Abstract
Background
Children who experience more than one urinary tract infection (UTI) are at increased risk of kidney scarring due to their UTIs. Girls are at especially high risk for developing kidney scarring as a result of recurrent UTIs. Prior work suggested that neutrophil gelatinase-associated lipocalin (NGAL) may be lower in children with recurrent UTI compared with those without. The objective of this work was to compare urine NGAL concentrations in matched urine samples in girls with single and recurrent UTIs.
Methods
Girls less than 6 years of age who presented with signs and symptoms of a UTI were eligible for enrollment. Both acute, obtained from residual urine collected as part of their clinical evaluation, and follow-up urine samples, obtained after the completion of antibiotics when the patient was in their usual state of health, were collected from patients. Acute and follow-up urine NGAL concentrations were compared between girls with single and recurrent UTIs, as well as those with negative cultures who served as controls.
Results
Seventy girls were included in this study, 6 controls, 43 single UTIs, and 20 girls with recurrent UTIs. Patients in the control group had lower median acute NGAL concentrations than either those with single or recurrent UTI. There were no differences in either acute or follow-up urine NGAL concentrations between those with single and recurrent UTIs.
Conclusion
In this cohort of girls less than 6 years of age, there is no difference in urine NGAL concentrations between those with single and recurrent UTIs.
Similar content being viewed by others
References
Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R (2007) Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA 298:179–186. https://doi.org/10.1001/jama.298.2.179
Shaikh N, Ewing AL, Bhatnagar S, Hoberman A (2010) Risk of renal scarring in children with a first urinary tract infection: a systematic review. Pediatrics 126:1084–1091. https://doi.org/10.1542/peds.2010-0685
Brandström P, Jodal U, Sillén U, Hansson S (2011) The Swedish reflux trial: review of a randomized, controlled trial in children with dilating vesicoureteral reflux. J Pediatr Urol 7:594–600. https://doi.org/10.1016/j.jpurol.2011.05.006
Shaikh N, Hoberman A, Keren R, Gotman N, Docimo SG, Mathews R, Bhatnagar S, Ivanova A, Mattoo TK, Moxey-Mims M, Carpenter MA, Pohl HG, Greenfield S (2016) Recurrent urinary tract infections in children with bladder and bowel dysfunction. Pediatrics 137:1–7. https://doi.org/10.1542/peds.2015-2982
Hewitt IK, Pennesi M, Morello W, Ronfani L, Montini G (2017) Antibiotic prophylaxis for urinary tract infection-related renal scarring: a systematic review. Pediatrics 139:e20163145. https://doi.org/10.1542/peds.2016-3145
Hoberman A, Greenfield SP, Mattoo TK, Keren R, Mathews R, Pohl HG, Kropp BP, Skoog SJ, Nelson CP, Moxey-Mims M, Chesney RW, Carpenter MA (2014) Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 370:2367–2376. https://doi.org/10.1056/NEJMoa1401811
Bachur R, Harper MB (2001) Reliability of the urinalysis for predicting urinary tract infections in young febrile children. Arch Pediatr Adolesc Med 155:60. https://doi.org/10.1001/archpedi.155.1.60
Shaikh N, Morone NE, Bost JE, Farrell MH (2008) Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J 27:302–308. https://doi.org/10.1097/INF.0b013e31815e4122
Uhari M, Nuutinen M (1988) Epidemiology of symptomatic infections of the urinary tract in children. BMJ 297:450–452. https://doi.org/10.1136/bmj.297.6646.450
Winberg J, Andersen HJ, Bergström T, Jacobsson B, Larson H, Lincoln K (1974) Epidemiology of symptomatic urinary tract infection in childhood. Acta Paediatr 63:1–20. https://doi.org/10.1111/j.1651-2227.1974.tb05718.x
Yeunug CK, Godley ML, Dhillon HK, Gordon I, Duffy PG, Ransley PG (1997) The characteristics of primary vesico-ureteric reflux in male and female infants with pre-natal hydronephrosis. Br J Urol 80:319–327. https://doi.org/10.1046/j.1464-410x.1997.00309.x
Wennerström M, Hansson S, Jodal U, Stokland E (2000) Primary and acquired renal scarring in boys and girls with urinary tract infection. J Pediatr 136:30–34. https://doi.org/10.1016/S0022-3476(00)90045-3
Zaki M, Badawi M, Al Mutari G, Ramadan D, Adul Rahman M (2005) Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study using 99mTc DMSA renal scintigraphy. Pediatr Nephrol 20:1116–1119. https://doi.org/10.1007/s00467-005-1880-2
