Interleukin-8 and Tumor Necrosis Factor Predict Acute Kidney Injury After Pediatric Cardiac Surgery

Abstract

Background: Inflammation is a key component of both acute kidney injury (AKI) and response to cardiopulmonary bypass. Because AKI poses risks to children after cardiac surgery, we investigated the value of inflammatory biomarkers interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) for predicting AKI and other complications.

Methods: We enrolled 412 children between the ages of 1 month and 18 years undergoing cardiopulmonary bypass for cardiac surgery. We collected blood both preoperatively and postoperatively (within 6 hours post-surgery) and measured plasma IL-8 and TNFα.

Results: IL-8 and TNFα did not predict AKI in children <2 years, but were strongly associated with AKI in children ≥2 years. There were significant associations between biomarker levels and age (<2 or ≥2 years). In children ≥2 years, patients in the highest tertile of preoperative IL-8 and postoperative TNFα had 4.9-fold (95% CI: 1.8-13.2) and 3.3-fold (95% CI: 1.2-9.0) higher odds of AKI compared with those in the lowest tertile. Children <2 years with higher biomarker levels also had higher odds of AKI, but the difference was not significant. We also found that postoperative TNFα levels were significantly higher in patients with longer hospital stays, and that both postoperative IL-8 and TNFα levels were significantly higher in patients with longer ventilation lengths. There was no evidence that biomarker levels mediated the association between AKI and length of ventilation; they appear to be independent predictors.

Conclusions: Preoperative IL-8 and postoperative TNFα are significantly associated with higher odds of AKI and greater lengths of hospital stays and ventilator use in children 2 years and older.

Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Blue bars indicate no AKI, grey bars stage 1 AKI, and orange bars stage 2/3 AKI. “Early post-op time” means 0–6 hours postoperative, and “Late post-op” means first non-missing measurement from days 2–5 postoperative. Each bar encompasses IQR of values; black lines are medians. Circles, plus-signs, and crosses are means.

Figure 2

Hospital stay, ICU stay, and ventilation lengths in days by biomarker tertiles. The bars indicate median number of days per biomarker tertile. IL, interleukin; TNF, tumor necrosis factor alpha; T, tertile

Figure 3

Arrows denote the effect of the term at the base on the term at the head. Indirect effects are blue, direct effects are orange. Estimated correlation coefficients are listed. “Standardized” means variables were standardized to have a mean of zero and standard deviation of one before computing estimates. CI, confidence interval; CPB, cardiopulmonary bypass; TNF, tumor necrosis factor alpha; IL, interleukin; LOV, length of ventilation