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Meta-Analysis
. 2020 Sep 10;9(9):CD009185.
doi: 10.1002/14651858.CD009185.pub3.

Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the diagnosis of acute pyelonephritis in children

Kai J Shaikh  1 , Victor A Osio  2 , Mariska Mg Leeflang  3 , Nader Shaikh  4
Affiliations
Meta-Analysis

Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the diagnosis of acute pyelonephritis in children

Kai J Shaikh et al. Cochrane Database Syst Rev. .

Abstract

Background: In children with urinary tract infection (UTI), only those with pyelonephritis (and not cystitis) are at risk for developing long-term renal sequelae. If non-invasive biomarkers could accurately differentiate children with cystitis from children with pyelonephritis, treatment and follow-up could potentially be individualized. This is an update of a review first published in 2015.

Objectives: The objectives of this review were to 1) determine whether procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic evaluation of children with UTI; 2) assess the influence of patient and study characteristics on the diagnostic accuracy of these tests, and 3) compare the performance of the three tests to each other.

Search methods: We searched MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews through to 17th December 2019 for this review. The reference lists of all included articles and relevant systematic reviews were searched to identify additional studies not found through the electronic search.

Selection criteria: We only considered published studies that evaluated the results of an index test (PCT, CRP, ESR) against the results of an acute-phase 99Tc-dimercaptosuccinic acid (DMSA) scan (conducted within 30 days of the UTI) in children aged 0 to 18 years with a culture-confirmed episode of UTI. The following cut-off values were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP and 30 mm/hour for ESR.

Data collection and analysis: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate pooled random-effects pooled sensitivity and specificity values.

Main results: A total of 36 studies met our inclusion criteria. Twenty-five studies provided data for the primary analysis: 12 studies (1000 children) included data on PCT, 16 studies (1895 children) included data on CRP, and eight studies (1910 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the PCT, CRP, ESR tests at the aforementioned cut-offs were 0.81 (0.67 to 0.90), 0.93 (0.86 to 0.96), and 0.83 (0.71 to 0.91), respectively. The summary specificity values for PCT, CRP, and ESR tests at these cut-offs were 0.76 (0.66 to 0.84), 0.37 (0.24 to 0.53), and 0.57 (0.41 to 0.72), respectively.

Authors' conclusions: The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

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Conflict of interest statement

  1. Kai J Shaikh: none known

  2. Victor A Osio: none known

  3. Nader Shaikh: none known

  4. Mariska MG Leeflang: none known

Figures

1
1
Study flow diagram
CRP ‐ C‐reactive protein; DMSA ‐ 99Tc‐dimercaptosuccinic acid; ESR ‐ erythrocyte sedimentation rate; PCT ‐ procalcitonin; SPECT ‐ single‐photon emission computed tomography
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study
3
3
Summary ROC plot of procalcitonin > 0.5 ng/mL (solid point = pooled accuracy; dotted oval = 95% confidence region)
1
1. Test
PCT > 0.5 ng/mL
4
4
Forest plot of PCT at cut‐offs other than 0.5 ng/mL
5
5
Summary ROC plot of C‐reactive protein > 20 mg/L (solid point = pooled accuracy; dotted oval = 95% confidence region)
2
2. Test
CRP > 20 mg/L
6
6
Forest plot of CRP at cut‐offs other than 20 mg/L
7
7
Summary ROC plot of erythrocyte sedimentation rate ≥ 30 mm/hr (solid point = pooled accuracy; dotted oval = 95% confidence region)
3
3. Test
ESR ≥ 30 mm/hour
8
8
Forest plot of erythrocyte sedimentation rate at cut‐offs other than 30 mm/hr
9
9
Direct comparison of C‐reactive protein > 20 mg/L and procalcitonin > 0.5 ng/mL
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References

