Skip to main content
Top
Published in: Pediatric Nephrology 2/2020

01-02-2020 | Urinary Tract Infection | Original Article

Biomarkers that differentiate false positive urinalyses from true urinary tract infection

Authors: Nader Shaikh, Judith M. Martin, Alejandro Hoberman, Megan Skae, Linette Milkovich, Christi McElheny, Robert W. Hickey, Lucine V. Gabriel, Diana H. Kearney, Massoud Majd, Eglal Shalaby-Rana, George Tseng, Jay Kolls, William Horne, Zhiguang Huo, Timothy R. Shope

Published in: Pediatric Nephrology | Issue 2/2020

Login to get access

Abstract

Background

The specificity of the leukocyte esterase test (87%) is suboptimal. The objective of this study was to identify more specific screening tests that could reduce the number of children who unnecessarily receive antimicrobials to treat a presumed urinary tract infection (UTI).

Methods

Prospective cross-sectional study to compare inflammatory proteins in blood and urine samples collected at the time of a presumptive diagnosis of UTI. We also evaluated serum RNA expression in a subset.

Results

We enrolled 200 children; of these, 89 were later demonstrated not to have a UTI based on the results of the urine culture obtained. Urinary proteins that best discriminated between children with UTI and no UTI were involved in T cell response proliferation (IL-9, IL-2), chemoattractants (CXCL12, CXCL1, CXCL8), the cytokine/interferon pathway (IL-13, IL-2, INFγ), or involved in innate immunity (NGAL). The predictive power (as measured by the area under the curve) of a combination of four urinary markers (IL-2, IL-9, IL-8, and NGAL) was 0.94. Genes in the pathways related to inflammation were also upregulated in serum of children with UTI.

