Research

Serum Interleukin-6 and interleukin-8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case-control study

Kathleen D Liu¹ , Christopher Altmann² , Gerard Smits² , Catherine D Krawczeski³ , Charles L Edelstein² , Prasad Devarajan⁴ and Sarah Faubel²

¹Divisions of Nephrology and Critical Care Medicine, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA, USA

²Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, University of Colorado Denver, Aurora, CO, USA

³Section of Cardiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA

⁴Section of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA

author email corresponding author email

Critical Care 2009, 13:R104doi:10.1186/cc7940

Published:	1 July 2009

Abstract

Introduction

Acute kidney injury (AKI) is associated with high mortality rates. New biomarkers that can identify subjects with early AKI (before the increase in serum creatinine) are needed to facilitate appropriate treatment. The purpose of this study was to test the role of serum cytokines as biomarkers for AKI and prolonged mechanical ventilation.

Methods

This was a case-control study of children undergoing cardiac surgery. AKI was defined as a 50% increase in serum creatinine from baseline within 3 days. Levels of serum interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, IL-17, interferon (IFN)-γ, tumor necrosis factor-α (TNF-α), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using a bead-based multiplex cytokine kit in conjunction with flow-based protein detection and the Luminex LabMAP multiplex system in 18 cases and 21 controls. Levels of IL-6 and IL-8 were confirmed with single-analyte ELISA; IL-18 was also measured with single-analyte ELISA.

Results

IL-6 levels at 2 and 12 hours after cardiopulmonary bypass (CPB) and IL-8 levels at 2, 12 and 24 hours were associated with the development of AKI using the Wilcoxon rank-sum test and after adjustment for age, gender, race, and prior cardiac surgery in multivariate logistic regression analysis. In patients with AKI, IL-6 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation (defined as mechanical ventilation for more than 24 hours postoperatively) by receiver operator curve (ROC) analysis, with an area under the ROC curve of 0.95. IL-8 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation in all patients. Serum IL-18 levels were not different between those with and without AKI.

Conclusions

Serum IL-6 and IL-8 values identify AKI early in patients undergoing CPB surgery. Furthermore, among patients with AKI, high IL-6 levels are associated with prolonged mechanical ventilation, suggesting that circulating cytokines in patients with AKI may have deleterious effects on other organs, including the lungs.