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Eremeeva 2016 {published data only}
    1. Eremeeva A, Dlin V, Korsunsky A, Orekhova S, Bondarenko E, Gurbanova S. Lipocalin-2 associated with neutrophilic gelatinases (uNGAL) as the marker of microbial inflammatory diseases of kidneys and urinary tract in children [abstract]. Pediatric Nephrology 2016;31(10):1767-8. [EMBASE: 612479409]
Fang 2017 {published data only}
    1. Fang J, Luan J, Zhu GH, Qi C, Wang D. Detection of PCT and urinary beta2 -MG enhances the accuracy for localization diagnosing pediatric urinary tract infection. Journal of Clinical Laboratory Analysis 2017;31(5):e22088. [MEDLINE: ] - PMC - PubMed
Fang 2020 {published data only}
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Fernandez 2001 {published data only}
    1. Fernandez Lopez A, Luaces Cubells C, Valls Tolosa C, Ortega Rodriguez J, Garcia Garcia J J, Mira Vallet A, et al. Procalcitonin in the early diagnosis of invasive bacterial infection in febrile infants [Procalcitonina para el diagnostico precoz de infeccion bacteriana invasiva en el lactante febril]. Anales Espanoles de Pediatria 2001;55(4):321-8. [MEDLINE: ] - PubMed
Fernandez 2003 {published data only}
    1. Fernandez Lopez A, Luaces Cubells C, Garcia Garcia JJ, Fernandez Pou J, Spanish Society of Pediatric Emergencies. Procalcitonin in pediatric emergency departments for the early diagnosis of invasive bacterial infections in febrile infants: results of a multicenter study and utility of a rapid qualitative test for this marker. Pediatric Infectious Disease Journal 2003;22(10):895-903. [MEDLINE: ] - PubMed
Fernandez‐Menendez 2003 {published data only}
    1. Fernandez-Menendez JM, Malaga S, Matesanz JL, Solis G, Alonso S, Perez-Mendez C. Risk factors in the development of early technetium-99m dimercaptosuccinic acid renal scintigraphy lesions during first urinary tract infection in children. Acta Paediatrica 2003;92(1):21-6. [MEDLINE: ] - PubMed
Figueiredo 1999 {published data only}
    1. Figueiredo S, Rocha P, Coelho E, Alexandrino AM, Rocha H. Retrospective study of urinary tract infection in infants [Estudo retrospectivo de infeccao urinaria alta em lactentes]. Nascer e Crescer 1999;8(2):89-92. [EMBASE: 1999270461]
Friedman‐Gruszczynska 2008 {published data only}
    1. Friedman-Gruszczynska J. Assessment of clinical relevance of CRP levels in infectious diseases in children [Ocena przydatnosci klinicznej oznaczania stezenia bialka CRP w chorobach infekcyjnych u dziec]. Pediatria Polska 2008;83(1):49-53. [EMBASE: 2008097172]
Galetto‐Lacour 2002 {published data only}
    1. Galetto-Lacour A, Zamora S, Gervaix A. Blood markers of severe bacterial infections [abstract]. In: 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; Sep 27-30 2002; San Diego, USA. 2002.
Galetto‐Lacour 2003 {published data only}
    1. Galetto-Lacour A, Zamora SA, Gervaix A. Bedside procalcitonin and C-reactive protein tests in children with fever without localizing signs of infection seen in a referral center. Pediatrics 2003;112(5):1054-60. [MEDLINE: ] - PubMed
Garcia de Guadiana 2011 {published and unpublished data}
    1. Garcia de Guadiana L, Gonzalez J, Gonzalez M, Martin E, Albaladejo M, Cortes P. Usefulness of C-reactive protein in admission to localize site of urinary infection in children [abstract]. Clinical Chemistry & Laboratory Medicine 2011;49(Suppl 1):S637. [EMBASE: 70517512]
Gendrel 1998 {published data only}
    1. Gendrel D. Urinary tract infection and biological markers: C-reactive protein, interleukins and procalcitonin [Infection urinaire biologiques: proteine C reactive, interleukine et procalcitonine]. Archives de Pediatrie 1998;5 Suppl 3:269-73S. [MEDLINE: ] - PubMed
Gervaix 2001 {published data only}
    1. Gervaix A, Galetto-Lacour A, Gueron T, Vadas L, Zamora S, Suter S, et al. Usefulness of procalcitonin and C-reactive protein rapid tests for the management of children with urinary tract infection. Pediatric Infectious Disease Journal 2001;20(5):507-11. [MEDLINE: ] - PubMed
Ghasemi 2013 {published data only}
    1. Ghasemi K, Montazeri S, Pashazadeh AM, Javadi H, Assadi M. Correlation of 99mTc-DMSA scan with radiological and laboratory examinations in childhood acute pyelonephritis: a time-series study [abstract]. European Journal of Nuclear Medicine & Molecular Imaging 2013;40(Suppl 2):S279. [DOI: ] - PubMed