Conclusions

Urinary proteins involved in the inflammatory response may be useful in identifying children with false positive results with current screening tests for UTI; this may reduce unnecessary treatment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Williams GJ, Macaskill P, Chan SF, Turner RM, Hodson E, Craig JC (2010) Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis. Lancet Infect Dis 10:240–250PubMed Williams GJ, Macaskill P, Chan SF, Turner RM, Hodson E, Craig JC (2010) Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis. Lancet Infect Dis 10:240–250PubMed
2.
go back to reference Shaikh N, Hoberman A, Hum SW, Alberty A, Muniz G, Kurs-Lasky M, Landsittel D, Shope T (2018) Development and Validation of a Calculator for Estimating the Probability of Urinary Tract Infection in Young Febrile Children. JAMA Pediatr 172:550–556PubMedPubMedCentral Shaikh N, Hoberman A, Hum SW, Alberty A, Muniz G, Kurs-Lasky M, Landsittel D, Shope T (2018) Development and Validation of a Calculator for Estimating the Probability of Urinary Tract Infection in Young Febrile Children. JAMA Pediatr 172:550–556PubMedPubMedCentral
3.
go back to reference Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I (2001) Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125:279–284PubMed Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I (2001) Controlling the false discovery rate in behavior genetics research. Behav Brain Res 125:279–284PubMed
4.
go back to reference Breiman L, Friedman JH, Olshen RA, Stone CJ (1984) Classification and regression trees. Wadsworth, Inc., Monterey Breiman L, Friedman JH, Olshen RA, Stone CJ (1984) Classification and regression trees. Wadsworth, Inc., Monterey
5.
go back to reference Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14:R36PubMedPubMedCentral Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14:R36PubMedPubMedCentral
6.
go back to reference Stone AF, Mendall MA, Kaski JC, Edger TM, Risley P, Poloniecki J, Camm AJ, Northfield TC (2002) Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA). Circulation 106:1219–1223PubMed Stone AF, Mendall MA, Kaski JC, Edger TM, Risley P, Poloniecki J, Camm AJ, Northfield TC (2002) Effect of treatment for Chlamydia pneumoniae and Helicobacter pylori on markers of inflammation and cardiac events in patients with acute coronary syndromes: South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA). Circulation 106:1219–1223PubMed
7.
go back to reference Chaussabel D, Quinn C, Shen J, Patel P, Glaser C, Baldwin N, Stichweh D, Blankenship D, Li L, Munagala I, Bennett L, Allantaz F, Mejias A, Ardura M, Kaizer E, Monnet L, Allman W, Randall H, Johnson D, Lanier A, Punaro M, Wittkowski KM, White P, Fay J, Klintmalm G, Ramilo O, Palucka AK, Banchereau J, Pascual V (2008) A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity 29:150–164PubMedPubMedCentral Chaussabel D, Quinn C, Shen J, Patel P, Glaser C, Baldwin N, Stichweh D, Blankenship D, Li L, Munagala I, Bennett L, Allantaz F, Mejias A, Ardura M, Kaizer E, Monnet L, Allman W, Randall H, Johnson D, Lanier A, Punaro M, Wittkowski KM, White P, Fay J, Klintmalm G, Ramilo O, Palucka AK, Banchereau J, Pascual V (2008) A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity 29:150–164PubMedPubMedCentral
8.
go back to reference Watson JR, Hains DS, Cohen DM, Spencer JD, Kline JM, Yin H, Schwaderer AL (2016) Evaluation of novel urinary tract infection biomarkers in children. Pediatr Res 79:934–939PubMedPubMedCentral Watson JR, Hains DS, Cohen DM, Spencer JD, Kline JM, Yin H, Schwaderer AL (2016) Evaluation of novel urinary tract infection biomarkers in children. Pediatr Res 79:934–939PubMedPubMedCentral
9.
go back to reference Shaikh N, Morone NE, Bost JE, Farrell MH (2008) Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J 27:302–308PubMed Shaikh N, Morone NE, Bost JE, Farrell MH (2008) Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J 27:302–308PubMed
10.
go back to reference Noelle RJ, Nowak EC (2010) Cellular sources and immune functions of interleukin-9. Nat Rev Immunol 10:683–687PubMed Noelle RJ, Nowak EC (2010) Cellular sources and immune functions of interleukin-9. Nat Rev Immunol 10:683–687PubMed
11.
go back to reference Sundac L, Dando SJ, Sullivan MJ, Derrington P, Gerrard J, Ulett GC (2016) Protein-based profiling of the immune response to uropathogenic Escherichia coli in adult patients immediately following hospital admission for acute cystitis. Pathog Dis 74(6). doi: https://doi.org/10.1093/femspd/ftw062 PubMed Sundac L, Dando SJ, Sullivan MJ, Derrington P, Gerrard J, Ulett GC (2016) Protein-based profiling of the immune response to uropathogenic Escherichia coli in adult patients immediately following hospital admission for acute cystitis. Pathog Dis 74(6). doi: https://​doi.​org/​10.​1093/​femspd/​ftw062 PubMed
