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Discriminatory Precision of Neutrophil Gelatinase-Associated Lipocalin in Detection of Urinary Tract Infection in Children: a Systematic Review and Meta-Analysis

Arash Abbasi, Fardin Nabizadeh, Maryam Gardeh, Kosar Mohamed Ali, Mahmoud Yousefifard, Mostafa Hosseini



Introduction: There is a significant discrepancy between studies on diagnostic precision of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis of urinary tract infection (UTI). Therefore, the present systematic review and meta-analysis was designed to assess the diagnostic value of NGAL in diagnosis of UTI in children and adolescents.

Methods: An extensive search was performed on Medline, Embase, Scopus and Web of Science databases by the end of 2019. Two independent researchers screened and summarized the data. Discriminatory precision of urinary and serum NGAL was assessed by reporting area under the curve, sensitivity, specificity and diagnostic odds ratio with 95% confidence interval (95% CI).

Results: Data from 12 studies were included. The area under the curve of urinary and serum NGAL for diagnosis of UTI in children and adolescents at the best cut-off point (between 30-39.9 ng/ml) was 0.95 (95% CI: 0.93 to 0.97) and 0.83 (95% CI: 0.80 to 0.86), respectively. Sensitivity, specificity and diagnostic odds ratio on urinary NGAL at these cut-off points were 0.89 (95% CI: 0.64 to 0.97), 0.89 (95% CI: 0.71 to 0.97) and 67 (95% CI: 5 to 891), respectively. Sensitivity, specificity and diagnostic odds ratio of serum NGAL in UTI detection were 0.85 (95% CI: 0.70 to 0.90), 0.81 (95% CI: 0.69 to 0.88) and 9.53 (95% CI: 1.52 to 59.65), respectively.

Conclusion: The present meta-analysis showed that urinary NGAL had a high diagnostic value in detection of UTI in children and adolescents with an optimum cut-off point in the range of 30-39.9 ng/ml.


Lipocalin-2; Urinary Tract Infections; Child; Predictive Value of Tests


Sastre JBL, Aparicio AR, Cotallo GDC, Colomer BF, Hernández MC, de Hospitales Castrillo G. Urinary tract infection in the newborn: clinical and radio imaging studies. Pediatric Nephrology. 2007;22(10):1735-41.

Mårild S, Jodal U. Incidence rate of first‐time symptomatic urinary tract infection in children under 6 years of age. Acta Paediatrica. 1998;87(5):549-52.

Schappert S, Rechtsteiner E. Ambulatory medical care utilization estimates for 2007. Vital and Health Statistics Series 13, Data from the National Health Survey. 2011(169):1-38.

Mangiarotti P, Pizzini C, Fanos V. Antibiotic prophylaxis in children with relapsing urinary tract infections: review. Journal of chemotherapy. 2000;12(2):115-23.

DAS R, Ahmed T, Saha H, Shahrin L, Afroze F, SHAHID A, et al. Clinical risk factors, bacterial aetiology, and outcome of urinary tract infection in children hospitalized with diarrhoea in Bangladesh. Epidemiology & Infection. 2016:1-7.

Shaikh N, Mattoo TK, Keren R, Ivanova A, Cui G, Moxey-Mims M, et al. Early antibiotic treatment for pediatric febrile urinary tract infection and renal scarring. JAMA pediatrics. 2016;170(9):848-54.

Roberts KB. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595-610.

Jacobson SH, Eklöf O, Eriksson CG, Lins L-E, Tidgren B, Winberg J. Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up. Bmj. 1989;299(6701):703-6.

Izadi A, Yousefifard M, Nakhjavan-Shahraki B, Baikpour M, Mirzay Razaz J, Hosseini M. Diagnostic value of Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) in detection of pediatric acute kidney injury; a systematic review and meta-analysis. International Journal of Pediatrics. 2016;4(11):3875-95.

Izadi A, Yousefifard M, Nakhjavan-Shahraki B, Baikpour M, Mirzay Razaz J, Ataei N, et al. Value of plasma/serum neutrophil gelatinase-associated lipocalin in detection of pediatric acute kidney injury; a systematic review and meta-analysis. International Journal of Pediatrics. 2016;4(11):3815-36.

Valdimarsson S, Jodal U, Barregård L, Hansson S. Urine neutrophil gelatinase-associated lipocalin and other biomarkers in infants with urinary tract infection and in febrile controls. Pediatric Nephrology. 2017;32(11):2079-87.

Lee H-E, Kim DK, Kang HK, Park K. The diagnosis of febrile urinary tract infection in children may be facilitated by urinary biomarkers. Pediatric Nephrology. 2015;30(1):123-30.

Kitao T, Kimata T, Yamanouchi S, Kato S, Tsuji S, Kaneko K. Urinary biomarkers for screening for renal scarring in children with febrile urinary tract infection: pilot study. The Journal of urology. 2015;194(3):766-71.

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. Jama. 2000;283(15):2008-12.

