Urinary biomarkers in pediatric appendicitis

Purpose: The diagnosis of pediatric appendicitis is still a challenge, resulting in perforation and negative appendectomies. The aim of this study was to evaluate novel biomarkers in urine and to use the most promising biomarkers in conjunction with the Pediatric Appendicitis Score (PAS), to see whether this could improve the accuracy of diagnosing appendicitis. Methods: A prospective study of children with suspected appendicitis was conducted with assessment of PAS, routine blood tests, and measurements of four novel urinary biomarkers: leucine-rich α-2-glycoprotein (LRG), calprotectin, interleukin 6 (IL-6), and substance P. The biomarkers were blindly determined with commercial ELISAs. Urine creatinine was used to adjust for dehydration. The diagnosis of appendicitis was based on histopathological analysis. Results: Forty-four children with suspected appendicitis were included, of which twenty-two (50 %) had confirmed appendicitis. LRG in urine was elevated in children with appendicitis compared to children without (p <0.001), and was higher in children with gangrenous and perforated appendicitis compared to those with phlegmonous appendicitis (p = 0.003). No statistical significances between groups were found for calprotectin, IL-6 or substance P. LRG had a receiver operating characteristic area under the curve of 0.86 (95 % CI 0.79–0.99), and a better diagnostic performance than all routine blood tests. LRG in conjunction with PAS showed 95 % sensitivity, 90 % specificity, 91 % positive predictive value, and 95 % negative predictive value. Conclusion: LRG, adjusted for dehydration, is a promising novel urinary biomarker for appendicitis in children. LRG in combination with PAS has a high diagnostic performance