12.
go back to reference Liao W, Lin JX, Leonard WJ (2011) IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol 23:598–604PubMedPubMedCentral Liao W, Lin JX, Leonard WJ (2011) IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol 23:598–604PubMedPubMedCentral
13.
14.
go back to reference Girard D, Gosselin J, Heitz D, Paquin R, Beaulieu AD (1995) Effects of interleukin-2 on gene expression in human neutrophils. Blood 86:1170–1176PubMed Girard D, Gosselin J, Heitz D, Paquin R, Beaulieu AD (1995) Effects of interleukin-2 on gene expression in human neutrophils. Blood 86:1170–1176PubMed
16.
go back to reference Ko YC, Mukaida N, Ishiyama S, Tokue A, Kawai T, Matsushima K, Kasahara T (1993) Elevated interleukin-8 levels in the urine of patients with urinary tract infections. Infect Immun 61:1307–1314PubMedPubMedCentral Ko YC, Mukaida N, Ishiyama S, Tokue A, Kawai T, Matsushima K, Kasahara T (1993) Elevated interleukin-8 levels in the urine of patients with urinary tract infections. Infect Immun 61:1307–1314PubMedPubMedCentral
17.
go back to reference Krzemien G, Szmigielska A, Turczyn A, Panczyk-Tomaszewska M (2016) Urine interleukin-6, interleukin-8 and transforming growth factor beta1 in infants with urinary tract infection and asymptomatic bacteriuria. Cent Eur J Immunol 41:260–267PubMedPubMedCentral Krzemien G, Szmigielska A, Turczyn A, Panczyk-Tomaszewska M (2016) Urine interleukin-6, interleukin-8 and transforming growth factor beta1 in infants with urinary tract infection and asymptomatic bacteriuria. Cent Eur J Immunol 41:260–267PubMedPubMedCentral
18.
go back to reference 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, Qiu A, Al-Awqati Q, Ratner AJ, Barasch J (2014) alpha-Intercalated cells defend the urinary system from bacterial infection. J Clin Invest 124:2963–2976PubMedPubMedCentral 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, Qiu A, Al-Awqati Q, Ratner AJ, Barasch J (2014) alpha-Intercalated cells defend the urinary system from bacterial infection. J Clin Invest 124:2963–2976PubMedPubMedCentral
19.
go back to reference Agarwal I, Iswarya J, Flemming J, Chaturvedi S, Mathew LG, Varkey SD, Sahni RD (2013) Prospective study to determine the usefulness of urinary neutrophil gelatinase associated lipocalin(NAGL) as an early and sensitive marker of urinary tract infection (UTI) in children. Pediatr Nephrol 28:1358 Agarwal I, Iswarya J, Flemming J, Chaturvedi S, Mathew LG, Varkey SD, Sahni RD (2013) Prospective study to determine the usefulness of urinary neutrophil gelatinase associated lipocalin(NAGL) as an early and sensitive marker of urinary tract infection (UTI) in children. Pediatr Nephrol 28:1358
20.
go back to reference Jung N, Byun HJ, Park JH, Kim JS, Kim HW, Ha JY (2018) Diagnostic accuracy of urinary biomarkers in infants younger than 3 months with urinary tract infection. Korean J Pediatr 61:24–29PubMedPubMedCentral Jung N, Byun HJ, Park JH, Kim JS, Kim HW, Ha JY (2018) Diagnostic accuracy of urinary biomarkers in infants younger than 3 months with urinary tract infection. Korean J Pediatr 61:24–29PubMedPubMedCentral
21.
go back to reference Lee HE, Kim DK, Kang HK, Park K (2015) The diagnosis of febrile urinary tract infection in children may be facilitated by urinary biomarkers. Pediatr Nephrol 30:123–130PubMed Lee HE, Kim DK, Kang HK, Park K (2015) The diagnosis of febrile urinary tract infection in children may be facilitated by urinary biomarkers. Pediatr Nephrol 30:123–130PubMed
23.
go back to reference Valdimarsson S, Jodal U, Barregard L, Hansson S (2017) Urine neutrophil gelatinase-associated lipocalin and other biomarkers in infants with urinary tract infection and in febrile controls. Pediatr Nephrol 32:2079–2087PubMed Valdimarsson S, Jodal U, Barregard L, Hansson S (2017) Urine neutrophil gelatinase-associated lipocalin and other biomarkers in infants with urinary tract infection and in febrile controls. Pediatr Nephrol 32:2079–2087PubMed
24.
go back to reference Almeida RP, Vanet A, Witko-Sarsat V, Melchior M, McCabe D, Gabay JE (1996) Azurocidin, a natural antibiotic from human neutrophils: expression, antimicrobial activity, and secretion. Protein Expr Purif 7:355–366PubMed Almeida RP, Vanet A, Witko-Sarsat V, Melchior M, McCabe D, Gabay JE (1996) Azurocidin, a natural antibiotic from human neutrophils: expression, antimicrobial activity, and secretion. Protein Expr Purif 7:355–366PubMed
