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Association of Neutrophil Gelatinase associated Lipocalin and Leukocyte Differential Count in Children with Febrile Urinary Tract Infections

  • Jang, Ji Won (Department of Pediatrics, Korea University College of Medicine) ;
  • Yim, Hyung Eun (Department of Pediatrics, Korea University College of Medicine) ;
  • Yoo, Kee Hwan (Department of Pediatrics, Korea University College of Medicine)
  • Received : 2020.06.16
  • Accepted : 2020.09.21
  • Published : 2020.10.31

Abstract

Purpose: To investigate the association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and leukocyte differential count in children with urinary tract infections (UTIs). Methods: A retrospective chart review was performed in children undergoing uNGAL measurements between June 2018 and September 2019. Patients with suspected or diagnosed UTIs were included. The relationship between uNGAL and blood leukocyte differential count was investigated in children. Results: A total of 197 children were included in this study, 119 of whom (60%) had UTIs. The non-UTI patients (n=78) were diagnosed with pneumonia, acute gastroenteritis, viral upper respiratory infection, and others. After adjusting for age, gender, and fever duration, the leukocyte count, monocyte count, and uNGAL levels were higher in the UTI group than in the non-UTI group (P<0.05). uNGAL showed positive correlations with neutrophil counts, monocyte counts, the neutrophil-to-lymphocyte ratio, and the monocyte-to-lymphocyte ratio in the UTI group (P<0.05). uNGAL levels were only associated with the neutrophil-to-lymphocyte ratio in the non-UTI group (P<0.05). In a multivariable logistic regression analysis, only uNGAL was associated with the presence of UTI (P<0.05). The area under the receiver operating characteristic curves for uNGAL and monocyte counts to identify UTI were 0.89 (95% confidence interval (CI): 0.824-0.939; P=0.025) and 0.7 (95% CI: 0.627-0.774; P=0.038), respectively. Conclusions: In children with UTIs, uNGAL levels may be associated with blood leukocyte differential counts. uNGAL measurements and monocyte counts can be helpful in children with suspected UTIs.