Ghasemi 2016 {published data only}
    1. Ghasemi K, Esteghamati M, Borzoo S, Parvaneh E. Predictive accuracy of urinary neutrophil gelatinase associated lipocalin (NGAL) for renal parenchymal involvement in children with acute pyelonephritis. Electron Physician [Electronic Resource] 2016;8(2):1911-7. [MEDLINE: ] - PMC - PubMed
Girardin 2000 {published data only}
    1. Girardin E. Pyelonephritis in children: new tools for evaluation [Pyelonephrites de l'enfant: nouveaux moyens d'evaluation]. Medecine Therapeutique Pediatrie 2000;3(5):376-80. [EMBASE: 30944096]
Giunta 2014 {published data only}
    1. Giunta F, Forfori F, Seri G. Molecular markers for urinary tract infections. Official Gazette of the United States Patent & Trademark Office Patents 2014. [US Patent US 2013/0084650 A1 ]
Grouteau 1999 {published data only}
    1. Grouteau E, Fauvel J, Blum G, Ouhayoun E, Salles J, Decramer S, et al. Phospholipase A2 (Pla2) and C reactive protein (CRP) in acute pyelonephritis in children. Correlation with DMSA scan [abstract no: P92]. Pediatric Nephrology 1999;13.
Guermazi 1993 {published data only}
    1. Guermazi F, Lenoir P, Verboven M, Smets A, Braeckman J, Jonckheer M, et al. Technetium 99m labeled dimercaptosuccinic acid (99m Tc-DMSA) scintigraphy in the diagnosis and follow-up of urinary infections in children [Apport de la scintigraphie a l'acide dimercaptosuccinque marque au technetium 99m (99mTC-DSA) dans le diagnostic et le suivi des infections urinaires de l'enfant]. Archives Francaises de Pediatrie 1993;50(5):391-8. [MEDLINE: ] - PubMed
Gurgoze 2005 {published data only}
    1. Gurgoze M, Akarsu S, Yilmaz E, Godekmerdan A, Akca Z, Ciftci I, et al. Proinflammatory cytokines and procalcitonin in children with acute pyelonephritis. Pediatric Nephrology 2005;20(10):1445-8. [MEDLINE: ] - PubMed
Guven 2006 {published data only}
    1. Guven AG, Kazdal HZ, Koyun M, Aydn F, Gungor F, Akman S, et al. Accurate diagnosis of acute pyelonephritis: How helpful is procalcitonin? Nuclear Medicine Communications 2006;27(9):715-21. [MEDLINE: ] - PubMed
Hahn 2003 {published data only}
    1. Hahn H, Moon DH, Yang YJ, Park YS. Renal scarring after acute pyelonephritis in children under the age of 5 years is primarily related to the extent and severity of acute inflammatory changes [abstract]. Journal of Nuclear Medicine 2003;44(5 Suppl):358. [BIOSIS Previews: PREV200300383499]
Han 2016 {published data only}
    1. Han SY, Lee IR, Park SJ, Kim JH, Shin JI. Usefulness of neutrophil-lymphocyte ratio in young children with febrile urinary tract infection. Korean Journal of Pediatrics 2016;49(3):139-44. [MEDLINE: ] - PMC - PubMed
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Hellerstein 1981 {published data only}
    1. Hellerstein S, Duggan E, Welchert E, Mansour F. Localization of the site or urinary tract infections using serum C reactive protein [abstract]. Pediatric Research 1981;15(4 Pt 2):694. [DOI: 10.1203/00006450-198104001-01528] [BIOSIS Previews: PREV198121026875] - DOI
Hellerstein 1982 {published data only}
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Hewitt 2008 {published data only}
    1. Hewitt IK, Zucchetta P, Rigon L, Maschio F, Molinari PP, Tomasi L, et al. Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials. Pediatrics 2008;122(3):486-90. [MEDLINE: ] - PubMed
Hitzel 2002 {published data only}
    1. Hitzel A, Liard A, Vera P, Manrique A, Menard JF, Dacher JN. Color and power Doppler sonography versus DMSA scintigraphy in acute pyelonephritis and in prediction of renal scarring. Journal of Nuclear Medicine 2002;43(1):27-32. [MEDLINE: ] - PubMed
Hsu 2016 {published data only}
    1. Hsu CC, Tsai JD, Ku MS, Chen SM, Liao PF, Hung TW, et al. Antimicrobial resistance and diagnostic imaging in infants younger than 2 months old hospitalized with a first febrile urinary tract infection: a population-based comparative study. Pediatric Infectious Disease Journal 2016;35(8):840-5. [MEDLINE: ] - PubMed
Huang 2007 {published data only}
    1. Huang DT, Huang FY, Tsai TC, Tsai JD, Chiu NC, Lin CC. Clinical differentiation of acute pyelonephritis from lower urinary tract infection in children. Journal of Microbiology, Immunology & Infection 2007;40(6):513-7. [MEDLINE: ] - PubMed
Hubert‐Dibon 2018 {published data only}
