Serum Interleukin-18 at Commencement of Renal Replacement Therapy Predicts Short-Term Prognosis in Critically Ill Patients with Acute Kidney Injury

BACKGROUND: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) in critically ill patients results in a high hospital mortality. Outcome prediction in this selected high-risk collective is challenging due to the lack of appropriate biomarkers. The aim of this study was to identify outcome-specific biomarkers in this patient population. METHODOLOGY/PRINCIPAL FINDINGS: Serum samples were collected from 101 critically ill patients with AKI at the initiation of RRT in intensive care units (ICUs) of a tertiary care university hospital between August 2008 and March 2011. Measurements of serum levels of cystatin C (CysC), neutrophil gelatinase-associated lipocalin, and interleukin-18 (IL-18) were performed. The primary outcome measure was hospital mortality. The observed overall mortality rate was 56.4% (57/101). Multiple logistic regression analysis indicated that the serum IL-18 and CysC concentrations and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of RRT were independent predictors of hospital mortality. The APACHE III score had the best discriminatory power (0.872±0.041, p<0.001), whereas serum IL-18 had the best Youden index (0.65) and the highest correctness of prediction (83%). Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for serum IL-18 <1786 pg/ml vs. ≥1786 pg/ml in these critically ill patients. CONCLUSIONS: In this study, we confirmed the grave prognosis for critically ill patients at the commencement of RRT and found a strong correlation between serum IL-18 and the hospital mortality of ICU patients with dialysis-dependent AKI. In addition, we demonstrated that the APACHE III score has the best discriminative power for predicting hospital mortality in these critically ill patients.