Novel Serum and Urine Markers for Pediatric Appendicitis

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.