Keywords

References

  1. Lee SJ. Clinical guideline for childhood urinary tract infection (second revision). Child Kidney Dis 2015;19:56-64. https://doi.org/10.3339/chikd.2015.19.2.56
  2. Strohmeier Y, Hodson EM, Willis NS, Webster AC, Craig JC. Antibiotics for acute pyelonephritis in children. Cochrane Database Syst Rev, 2014;28;CD003772.
  3. National Collaborating Centre for Women's and Children's Health. Urinary Tract Infection in Children: Diagnosis, Treatment and Long Term Management. London, England: RCOG Press; 2007.
  4. Han SY, Lee IR, Park SJ, Kim JH, Shin JI. Usefulness of neutrophillymphocyte ratio in young children with febrile urinary tract infection. Korean J Pediatr 2016;59:139-44. https://doi.org/10.3345/kjp.2016.59.3.139
  5. Tullus K. Difficulties in diagnosing urinary tract infections in small children. Pediatr Nephrol 2011;26:1923-6. https://doi.org/10.1007/s00467-011-1966-y
  6. Tullus K. Low urinary bacterial counts: do they count? Pediatr Nephrol 2016;31:171-4. https://doi.org/10.1007/s00467-015-3227-y
  7. Masajtis-Zagajewska A, Nowicki M. New markers of urinary tract infection. Clinica Chimica Acta 2017;471:286-91. https://doi.org/10.1016/j.cca.2017.06.003
  8. Yim HE. Neutrophil gelatinase-associated lipocalin and kidney diseases. Child Kidney Dis 2015;19:79-88. https://doi.org/10.3339/chikd.2015.19.2.79
  9. Ichino M, Kuroyanagi Y, Kusaka M, Mori T, Ishikawa K, Shiroki R, et al. Increased urinary neutrophil gelatinase associated lipocalin levels in a rat model of upper urinary tract infection. J Urol 2009;181:2326-31. https://doi.org/10.1016/j.juro.2009.01.010
  10. Fjaertoft G, Foucard T, Xu S, Venge P. Human neutrophil lipocalin (HNL) as a diagnostic tool in children with acute infections: a study of the kinetics. Acta Paediatr 2005;94:661-6. https://doi.org/10.1111/j.1651-2227.2005.tb01961.x
  11. Lubell TR, Barasch JM, Xu K, Ieni M, Cabrera KI, Dayan PS. Urinary neutrophil gelatinase-associated lipocalin for the diagnosis of urinary tract infections. Pediatrics 2017;140:e20171090. https://doi.org/10.1542/peds.2017-1090
  12. Skowron B, Baranowska A, Dobrek L, Ciesielczyk K, Kaszuba-Zwoinska J, Wiecek G, et al. Urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, uromodulin, and cystatin C concentrations in an experimental rat model of ascending acute kidney injury induced by pyelonephritis. J Physiol Pharmacol 2018;69:625-37.
  13. Naess A, Nilssen SS, Mo R, Eide GE, Sjursen H. Role of neutrophil to lymphocyte and monocyte to lymphocyte ratios in the diagnosis of bacterial infection in patients with fever. Infection 2017;45:299-307. https://doi.org/10.1007/s15010-016-0972-1
  14. Loonen AJ, de Jager CP, Tosserams J, Kusters R, Hilbink M, Wever PC, et al. Biomarkers and molecular analysis to improve blood stream infection diagnostics in an emergency care unit. PloS One 2014;9:e87315. https://doi.org/10.1371/journal.pone.0087315
  15. Riley LK, Rupert J. Evaluation of patients with leukocytosis. AM Fam Phys 2015;92:1004-11.
  16. Terradas R, Grau S, Blanch J, Riu M, Saballs P, Castells X, et al. Eosinophil count and neutrophil-lymphocyte count ratio as prognostic markers in patients with bacteremia: a retrospective cohort study. PloS One 2012;7:e42860. https://doi.org/10.1371/journal.pone.0042860
  17. Meshaal MS, Nagi A, Eldamaty A, Gaber M, Rizk HJTEHJ. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as independent predictors of outcome in infective endocarditis (IE). Egypt Heart J 2019;71:13. https://doi.org/10.1186/s43044-019-0014-2
  18. Serbina NV, Hohl TM, Cherny M, Pamer EG. Selective expansion of the monocytic lineage directed by bacterial infection. J Immunol 2009;183:1900-10. https://doi.org/10.4049/jimmunol.0900612
  19. Dixit A, Bottek J, Beerlage AL, Schuettpelz J, Thiebes S, Brenzel A, et al. Frontline science: proliferation of Ly6C(+) monocytes during urinary tract infections is regulated by IL-6 trans-signaling. J Leukoc Biol 2018;103:13-22.
  20. Ingersoll MA, Platt AM, Potteaux S, Randolph GJ. Monocyte trafficking in acute and chronic inflammation. Trends Immunol 2011;32:470-7. https://doi.org/10.1016/j.it.2011.05.001