25.
go back to reference Korotkova N, Yarova-Yarovaya Y, Tchesnokova V, Yazvenko N, Carl MA, Stapleton AE, Moseley SL (2008) Escherichia coli DraE adhesin-associated bacterial internalization by epithelial cells is promoted independently by decay-accelerating factor and carcinoembryonic antigen-related cell adhesion molecule binding and does not require the DraD invasin. Infect Immun 76:3869–3880PubMedPubMedCentral Korotkova N, Yarova-Yarovaya Y, Tchesnokova V, Yazvenko N, Carl MA, Stapleton AE, Moseley SL (2008) Escherichia coli DraE adhesin-associated bacterial internalization by epithelial cells is promoted independently by decay-accelerating factor and carcinoembryonic antigen-related cell adhesion molecule binding and does not require the DraD invasin. Infect Immun 76:3869–3880PubMedPubMedCentral
26.
go back to reference Muenzner P, Kengmo Tchoupa A, Klauser B, Brunner T, Putze J, Dobrindt U, Hauck CR (2016) Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa. PLoS Pathog 12:e1005608PubMedPubMedCentral Muenzner P, Kengmo Tchoupa A, Klauser B, Brunner T, Putze J, Dobrindt U, Hauck CR (2016) Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa. PLoS Pathog 12:e1005608PubMedPubMedCentral
27.
go back to reference Arao S, Matsuura S, Nonomura M, Miki K, Kabasawa K, Nakanishi H (1999) Measurement of urinary lactoferrin as a marker of urinary tract infection. J Clin Microbiol 37:553–557PubMedPubMedCentral Arao S, Matsuura S, Nonomura M, Miki K, Kabasawa K, Nakanishi H (1999) Measurement of urinary lactoferrin as a marker of urinary tract infection. J Clin Microbiol 37:553–557PubMedPubMedCentral
28.
go back to reference Pan Y, Sonn GA, Sin ML, Mach KE, Shih MC, Gau V, Wong PK, Liao JC (2010) Electrochemical immunosensor detection of urinary lactoferrin in clinical samples for urinary tract infection diagnosis. Biosens Bioelectron 26:649–654PubMedPubMedCentral Pan Y, Sonn GA, Sin ML, Mach KE, Shih MC, Gau V, Wong PK, Liao JC (2010) Electrochemical immunosensor detection of urinary lactoferrin in clinical samples for urinary tract infection diagnosis. Biosens Bioelectron 26:649–654PubMedPubMedCentral
29.
go back to reference Yu Y, Zielinski MD, Rolfe MA, Kuntz MM, Nelson H, Nelson KE, Pieper R (2015) Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria. Infect Immun 83:4142–4153PubMedPubMedCentral Yu Y, Zielinski MD, Rolfe MA, Kuntz MM, Nelson H, Nelson KE, Pieper R (2015) Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria. Infect Immun 83:4142–4153PubMedPubMedCentral
30.
go back to reference Kjolvmark C, Pahlman LI, Akesson P, Linder A (2014) Heparin-binding protein: a diagnostic biomarker of urinary tract infection in adults. Open Forum Infect Dis 1:ofu004PubMedPubMedCentral Kjolvmark C, Pahlman LI, Akesson P, Linder A (2014) Heparin-binding protein: a diagnostic biomarker of urinary tract infection in adults. Open Forum Infect Dis 1:ofu004PubMedPubMedCentral
31.
go back to reference Schwaderer AL, Wang H, Kim S, Kline JM, Liang D, Brophy PD, McHugh KM, Tseng GC, Saxena V, Barr-Beare E, Pierce KR, Shaikh N, Manak JR, Cohen DM, Becknell B, Spencer JD, Baker PB, Yu CY, Hains DS (2016) Polymorphisms in alpha-Defensin-Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral Reflux. J Am Soc Nephrol 27:3175–3186PubMedPubMedCentral Schwaderer AL, Wang H, Kim S, Kline JM, Liang D, Brophy PD, McHugh KM, Tseng GC, Saxena V, Barr-Beare E, Pierce KR, Shaikh N, Manak JR, Cohen DM, Becknell B, Spencer JD, Baker PB, Yu CY, Hains DS (2016) Polymorphisms in alpha-Defensin-Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral Reflux. J Am Soc Nephrol 27:3175–3186PubMedPubMedCentral
32.
go back to reference Chromek M, Slamova Z, Bergman P, Kovacs L, Podracka L, Ehren I, Hokfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A (2006) The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 12:636–641PubMed Chromek M, Slamova Z, Bergman P, Kovacs L, Podracka L, Ehren I, Hokfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A (2006) The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 12:636–641PubMed
33.
go back to reference Babikir IH, Abugroun EA, Bilal NE, Alghasham AA, Abdalla EE, Adam I (2018) The impact of cathelicidin, the human antimicrobial peptide LL-37 in urinary tract infections. BMC Infect Dis 18:17PubMedPubMedCentral Babikir IH, Abugroun EA, Bilal NE, Alghasham AA, Abdalla EE, Adam I (2018) The impact of cathelicidin, the human antimicrobial peptide LL-37 in urinary tract infections. BMC Infect Dis 18:17PubMedPubMedCentral
34.
