Skip to main content

Advertisement

Log in

Urine neutrophil gelatinase-associated lipocalin in girls with recurrent urinary tract infections

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. 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

    Article  CAS  PubMed  Google Scholar 

  2. 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

    Article  PubMed  Google Scholar 

  3. 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

    Article  PubMed  Google Scholar 

  4. 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

    Article  Google Scholar 

  5. 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

    Article  PubMed  Google Scholar 

  6. 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

    Article  CAS  PubMed  Google Scholar 

  7. 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

    Article  CAS  PubMed  Google Scholar 

  8. 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

    Article  PubMed  Google Scholar 

  9. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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

    Article  Google Scholar 

  11. 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

    Article  Google Scholar 

  12. 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

    Article  PubMed  Google Scholar 

  13. 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

    Article  PubMed  Google Scholar 

  14. 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

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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

    Article  CAS  PubMed  Google Scholar 

  16. 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

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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

    Article  PubMed  PubMed Central  Google Scholar 

  18. 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

    Article  PubMed  Google Scholar 

  19. Team RC (2017) R: a language and environment for statistical computing. R Foundation for Stastitical Computing, Vienna, Austria. https://www.r-project.org

  20. 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

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 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

    Article  PubMed  Google Scholar 

  24. 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

    Article  PubMed  Google Scholar 

  25. 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

    Article  PubMed  PubMed Central  Google Scholar 

  26. 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

    Article  PubMed  Google Scholar 

  27. 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

    Article  PubMed  Google Scholar 

  28. 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

    Article  CAS  PubMed  Google Scholar 

Download references

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

Authors

Corresponding author

Correspondence to Catherine S. Forster.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-020-04654-9

Keywords

Navigation