Top

Pediatric Nephrology

Published in:

01-08-2018 | Original Article

Predictive ability of NGAL in identifying urinary tract infection in children with neurogenic bladders

Authors: Catherine S. Forster, Elizabeth Jackson, Qing Ma, Michael Bennett, Samir S. Shah, Stuart L. Goldstein

Published in: Pediatric Nephrology | Issue 8/2018

Abstract

Background

Distinguishing between urinary tract infection (UTI) and colonization (UTC) in patients with neurogenic bladders who require clean intermittent catheterization (CIC) is difficult. Urinary neutrophil gelatinase-associated lipocalin concentrations (uNGAL) are increased in UTIs. Our objective was to determine the predictive accuracy of uNGAL for UTI in CIC-dependent children.

Methods

Cross-sectional study of CIC-dependent patients from August, 2015 to November, 2016. UTI was defined as (1) growth of ≥ 50,000 cfu/mL of a uropathogen, (2) > 10 urinary white blood cells/hpf, and (3) ≥ 2 of the following: temperature > 38 °C, abdominal pain, back pain, worsened incontinence, pain with catheterization, or malodorous/cloudy urine. Positive urine cultures that did not meet these criteria were grouped as UTC, and negative cultures were grouped as no growth.

Results

Two hundred one patients were included (no growth = 100, UTC = 77, UTI = 24). Median (interquartile range) uNGAL was higher in the UTI group (UTI 1361 (931, 2516) μg/g creatinine, UTC 246 (106, 548) μg/g creatinine, no growth 36 (11, 179) μg/g creatinine, p < 0.01 for all comparisons). The area under the ROC curve for uNGAL for UTI versus no UTI was 0.89, 95% CI (0.80–0.98).

Conclusion

uNGAL is elevated in CIC-dependent children with UTI compared to those with negative cultures and those with UTC.

Dedeić-Ljubović A, Hukić M (2009) Catheter-related urinary tract infection in patients suffering from spinal cord injuries. Bosn J Basic Med Sci 9:2–9CrossRefPubMedPubMedCentral

Forster CS, Courter J, Jackson E, Mortensen J, Haslam D (2017) Frequency of multidrug-resistant organisms cultured from urine in children on clean intermittent catheterization. J Pediatric Infect Dis Soc 6:332–338PubMed

Lin J-N, Chen Y-H, Chang L-L, Lai C-H, Lin H-L, Lin H-H (2011) Clinical characteristics and outcomes of patients with extended-spectrum β-lactamase-producing bacteremias in the emergency department. Intern Emerg Med 6:547–555CrossRefPubMed

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 18:407–413CrossRefPubMed

Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A (2004) Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432:917–921CrossRefPubMed

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 26:1263–1268CrossRefPubMed

KDIGO AKI Work Group (2012) KDIGO clinical practice guidelines for acute kidney injury. Kidney Int Suppl 2:1–138CrossRef

Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee American College of Chest Physicians/Society of Critical Care Medicine Chest 101:1644–1655PubMed

Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarjan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMed

10.

Madden-Fuentes R, McNamara E (2013) Variation in definitions of urinary tract infections in spina bifida patients: a systematic review. Pediatrics 132:132–139CrossRefPubMed

11.

R: A language and environment for statistical computing (2013) Available from https://www.r-project.org/

12.

Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, Muller M (2011) pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12:77CrossRefPubMedPubMedCentral

13.

Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, Finkelstein JA, Gerber JS, Hyun DY, Linder JA, Lynfield R, Margolis DJ, May LS, Merenstein D, Metlay JP, Newlang JG, Piccirillo JF, Roberts RM, Sanchex GV, Suda KJ, Thomas A, Woo TM, Zetts RM, Hicks LA (2016) Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA 315:1864CrossRefPubMed

14.

Dotis J, Printza N, Marneri A, Gidaris D, Papachristou F (2013) Urinary tract infections caused by extended-spectrum beta- lactamase-producing bacteria in children : a matched case- control study. Turk J Paediatr 55:571–574

15.

Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management, Roberts KB (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 128:595–610CrossRef

16.

Vaidyanathan S, Soni BM, Dundas S, Krishnan KR (1994) Urethral cytology in spinal cord injury patients performing intermittent catheterisation. Paraplegia 32:493–500PubMed

17.

Schlager TA, Grady R, Mills SE, Hendley JO (2004) Bladder epithelium is abnormal in patients with neurogenic bladder due to myelomeningocele. Spinal Cord 42:163–168CrossRefPubMed

18.

Bachur R, Harper MB (2001) Reliability of the urinalysis for predicting urinary tract infections in young febrile children. Arch Pediatr Adolesc Med 155:60–65CrossRefPubMed

19.

