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Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery

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Abstract

Background

Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of the inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery.

Methods

This is a sub-study of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort, including 106 children ranging in age from 1 month to 18 years undergoing CPB. Plasma IL-6 and IL-10 concentrations were measured preoperatively and postoperatively [day 1 (within 6 h after surgery) and day 3].

Results

Stage 2/3 AKI, defined by at least a doubling of the baseline serum creatinine concentration or dialysis, was diagnosed in 24 (23 %) patients. The preoperative IL-6 concentration was significantly higher in patients with stage 2/3 AKI [median 2.6 pg/mL, interquartile range (IQR) 2.6 0.6–4.9 pg/mL] than in those without stage 2/3 AKI (median 0.6 pg/mL, IQR 0.6–2.2 pg/mL) (p = 0.03). After adjustment for clinical and demographic variables, the highest preoperative IL-6 tertile was associated with a sixfold increased risk for stage 2/3 AKI compared with the lowest tertile (adjusted odds ratio 6.41, 95 % confidence interval 1.16–35.35). IL-6 and IL-10 levels increased significantly after surgery, peaking postoperatively on day 1. First postoperative IL-6 and IL-10 measurements did not significantly differ between patients with stage 2/3 AKI and those without stage 2/3 AKI. The elevated IL-6 level on day 3 was associated with longer hospital stay (p = 0.0001).

Conclusions

Preoperative plasma IL-6 concentration is associated with the development of stage 2/3 AKI and may be prognostic of resource utilization.

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Acknowledgments

The Evidence InvestigatorTM Cytokine Custom Array 4 kits were donated by Randox Laboratories Ltd. This study was supported by the National Institutes of Health (NIH) (R01HL085757 to C.R.P.) to fund the TRIBE-AKI Consortium to study novel biomarkers of AKI in cardiac surgery. J.H.G. is funded by the T32DK007276-35 training grant to the Yale University School of Medicine Section of Nephrology. C.R.P. is supported by the NIH (K24DK090203) and P30 DK079310-07 O’Brien Center Grant. A.X.G., and C.R.P. are also members of the NIH-sponsored Assess, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Consortium (U01DK082185).

The granting agency, Randox Laboratories Ltd., did not participate in the design and conduct of the study, collection, management, analysis, and interpretation of the data, and preparation, review, or approval of the manuscript. The results presented in this article have not been published previously in whole or part, except in abstract form.

Disclosures

Dr. Kavsak has received grants/honorariums/consultant/advisor fees from Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Randox Laboratories, Roche diagnostics, and the Canadian Agency for Drugs and Technologies in Health. He is listed as an inventor on patents filed by McMaster University related to laboratory testing in acute cardiac care.

Dr. P.J. Devereaux is part of a group that has a policy of not accepting honorariums or other payments from industry for their own personal financial gain. They do accept honorariums or other payments from industry to support research endeavors and for reimbursement of costs to participate in meetings such as scientific or advisory committee meetings. Based on study questions he originated and grants he wrote, he has received grants from Abbott Diagnostics, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Covidien, Stryker, and Roche Diagnostics. He has participated in an advisory board meeting for GlaxoSmithKline and an expert panel meeting for Astra Zeneca. He has also participated on a Consultancy Board for Boehringer Ingelheim.

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Authors and Affiliations

  1. Department of Pediatrics, Section of Nephrology, Yale University School of Medicine, New Haven, CT, USA

    Jason H. Greenberg

  2. Program of Applied Translational Research, Yale University School of Medicine, 60 Temple Street, 6th Floor, Suite 6C, New Haven, CT, 06510, USA

    Jason H. Greenberg, William R. Zhang & Chirag R. Parikh

  3. Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada

    Heather R. Thiessen-Philbrook & Amit X. Garg

  4. Division of Pediatric Nephrology, Department of Pediatrics, McGill University Health Centre, Montreal, Quebec, Canada

    Michael Zappitelli

  5. Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Prasad Devarajan

  6. Division of Cardiac Surgery, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada

    Richard Whitlock & John Eikelboom

  7. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

    Peter A. Kavsak

  8. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

    P. J. Devereaux & Colleen Shortt

  9. Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA

    Chirag R. Parikh

  10. VA Medical Center, West Haven, CT, USA

    Chirag R. Parikh

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  1. Jason H. Greenberg
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  2. Richard Whitlock
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  3. William R. Zhang
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  9. P. J. Devereaux
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  10. Colleen Shortt
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  11. Amit X. Garg
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  12. Chirag R. Parikh
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for the TRIBE-AKI Consortium

Corresponding author

Correspondence to Chirag R. Parikh.

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Greenberg, J.H., Whitlock, R., Zhang, W.R. et al. Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery. Pediatr Nephrol 30, 1519–1527 (2015). https://doi.org/10.1007/s00467-015-3088-4

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  • DOI: https://doi.org/10.1007/s00467-015-3088-4

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