Novel Serum and Urine Markers for Pediatric Appendicitis

Authors

  • Anupam B. Kharbanda MD, MSc,

    1. From the Division of Pediatric Emergency Medicine (AK, YC, PSD) and the Department of Pathology and Cell Biology (AJR, KL), Columbia University College of Physicians and Surgeons, New York, NY. Dr. Kharbanda is currently with the Division of Pediatric Emergency Medicine, University of Minnesota, Minneapolis, MN.
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  • Alex J. Rai PhD,

    1. From the Division of Pediatric Emergency Medicine (AK, YC, PSD) and the Department of Pathology and Cell Biology (AJR, KL), Columbia University College of Physicians and Surgeons, New York, NY. Dr. Kharbanda is currently with the Division of Pediatric Emergency Medicine, University of Minnesota, Minneapolis, MN.
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  • Yohaimi Cosme MD,

    1. From the Division of Pediatric Emergency Medicine (AK, YC, PSD) and the Department of Pathology and Cell Biology (AJR, KL), Columbia University College of Physicians and Surgeons, New York, NY. Dr. Kharbanda is currently with the Division of Pediatric Emergency Medicine, University of Minnesota, Minneapolis, MN.
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  • Khin Liu,

    1. From the Division of Pediatric Emergency Medicine (AK, YC, PSD) and the Department of Pathology and Cell Biology (AJR, KL), Columbia University College of Physicians and Surgeons, New York, NY. Dr. Kharbanda is currently with the Division of Pediatric Emergency Medicine, University of Minnesota, Minneapolis, MN.
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  • Peter S. Dayan MD, MSc

    1. From the Division of Pediatric Emergency Medicine (AK, YC, PSD) and the Department of Pathology and Cell Biology (AJR, KL), Columbia University College of Physicians and Surgeons, New York, NY. Dr. Kharbanda is currently with the Division of Pediatric Emergency Medicine, University of Minnesota, Minneapolis, MN.
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  • Presented in part at the annual meeting of Pediatric Academic Societies, Vancouver, British Columbia, Canada, May 2010.

  • Supported by Grant UL1 RR024156 from the National Center for Research Resources (NICRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. In addition, ABK received salary support through the Empire Clinical Research Program (New York State).

  • The authors have no relevant financial information or potential conflicts of interest to disclose.

  • Supervising Editor: Bema Bonsu, MD.

Address for correspondence and reprints: Anupam B. Kharbanda, MD, MSc; e-mail: abk@umn.edu.

Abstract

ACADEMIC EMERGENCY MEDICINE 2012; 19: 56–62 © 2012 by the Society for Academic Emergency Medicine

Abstract

Objectives:  The objective was to describe the association between two novel biomarkers, calprotectin and leucine-rich alpha glycoprotein-1 (LRG), and appendicitis in children.

Methods:  This was a prospective, cross-sectional study of children 3 to 18 years old presenting to a pediatric emergency department (ED) with possible appendicitis. Blood and urine samples were assayed for calprotectin and LRG via enzyme-linked immunosorbent assay (ELISA). Final diagnosis was determined by histopathology or telephone follow-up. Biomarker levels were compared for subjects with and without appendicitis. Recursive partitioning was used to identify thresholds that predicted appendicitis.

Results:  Of 176 subjects, mean (±SD) age was 11.6 (±4.0) years and 52% were male. Fifty-eight patients (34%) were diagnosed with appendicitis. Median plasma calprotectin, serum LRG, and urine LRG levels were higher in appendicitis versus nonappendicitis (p < 0.008). When stratified by perforation status, median plasma calprotectin and serum LRG levels were higher in nonperforated appendicitis versus nonappendicitis (p < 0.01). Median serum LRG, urine LRG, and plasma calprotectin levels were higher in perforated appendicitis compared to nonperforated appendicitis (p < 0.05). Urine calprotectin did not differ among groups. A serum LRG < 40,150 ng/mL, a urine LRG < 42 ng/mL, and a plasma calprotectin < 159 ng/mL, each provided a sensitivity and negative predictive value of 100% to identify children at low risk for appendicitis, but with specificities ranging from 23% to 35%. The standard white blood cell (WBC) count achieved 100% sensitivity at a higher specificity than both novel biomarkers.

Conclusions:  Plasma calprotectin and serum/urine LRG are elevated in pediatric appendicitis. No individual marker performed as well as the WBC count.

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