Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL)
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Jadranka Arambašić
, Sanja Mandić, Željko Debeljak
, Dario Mandić , Vesna Horvat und Vatroslav Šerić
Abstract
Background: Acute pyelonephritis is a severe disease which is sometimes difficult to recognize based on clinical symptoms and routinely available diagnostic tests, especially in young children. The aim of this study was to assess the diagnostic value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a biomarker of acute pyelonephritis.
Methods: In this case-control study we analyzed 134 children (median age 2.5 years) who were admitted to the Pediatric Clinic of University Hospital Centre Osijek, Croatia. Eighty of them had acute pyelonephritis, while 54 children had febrile state of different etiology including cystitis and they represented the control group. uNGAL, white blood cells, C-reactive protein, urinanalysis, urine culture, kidney ultrasound and a dimercaptosuccinic acid scintigraphic scan were done for each child. uNGAL was measured using chemiluminiscent microparticle immunoassay on ARHITECT i1000SR (Abbott Diagnostics, IL, USA).
Results: uNGAL values were significantly higher in children with acute pyelonephritis compared to the control groups (113.6 ng/mL vs. 10.2 ng/mL, p<0.001). A receiver operating characteristic curve comparison was done for tested parameters and encouraging results were obtained for uNGAL (AUC=0.952). A cut-off value of 29.4 ng/mL had 92.5% sensitivity and 90.7% specificity. We showed that uNGAL can also serve in differentiating acute pyelonephritis from cystitis (cut-off 38.5 ng/mL), and for differentiation of cystitis from febrile states with etiology other than urinary tract infection (UTI) (cut-off 20.4 ng/mL).
Conclusions: uNGAL can be a useful diagnostic biomarker in acute pyelonephritis in children, but also in differentiating cystitis from febrile states other than UTI.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Lee H-E, Lee SH, Baek M, Choi H, Park K. Urinary measurement of neutrophil gelatinase associated lipocalin and kidney injury molecule-1 helps diagnose acute pyelonephritis in a preclinical model. J Biomarkers 2013. Article ID 413853, 6 pages, doi:10.1155/2013/413853.10.1155/2013/413853Suche in Google Scholar
2. Lippi G, Aloe R, Storelli A, Cervellin G, Trenti T. Evaluation of NGAL Test, a fully-automated neutrophil gelatinase-associated lipocalin (NGAL) immunoassay on Beckman Coulter AU 5822. Clin Chem Lab Med 2012;50:1581–4.10.1515/cclm.2011.839Suche in Google Scholar
3. Clerico A, Galli C, Fortunato A, Ronco C. Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences. Clin Chem Lab Med 2012;50:1505–17.10.1515/cclm-2011-0814Suche in Google Scholar
4. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 2002;10:1033–43.10.1016/S1097-2765(02)00708-6Suche in Google Scholar
5. Triebel S, Blaser J, Reinke H, Tschesche H. A 25 kDa alpha 2-microglobulin-related protein is a component of the 125 kDa form of human gelatinase. FEBS Lett 1992;314:386–8.10.1016/0014-5793(92)81511-JSuche in Google Scholar
6. Kjeldsen L, Johnsen AH, Sengelov H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem 1993;268:10425–32.10.1016/S0021-9258(18)82217-7Suche in Google Scholar
7. Devarajan P. Neutrophil gelatinase-associated lipocalin – an emerging troponin for kidney injury. Nephrol Dial Transplant 2008;23:3737–43.10.1093/ndt/gfn531Suche in Google Scholar PubMed PubMed Central
8. Makris K, Markou N, Evodia E, Dimopoulou E, Drakopoulos I, Ntetsika K, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med 2009;47:79–82.10.1515/CCLM.2009.004Suche in Google Scholar PubMed
9. Tomonaga Y, Szucs T, Ambuhl P, Nock S, Risch M, Risch L. Insights on urinary NGAL obtained in a primary care setting. Clin Chim Acta 2012;413:733–9.10.1016/j.cca.2012.01.001Suche in Google Scholar PubMed