Swerkersson S, Jodal U, Sixt R, Stokland E, Hansson S (2017) Urinary tract infection in small children: the evolution of renal damage over time. Pediatr Nephrol 32:1907–1913. https://doi.org/10.1007/s00467-017-3705-5
Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J (2007) Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 18:407–413. https://doi.org/10.1681/ASN.2006080882
Forster CS, Johnson K, Patel V, Wax R, Rodig N, Barasch J, Bachur R, Lee RS (2017) Urinary NGAL deficiency in recurrent urinary tract infections. Pediatr Nephrol 32:1077–1080. https://doi.org/10.1007/s00467-017-3607-6
Bennett MR, Nehus E, Haffner C, Ma Q, Devarajan P (2014) Pediatric reference ranges for acute kidney injury biomarkers. Pediatr Nephrol 30:677–685. https://doi.org/10.1007/s00467-014-2989-y
Roberts KB, Downs SM, Finell SME, Hellerstein S, Shortliffe LD, Wald ER, Zerin JM (2011) 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 128:595–610. https://doi.org/10.1542/peds.2011-1330
Team RC (2017) R: a language and environment for statistical computing. R Foundation for Stastitical Computing, Vienna, Austria. https://www.r-project.org
Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J-C, Müller M (2011) pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12:77. https://doi.org/10.1186/1471-2105-12-77
Paragas N, Kulkarni R, Werth M, Schmidt-Ott KM, Forster CS, Deng R, Zhang Q, Singer E, Klose AD, Shen TH, Francis KP, Ray S, Vijayakumar S, Seward S, Bovino ME, Xu K, Takabe Y, Amaral FE, Mohan S, Wax R, Corbin K, Sanna-Cherchi S, Mori K, Johnson L, Nickolas T, D’Agati V, Lin CS, Qiu A, Al-Awqati Q, Ratner AJ, Barasch J (2014) α-Intercalated cells defend the urinary system from bacterial infection. J Clin Invest 124:2963–2976. https://doi.org/10.1172/JCI71630
Steigedal M, Marstad A, Haug M, Damas JK, Strong RK, Roberts PL, Himpsl SD, Stapleton A, Hooton TM, Mobley HLT, Hawn TR, Flo TH (2014) Lipocalin 2 imparts selective pressure on bacterial growth in the bladder and is elevated in women with urinary tract infection. J Immunol 193:6081–6089. https://doi.org/10.4049/jimmunol.1401528
Price JR, Guran L, Lim JY, Megli CJ, Clark AL, Edwards SR, Denman MA, Gregory WT (2017) Neutrophil gelatinase–associated lipocalin biomarker and urinary tract infections. Female Pelvic Med Reconstr Surg 23:101–107. https://doi.org/10.1097/SPV.0000000000000366
Hatipoglu S, Sevketoglu E, Gedikbasi A, Yilmaz A, Kiyak A, Mulazimoglu M, Aydogan G, Ozpacaci T (2011) Urinary MMP-9/NGAL complex in children with acute cystitis. Pediatr Nephrol 26:1263–1268. https://doi.org/10.1007/s00467-011-1856-3
Forster CS, Jackson E, Ma Q, Bennett M, Shah SS, Goldstein SL (2018) Predictive ability of NGAL in identifying urinary tract infection in children with neurogenic bladders. Pediatr Nephrol 33:1365–1374. https://doi.org/10.1007/s00467-018-3936-0
Shaikh N, Hoberman A, Wise B, Kurs-Lasky M, Kearney D, Naylor S, Ann Haralam M, Colborn DK, Docimo SG (2003) Dysfunctional elimination syndrome: is it related to urinary tract infection or vesicoureteral reflux diagnosed early in life? Pediatrics 112:1134–1137. https://doi.org/10.1542/peds.112.5.1134
Saha D, Patel J, Buckingham D, Thornton D, Barber T, Watson JR (2017) Urine culture follow-up and antimicrobial stewardship in a pediatric urgent care network. Pediatrics 139:e20162103. https://doi.org/10.1542/peds.2016-2103
Arambašić J, Mandić S, Debeljak Z, Mandić D, Horvat V, Šerić V (2016) Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL). Clin Chem Lab Med 54:55–61. https://doi.org/10.1515/cclm-2015-0377
Acknowledgments
This work supported The Gerber Foundation. The funder did not have any role in either study design, data collection, interpretation, or analysis, the writing of this report, or the decision to submit this report for publication.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This work was approved by the Cincinnati Children’s Hospital Institutional Review Board. Written informed consent was obtained from parents or guardians for participation in this study. All data is available from the corresponding author upon reasonable request.
Conflicts of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Forster, C.S., Loechtenfeldt, A.M., Shah, S.S. et al. Urine neutrophil gelatinase-associated lipocalin in girls with recurrent urinary tract infections. Pediatr Nephrol 35, 2121–2128 (2020). https://doi.org/10.1007/s00467-020-04654-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-020-04654-9