Yousefifard M, Movaghar VR, Baikpour M, Ghelichkhani P, Hosseini M, Jafari AM, et al. Early versus Late Decompression for Traumatic Spinal Cord Injuries; a Systematic Review and Meta-analysis. Emergency. 2017;5(1):e37.

Yousefifard M, Baikpour M, Ghelichkhani P, Asady H, Nia KS, Jafari AM, et al. Screening Performance Characteristic of Ultrasonography and Radiography in Detection of Pleural Effusion; a Meta-Analysis. Emergency. 2016;4(1):1-10.

Ghelichkhani P, Yousefifard M, Nazemi L, Safari S, Hosseini M, Baikpour M, et al. The Value of Serum Β-Subunit of Human Chorionic Gonadotropin Level in Prediction of Treatment Response to Methotrexate in Management of Ectopic Pregnancy; a Systematic Review and Meta-Analysis. International Journal of Pediatrics. 2016;4(9):3503-18.

Ebrahimi A, Yousefifard M, Kazemi HM, Rasouli HR, Asady H, Jafari AM, et al. Diagnostic accuracy of chest ultrasonography versus chest radiography for identification of pneumothorax: a systematic review and meta-analysis. Tanaffos. 2014;13(4):29-40.

Safari S, Yousefifard M, Hashemi B, Baratloo A, Forouzanfar MM, Rahmati F, et al. The value of serum creatine kinase in predicting the risk of rhabdomyolysis-induced acute kidney injury: a systematic review and meta-analysis. Clinical and experimental nephrology. 2016;20(2):153-61.

Rahimi-Movaghar V, Yousefifard M, Ghelichkhani P, Baikpour M, Tafakhori A, Asady H, et al. Application of Ultrasonography and Radiography in Detection of Hemothorax: a Systematic Review and Meta-Analysis. EMERGENCY-An Academic Emergency Medicine Journal. 2016;4(3):116-26.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine. 2009;151(4):264-9.

Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Annals of internal medicine. 2011;155(8):529-36.

Forster CS, Jackson E, Ma Q, Bennett M, Shah SS, Goldstein SL. Predictive ability of NGAL in identifying urinary tract infection in children with neurogenic bladders. Pediatric nephrology (Berlin, Germany). 2018;33(8):1365-74.

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 journal of nephrology. 2019;29(5):340-4.

Jung N, Byun HJ, Park JH, Kim JS, Kim HW, Ha JY. Diagnostic accuracy of urinary biomarkers in infants younger than 3 months with urinary tract infection. Korean journal of pediatrics. 2018;61(1):24-9.

Kim BH, Yu N, Kim HR, Yun KW, Lim IS, Kim TH, et al. Evaluation of the optimal neutrophil gelatinase-associated lipocalin value as a screening biomarker for urinary tract infections in children. Annals of laboratory medicine. 2014;34(5):354-9.

Krzemien G, Panczyk-Tomaszewska M, Adamczuk D, Kotula I, Demkow U, Szmigielska A. Neutrophil Gelatinase-Associated Lipocalin: A Biomarker for Early Diagnosis of Urinary Tract Infections in Infants. Advances in experimental medicine and biology. 2018;1047:71-80.

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(6):e20171090.

Nickavar A, Safaeian B, Valavi E, Moradpour F. Validity of Neutrophil Gelatinase Associated Lipocaline as a Biomarker for Diagnosis of Children with Acute Pyelonephritis. Urology journal. 2016;13(5):2860-3.

Safdar OY, Shalaby MA, Toffaha WM, Turki AA, Toffaha WM, Ghunaim AH, et al. Neutrophil gelatinase-associated lipocalin as an early marker for the diagnosis of urinary tract infections in Saudi children. Journal of Nephrology & Therapeutics. 2015;5(6):1-4.

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. European journal of pediatrics. 2014;173(2):229-32.

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. Pediatric nephrology (Berlin, Germany). 2009;24(12):2387-92.

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. Pediatric nephrology (Berlin, Germany). 2014;29(11):2181-9.

Lin L. Comparison of four heterogeneity measures for meta-analysis. Journal of Evaluation in Clinical Practice. 2020;26(1):376-84.

Forster CS, Johnson K, Patel V, Wax R, Rodig N, Barasch J, et al. Urinary NGAL deficiency in recurrent urinary tract infections. Pediatric nephrology (Berlin, Germany). 2017;32(6):1077-80.

Shaw AD, Chalfin DB, Kleintjens J. The economic impact and cost-effectiveness of urinary neutrophil gelatinase-associated lipocalin after cardiac surgery. Clinical therapeutics. 2011;33(11):1713-25.

Parikh A, Rizzo JA, Canetta P, Forster C, Sise M, Maarouf O, et al. Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis. PLoS One. 2017;12(5):e0178091.

DOI: https://doi.org/10.22037/aaem.v8i1.597

DOI (PDF): https://doi.org/10.22037/aaem.v8i1.597.g795

DOI (HTML): https://doi.org/10.22037/aaem.v8i1.597.g808