Branson D (1966) Evaluaion of a rapid nitrate screening test for bacteriuria. Tech Bull Regist Med Technol 36:288–291PubMed

20.

Fouts DE, Pieper R, Szpakowski S, Pohl H, Knoblach S, Suh MJ, Huang ST, Sprague BM, Lucas SK, Torralba M, Nelson KE, Groah SL (2012) Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury. J Transl Med 10:174CrossRefPubMedPubMedCentral

21.

Powell H, McCredie D, Ritchie M (1987) Urinary nitrite in symptomatic and asymptomatic urinary infection. Arch Dis Child 62:138–140CrossRefPubMedPubMedCentral

22.

Schlager TA, Dilks S, Lohr J, Hayden GF, Kopco J, Hendley JW (1992) Periurethral colonization and urinary leukocytes as markers for bacteriuria in children with neurogenic bladder. Urol Res 20:361–363CrossRefPubMed

23.

Paragas N, Kulkarni R, Werth M, Schmidt-ott KM, Forster C, 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, Qui A, Al-Awqati Q, Ratner AJ, Barasch J (2014) The alpha-intercalated cell defends the urinary system from bacterial infection by excreting H+ and LNC2 in mouse and human urine. J Clin Invest 124:2963–2976CrossRefPubMedPubMedCentral

24.

Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 115:610–621CrossRefPubMedPubMedCentral

25.

Yilmaz A, Sevketoglu E, Gedikbasi A, Karyagar S, Kiyak A, Mulazimoglu M, Aydogan G, Ozpacaci T, Hatipoglu S (2009) Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatr Nephrol 24:2387–2392CrossRefPubMed

26.

Nielsen BS, Borregaard N, Bundgaard JR, Timshel S, Sehested M, Kjeldsen L (1996) Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases. Gut 38:414–420CrossRefPubMedPubMedCentral

27.

Sise ME, Forster C, Singer E, Sola-Del Valle D, Hahn B, Schmidt-Ott KM, Barasch J, Nickolas TL (2011) Urine neutrophil gelatinase-associated lipocalin identifies unilateral and bilateral urinary tract obstruction. Nephrol Dial Transplant 26:4132–4135CrossRefPubMedPubMedCentral

28.

Shiroyanagi Y, Suzuki M, Matsuno D, Yamazaki Y (2009) The significance of 99m technetium dimercapto-succinic acid renal scan in children with spina bifida during long-term follow up. J Urol 181:2262–2266CrossRefPubMed

29.

Parmaksız G, Noyan A, Dursun H, İnce E, Anarat R, Cengiz N (2016) Role of new biomarkers for predicting renal scarring in vesicoureteral reflux: NGAL, KIM-1, and L-FABP. Pediatr Nephrol 31:97–103CrossRefPubMed

30.

González Celedón C, Bitsori M, Tullus K (2007) Progression of chronic renal failure in children with dysplastic kidneys. Pediatr Nephrol 22:1014–1020CrossRefPubMed

31.

Nickolas TL, Forster CS, Sise ME, Barasch N, Valle DS-D, Viltard M, Buchen C, Kupferman S, Carnevali BM, Mattei S, Bovino A, Argentiero L, Magnano A, Devarajan P, Mori K, Erdjument-Bromage H, Tempst P, Allegri L, Barasch J (2012) NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease. Kidney Int 82:718–722CrossRefPubMedPubMedCentral

32.

Bennett MR, Nehus E, Haffner C, Ma Q, Devarajan P (2014) Pediatric reference ranges for acute kidney injury biomarkers. Pediatr Nephrol 30:677–685CrossRefPubMedPubMedCentral

Title: Predictive ability of NGAL in identifying urinary tract infection in children with neurogenic bladders
Authors: Catherine S. Forster
Elizabeth Jackson
Qing Ma
Michael Bennett
Samir S. Shah
Stuart L. Goldstein
Publication date: 01-08-2018
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 8/2018
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-018-3936-0

At a glance: The STEP trials

Springer Medicine

Predictive ability of NGAL in identifying urinary tract infection in children with neurogenic bladders

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 8/2018

Infections and the kidney: a tale from the tropics

Two rare cases of abdominal tumor in children: Answers

Genetic diagnosis of steroid-resistant nephrotic syndrome in a longitudinal collection of Czech and Slovak patients: a high proportion of causative variants in NUP93

Acquired thrombotic thrombocytopenic purpura with isolated CFHR3/1 deletion—rapid remission following complement blockade

Correction to: Effects of obesity and metabolic syndrome on cardiovascular outcomes in pediatric kidney transplant recipients: a longitudinal study

Metabolite diagnosis of primary hyperoxaluria type 3