Christina A de Fontnouvelle1, Jason H Greenberg2, Heather R Thiessen-Philbrook1, Michael Zappitelli3, Jeremy Roth4, Kathleen F Kerr4, Prasad Devarajan5, Michael Shlipak6, Steven Coca7, Chirag R Parikh8. 1. Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut, USA. 2. Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Pediatrics, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA. 3. Department of Pediatrics, Division of Pediatric Nephrology, McGill University Health Centre, Montreal, Quebec, Canada. 4. Department of Biostatistics, University of Washington, Seattle, Washington, USA. 5. Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 6. Division of General Internal Medicine, Veterans Administration Medical Center, University of California, San Francisco, California, USA. 7. Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Internal Medicine, Section of Nephrology, Mount Sinai School of Medicine, New York, New York, USA. 8. Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut, USA; Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut and VA Medical Center, West Haven, Connecticut, USA. Electronic address: chirag.parikh@yale.edu.
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.
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.
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