  21. Abraham SN, Miao Y. The nature of immune responses to urinary tract infections. Nat Rev Immunol 2015;15:655-63. https://doi.org/10.1038/nri3887
  22. Bieber K, Autenrieth SE. Insights how monocytes and dendritic cells contribute and regulate immune defense against microbial pathogens. Immunobiology 2015;220:215-26. https://doi.org/10.1016/j.imbio.2014.10.025
  23. Perez RP, Ortega MJC, Alvarez JA, Baquero-Artigao F, Rico JCS, Zuniga RV, et al. Recommendations on the diagnosis and treatment of urinary tract infection]. Anales de Pediatria 2019;90:400.e1-9.
  24. Krzeminska E, Wyczalkowska-Tomasik A, Korytowska N, Paczek L. Paczek comparison of two methods for determination of NGAL levels in urine: ELISA and CMIA. J Clin Lab Anal 2016;30:956-60. https://doi.org/10.1002/jcla.21962
  25. Lowsby R, Gomes C, Jarman I, Lisboa P, Nee PA, Vardhan M, et al. Neutrophil to lymphocyte count ratio as an early indicator of blood stream infection in the emergency department. Emerg Med J 2015;32:531-4. https://doi.org/10.1136/emermed-2014-204071
  26. Turak O, Ozcan F, Isleyen A, Basar FN, Gul M, Yilmaz S, et al. Usefulness of neutrophil-to-lymphocyte ratio to predict in-hospital outcomes in infective endocarditis. Can J Cardiol 2013;29:1672-8. https://doi.org/10.1016/j.cjca.2013.05.005
  27. de Jager CP, van Wijk PTL, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC. Lymphocytopenia and neutrophillymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 2010;14:R192-R20021034463.
  28. Wyllie DH, Bowler ICJW, Peto TEA. Relation between lymphopenia and bacteraemia in UK adults with medical emergencies. J Clin Pathol 2004;57:950-5. https://doi.org/10.1136/jcp.2004.017335
  29. Wang Jl, Lu Xy, Xu Xh, Zhang Kj, Gong H, Lv D, et al. Predictive role of monocyte-to-lymphocyte ratio in patients with Klebsiella pneumonia infection: a single-center experience. Medicine (Baltimore) 2019;98:e17215. https://doi.org/10.1097/MD.0000000000017215
  30. Djordjevic D, Rondovic G, Surbatovic M, Stanojevic I, Udovicic I, Andjelic T, et al. Neutrophil-to-lymphocyte ratio, monocyte-tolymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume-to-platelet count ratio as biomarkers in critically ill and injured patients: which ratio to choose to predict outcome and nature of bacteremia?. Mediators Inflamm 2018;15:2018:3758068.
  31. Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nature Immunol 2006;7:311-7.. https://doi.org/10.1038/ni1309
  32. Duell BL, Carey AJ, Dando SJ, Schembri MA, Ulett GC. Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to uropathogenic Escherichia coli. PLoS ONE 2013;8:e78013. https://doi.org/10.1371/journal.pone.0078013
  33. Cai L, Rubin J, Han W, Venge P, Xu S. The origin of multiple molecular forms in urine of HNL/NGAL. Clin J Am Soc Nephrol 2010;5:2229-35. https://doi.org/10.2215/CJN.00980110
  34. Yim HE, Yim H, Bae ES, Woo SU, Yoo KH. Predictive value of urinary and serum biomarkers in young children with febrile urinary tract infections. Pediatr Nephrol 2014;29:2181-9. https://doi.org/10.1007/s00467-014-2845-0
  35. Jagadesan I, Agarwal I, Chaturvedi S, Jose A, Sahni RD, Fleming JJ. Urinary neutrophil gelatinase associated lipocalin - a sensitive marker for urinary tract infection in children. Indian J Nephrol 2019;29:340-4. https://doi.org/10.4103/ijn.IJN_276_18
  36. Zarkesh M, Sedaghat F, Heidarzadeh A, Tabrizi M, Moghadam KB, Ghesmati S. Diagnostic Value of IL-6, CRP, WBC, and Absolute Neutrophil Count to Predict Serious Bacterial Infection in Febrile Infants. Acta Medica Iranica 2015;53.
  37. Sproston NR, Ashworth JJ. Ashworth Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018;9:754. https://doi.org/10.3389/fimmu.2018.00754
  38. Shaikh S, Salim E, Ram PV, Memon SS, Zubairi A, Khawaja SA, et al. Correlation of C-reactive protein and total leukocyte count in acute infections. Pak J Surg 2019;35:271-4.
  39. Forster CS, Devarajan P. Neutrophil gelatinase-associated lipocalin: utility in urologic conditions. Pediatric Nephrology 2017;32:377-81. https://doi.org/10.1007/s00467-016-3540-0