go back to reference Nielsen KL, Dynesen P, Larsen P, Jakobsen L, Andersen PS, Frimodt-Moller N (2014) Role of urinary cathelicidin LL-37 and human beta-defensin 1 in uncomplicated Escherichia coli urinary tract infections. Infect Immun 82:1572–1578PubMedPubMedCentral Nielsen KL, Dynesen P, Larsen P, Jakobsen L, Andersen PS, Frimodt-Moller N (2014) Role of urinary cathelicidin LL-37 and human beta-defensin 1 in uncomplicated Escherichia coli urinary tract infections. Infect Immun 82:1572–1578PubMedPubMedCentral
35.
go back to reference Godaly G, Proudfoot AE, Offord RE, Svanborg C, Agace WW (1997) Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration. Infect Immun 65:3451–3456PubMedPubMedCentral Godaly G, Proudfoot AE, Offord RE, Svanborg C, Agace WW (1997) Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration. Infect Immun 65:3451–3456PubMedPubMedCentral
36.
go back to reference Hordijk PL (2016) Recent insights into endothelial control of leukocyte extravasation. Cell Mol Life Sci 73:1591–1608PubMed Hordijk PL (2016) Recent insights into endothelial control of leukocyte extravasation. Cell Mol Life Sci 73:1591–1608PubMed
37.
go back to reference Koskinen K, Vainio PJ, Smith DJ, Pihlavisto M, Yla-Herttuala S, Jalkanen S, Salmi M (2004) Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1). Blood 103:3388–3395PubMed Koskinen K, Vainio PJ, Smith DJ, Pihlavisto M, Yla-Herttuala S, Jalkanen S, Salmi M (2004) Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1). Blood 103:3388–3395PubMed
38.
go back to reference Watzl C, Long EO (2010) Signal transduction during activation and inhibition of natural killer cells. Curr Protoc Immunol Chapter 11:Unit 11 19B Watzl C, Long EO (2010) Signal transduction during activation and inhibition of natural killer cells. Curr Protoc Immunol Chapter 11:Unit 11 19B
39.
go back to reference Gur C, Coppenhagen-Glazer S, Rosenberg S, Yamin R, Enk J, Glasner A, Bar-On Y, Fleissig O, Naor R, Abed J, Mevorach D, Granot Z, Bachrach G, Mandelboim O (2013) Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells. Cell Host Microbe 14:664–674PubMed Gur C, Coppenhagen-Glazer S, Rosenberg S, Yamin R, Enk J, Glasner A, Bar-On Y, Fleissig O, Naor R, Abed J, Mevorach D, Granot Z, Bachrach G, Mandelboim O (2013) Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of NK cells. Cell Host Microbe 14:664–674PubMed
40.
go back to reference Isaacson B, Hadad T, Glasner A, Gur C, Granot Z, Bachrach G, Mandelboim O (2017) Stromal Cell-Derived Factor 1 Mediates Immune Cell Attraction upon Urinary Tract Infection. Cell Rep 20:40–47PubMed Isaacson B, Hadad T, Glasner A, Gur C, Granot Z, Bachrach G, Mandelboim O (2017) Stromal Cell-Derived Factor 1 Mediates Immune Cell Attraction upon Urinary Tract Infection. Cell Rep 20:40–47PubMed
41.
go back to reference Benson M, Jodal U, Andreasson A, Karlsson A, Rydberg J, Svanborg C (1994) Interleukin 6 response to urinary tract infection in childhood. Pediatr Infect Dis J 13:612–616PubMed Benson M, Jodal U, Andreasson A, Karlsson A, Rydberg J, Svanborg C (1994) Interleukin 6 response to urinary tract infection in childhood. Pediatr Infect Dis J 13:612–616PubMed
42.
go back to reference Su H, Lei CT, Zhang C (2017) Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front Immunol 8:405PubMedPubMedCentral Su H, Lei CT, Zhang C (2017) Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front Immunol 8:405PubMedPubMedCentral
43.
go back to reference Hannan TJ, Mysorekar IU, Hung CS, Isaacson-Schmid ML, Hultgren SJ (2010) Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection. PLoS Pathog 6:e1001042PubMedPubMedCentral Hannan TJ, Mysorekar IU, Hung CS, Isaacson-Schmid ML, Hultgren SJ (2010) Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection. PLoS Pathog 6:e1001042PubMedPubMedCentral
44.
go back to reference Fleischmann JD, Wentworth DB, Thomas KM, Imbembo AL (1989) Urinary interleukin-2 inhibition in patients with cystitis. Immunol Investig 18:825–831 Fleischmann JD, Wentworth DB, Thomas KM, Imbembo AL (1989) Urinary interleukin-2 inhibition in patients with cystitis. Immunol Investig 18:825–831
Metadata
Title
Biomarkers that differentiate false positive urinalyses from true urinary tract infection
Authors
Nader Shaikh
Judith M. Martin
Alejandro Hoberman
Megan Skae
Linette Milkovich
Christi McElheny
Robert W. Hickey
Lucine V. Gabriel
Diana H. Kearney
Massoud Majd
Eglal Shalaby-Rana
George Tseng
Jay Kolls
William Horne
Zhiguang Huo
Timothy R. Shope
Publication date
01-02-2020
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 2/2020
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-019-04403-7

Other articles of this Issue 2/2020

Pediatric Nephrology 2/2020 Go to the issue