvard Medical School, Boston, MA


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.

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