10. Tong Z, Wu X, Ovcharenko D, Zhu J, Chen CS, Kehrer JP. Neutrophil gelatinase-associated lipocalin as a survival factor. Biochem J 2005;391:441–8.10.1042/BJ20051020Suche in Google Scholar PubMed PubMed Central
11. Grenier FC, Ali S, Syed H, Workman R, Martens F, Liao M, et al. Evaluation of the ARCHITECT urine NGAL assay: assay performance, specimen handling requirements and biological variability. Clin Biochem 2010;43:615–20.10.1016/j.clinbiochem.2009.12.008Suche in Google Scholar
12. Giaginis C, Zira A, Katsargyris A, Klonaris C, Theocharis S. Clinical implication of plasma neutrophil gelatinase-associated lipocalin (NGAL) concentrations in patients with advanced carotid atherosclerosis. Clin Chem Lab Med 2010;48:1035–41.10.1515/CCLM.2010.211Suche in Google Scholar
13. Devarajan P. Biomarkers for the early detection of acute kidney injury. Curr Opin Pediatr 2011;23:194–200.10.1097/MOP.0b013e328343f4ddSuche in Google Scholar
14. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics 1999;103:843–52.Suche in Google Scholar
15. Sanford JP, Favour CB, Mao FH, Harrison JH. Evaluation of the positive urine culture; an approach to the differentiation of significant bacteria from contaminants. Am J Med 1956;20:88–93.10.1016/0002-9343(56)90175-9Suche in Google Scholar
16. Seo WH, Nam SW, Lee EH, Je BK, Yim HE, Choi BM. A rapid plasma neutrophil gelatinase-associated lipocalin assay for diagnosis of acute pyelonephritis in infants with acute febrile urinary tract infections: a preliminary study. Eur J Pediatr 2014;173:229–32.10.1007/s00431-013-2112-6Suche in Google Scholar PubMed
17. Yilmaz A, Sevketoglu E, Gedikbasi A, Karyagar S, Kiyak A, Mulazimoglu M, et al. Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatr Nephrol 2009;24:2387–92.10.1007/s00467-009-1279-6Suche in Google Scholar PubMed
18. Dieter RS. Sterile pyuria: a differential diagnosis. Compr Ther 2000;26:150–2.10.1007/s12019-000-0001-1Suche in Google Scholar PubMed
19. Bhat RG, Katy TA, Place FC. Pediatric urinary tract infections. Emerg Med Clin North Am 2011;29:637–53.10.1016/j.emc.2011.04.004Suche in Google Scholar PubMed
20. Craig JC, Irwig LM, Howman-Giles RB, Uren RF, Bernard EJ, Knight JF, et al. Variability in the interpretation of dimercaptosuccinic acid scintigraphy after urinary tract infection in children. J Nucl Med 1998;39:1428–32.Suche in Google Scholar
21. Leroy S, Gervaix A. Procalcitonin: a key marker in children with urinary tract infection. Adv Urol 2011;2011:397618.10.1155/2011/397618Suche in Google Scholar PubMed PubMed Central
22. Sim JH, Yim HE, Choi BM, Lee JH, Yoo KH. Plasma neutrophil gelatinase-associated lipocalin predicts acute pyelonephritis in children with urinary tract infections. Pediatr Res. Advance online publication 15 April 2015; doi:10.1038/pr.2015.59.10.1038/pr.2015.59Suche in Google Scholar PubMed
23. Lippi G, Plebani M. Neutrophil gelatinase-associated lipocalin (NGAL): the laboratory perspective. Clin Chem Lab Med 2012;50:1483–7.10.1515/cclm-2012-0344Suche in Google Scholar PubMed
24. Makris K, Rizos D, Kafkas N, Haliassos A. Neutrophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine. Clin Chem Lab Med 2012;9:1519–32.Suche in Google Scholar
25. Cangemi G, Storti S, Cantinotti M, Fortunato A, Emdin M, Bruschettini M, et al. Reference values for urinary neutrophil gelatinase-associated lipocalin (NGAL) in pediatric age measured with a fully automated chemiluminescent platform. Clin Chem Lab Med 2013;51:1101–5.10.1515/cclm-2012-0540Suche in Google Scholar PubMed
©2016 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Editorial
- Building a bridge to safe diagnosis in health care. The role of the clinical laboratory
- Capillary electrophoresis for the screening and diagnosis of inherited hemoglobin disorders. Ready for prime time?
- Reviews
- Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: a systematic review and meta-analysis
- Towards biomarker-based tests that can facilitate decisions about prevention and management of preeclampsia in low-resource settings
- Mini Review
- Clinical relevance of sST2 in cardiac diseases
- General Clinical Chemistry and Laboratory Medicine
- Preservation of urine free catecholamines and their free O-methylated metabolites with citric acid as an alternative to hydrochloric acid for LC-MS/MS-based analyses
- Performance characteristics of the VIDAS® 25-OH Vitamin D Total assay – comparison with four immunoassays and two liquid chromatography-tandem mass spectrometry methods in a multicentric study
- Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL)
- Early postoperative C-terminal agrin fragment (CAF) serum levels predict graft loss and proteinuria in renal transplant recipients
- Homocitrulline: a new marker for differentiating acute from chronic renal failure
- Hematology and Coagulation
- Development of hemoglobin typing control materials for laboratory investigation of thalassemia and hemoglobinopathies
- Comparison of capillary electrophoresis and high performance liquid chromatography for detection and quantification of hemoglobin New York
- Prevalence of hemostatic alterations in patients with recurrent spontaneous subconjunctival hemorrhage
- Reference Values and Biological Variations
- Reference intervals for 24 laboratory parameters determined in 24-hour urine collections
- First trimester PAPP-A2, PAPP-A and hCGβ in small-for-gestational-age pregnancies
- Cancer Diagnostics
- Clinical utility of one versus two faecal immunochemical test samples in the detection of advanced colorectal neoplasia in symptomatic patients
- Cardiovascular Diseases
- Time from symptom onset influences high-sensitivity troponin T diagnostic accuracy for the diagnosis of acute myocardial infarction
- Prognostic significance of serum albumin level changes in acute ischemic stroke: the role of biological and analytical variation
- Correlates of serum hepcidin levels and its association with cardiovascular disease in an elderly general population
- Infectious Diseases
- Usefulness of several biomarkers in the management of septic patients: C-reactive protein, procalcitonin, presepsin and mid-regional pro-adrenomedullin
- Diabetes
- Performance of strip-based glucose meters and cassette-based blood gas analyzer for monitoring glucose levels in a surgical intensive care setting
- Accuracy and precision assessment of a new blood glucose monitoring system
- Acknowledgment
- Acknowledgment
- Letter to the Editors
- Glypican-1 as a highly sensitive and specific pancreatic cancer biomarker
- Platelet microRNAs are not modulated by systemic heparin in acute coronary syndromes
- Concomitant appearance of two false positive peaks with a true monoclonal one in a patient with plasma cell myeloma
- Anti-streptavidin interferences in Roche thyroid immunoassays: a case report
- Evaluation of the new Methotrexate CMIA assay on the Architect i2000SR
- Liposomal interference on Sysmex XN-series body fluid mode
- Development of an immunomagnetic beads-based test and its application in influenza surveillance
Artikel in diesem Heft
- Frontmatter
- Editorial
- Building a bridge to safe diagnosis in health care. The role of the clinical laboratory
- Capillary electrophoresis for the screening and diagnosis of inherited hemoglobin disorders. Ready for prime time?
- Reviews
- Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: a systematic review and meta-analysis
- Towards biomarker-based tests that can facilitate decisions about prevention and management of preeclampsia in low-resource settings
- Mini Review
- Clinical relevance of sST2 in cardiac diseases
- General Clinical Chemistry and Laboratory Medicine
- Preservation of urine free catecholamines and their free O-methylated metabolites with citric acid as an alternative to hydrochloric acid for LC-MS/MS-based analyses
- Performance characteristics of the VIDAS® 25-OH Vitamin D Total assay – comparison with four immunoassays and two liquid chromatography-tandem mass spectrometry methods in a multicentric study
- Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL)
- Early postoperative C-terminal agrin fragment (CAF) serum levels predict graft loss and proteinuria in renal transplant recipients
- Homocitrulline: a new marker for differentiating acute from chronic renal failure
- Hematology and Coagulation
- Development of hemoglobin typing control materials for laboratory investigation of thalassemia and hemoglobinopathies
- Comparison of capillary electrophoresis and high performance liquid chromatography for detection and quantification of hemoglobin New York
- Prevalence of hemostatic alterations in patients with recurrent spontaneous subconjunctival hemorrhage
- Reference Values and Biological Variations
- Reference intervals for 24 laboratory parameters determined in 24-hour urine collections
- First trimester PAPP-A2, PAPP-A and hCGβ in small-for-gestational-age pregnancies
- Cancer Diagnostics
- Clinical utility of one versus two faecal immunochemical test samples in the detection of advanced colorectal neoplasia in symptomatic patients
- Cardiovascular Diseases
- Time from symptom onset influences high-sensitivity troponin T diagnostic accuracy for the diagnosis of acute myocardial infarction
- Prognostic significance of serum albumin level changes in acute ischemic stroke: the role of biological and analytical variation
- Correlates of serum hepcidin levels and its association with cardiovascular disease in an elderly general population
- Infectious Diseases
- Usefulness of several biomarkers in the management of septic patients: C-reactive protein, procalcitonin, presepsin and mid-regional pro-adrenomedullin
- Diabetes
- Performance of strip-based glucose meters and cassette-based blood gas analyzer for monitoring glucose levels in a surgical intensive care setting
- Accuracy and precision assessment of a new blood glucose monitoring system
- Acknowledgment
- Acknowledgment
- Letter to the Editors
- Glypican-1 as a highly sensitive and specific pancreatic cancer biomarker
- Platelet microRNAs are not modulated by systemic heparin in acute coronary syndromes
- Concomitant appearance of two false positive peaks with a true monoclonal one in a patient with plasma cell myeloma
- Anti-streptavidin interferences in Roche thyroid immunoassays: a case report
- Evaluation of the new Methotrexate CMIA assay on the Architect i2000SR
- Liposomal interference on Sysmex XN-series body fluid mode
- Development of an immunomagnetic beads-based test and its application in influenza surveillance