    1. Hubert-Dibon G, Danjou L, Feildel-Fournial C, Vrignaud B, Masson D, Launay E, et al. Procalcitonin and C-reactive protein may help to detect invasive bacterial infections in children who have fever without source. Acta Paediatrica 2018;107(7):1262-9. [MEDLINE: ] - PubMed
Ilyas 2002 {published data only}
    1. Ilyas M, Mastin ST, Richard GA. Age-related radiological imaging in children with acute pyelonephritis. Pediatric Nephrology 2002;17(1):30-4. [MEDLINE: ] - PubMed
Jakobsson 1992a {published data only}
    1. Jakobsson B, Söderlundh S, Berg U. Diagnostic significance of 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy in urinary tract infection. Archives of Disease in Childhood 1992;67(11):1338-42. [MEDLINE: ] - PMC - PubMed
Jakobsson 1992b {published data only}
    1. Jakobsson B, Nolstedt L, Svensson L, Soderlundh S, Berg U. 99mTechnetium-dimercaptosuccinic acid scan in the diagnosis of acute pyelonephritis in children: relation to clinical and radiological findings. Pediatric Nephrology 1992;6(4):328-34. [MEDLINE: ] - PubMed
Jakobsson 1994 {published data only}
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Jakobsson 1997 {published data only}
    1. Jakobsson B, Svensson L. Transient pyelonephritic changes on 99mTechnetium-dimercaptosuccinic acid scan for at least five months after infection. Acta Paediatrica 1997;86(8):806-7. [MEDLINE: ] - PubMed
Jaksic 2011 {published data only}
    1. Jaksic E, Bogdanovic R, Artiko V, Saranovic DS, Petrasinovic Z, Petrovic M, et al. Diagnostic role of initial renal cortical scintigraphy in children with the first episode of acute pyelonephritis. Annals of Nuclear Medicine 2011;25(1):37-43. [MEDLINE: ] - PubMed
Jantausch 1994 {published data only}
    1. Jantausch BA, Rifai N, Getson P, Akram S, Majd M, Wiedermann BL. Urinary N-acetyl-beta-glucosaminidase and beta-2-microglobulin in the diagnosis of urinary tract infection in febrile infants. Pediatric Infectious Disease Journal 1994;13(4):294-9. [MEDLINE: ] - PubMed
Jodal 1975 {published data only}
    1. Jodal U, Lindberg U, Lincoln K. Level diagnosis of symptomatic urinary tract infections in childhood. Acta Paediatrica Scandinavica 1975;64(2):201-8. [MEDLINE: ] - PubMed
Johnson 1985 {published data only}
    1. Johnson CE, Shurin PA, Marchant CD, Strieter CM, Murdell-Panek D, Debaz BP, et al. Identification of children requiring radiologic evaluation for urinary infection. Pediatric Infectious Disease 1985;46(6):656-63. [MEDLINE: ] - PubMed
Kanellopoulos 2005 {published data only}
    1. Kanellopoulos TA, Vassilakos PJ, Kantzis M, Ellina A, Kolonitsiou F, Papanastasiou DA. Low bacterial count urinary tract infections in infants and young children. European Journal of Pediatrics 2005;164(6):355-61. [MEDLINE: ] - PubMed
Kangari 2015 {published data only}
    1. Kangari G, Esteghamati M, Ghasemi K, Mahboobi H. Predictive accuracy of urinary beta2-microglobulin for kidney injury in children with acute pyelonephritis. Iranian Journal of Kidney Diseases 2015;9(1):19-24. [MEDLINE: ] - PubMed
Karakatsani 1997 {published data only}
    1. Karakatsani Z, Kipuru C, Stefanidis C. Is C-reactive protein reliable for the prediction of renal lesions in infants with urinary tract infection (UTI)? [abstract]. Pediatric Nephrology 1997;11(5):C56. [BIOSIS Previews: PREV199799837360]
Karavanaki 2007 {published data only}
    1. Karavanaki K, Angelos Haliotis F, Sourani M, Kariyiannis C, Hantzi E, Zachariadou L, et al. DMSA scintigraphy in febrile urinary tract infections could be omitted in children with low procalcitonin levels. Infectious Diseases in Clinical Practice 2007;15(6):377-81. [EMBASE: 350135450]
Kassir 2001 {published data only}
    1. Kassir K, Vargas-Shiraishi O, Zaldivar F, Berman M, Singh J, Arrieta A. Cytokine profiles of pediatric patients treated with antibiotics for pyelonephritis: potential therapeutic impact. Clinical & Diagnostic Laboratory Immunology 2001;8(6):1060-3. [MEDLINE: ] - PMC - PubMed
Katz 1993 {published data only}
    1. Katz SP, Barfeld PA, Kaskel FJ. Clinical value of DMSA scan in differentiating acute pyelonephritis (APN) from other urinary tract infections (UTI) in adolescent females [abstract]. Journal of the American Society of Nephrology 1993;4.
Katz 2002 {published data only}
    1. Katz SP, Gromisch DS, Balbi HJ, Vilela MG, Constantatos C, Affan AA. A seven year retrospective review of patients diagnosed with urinary tract infection (UTI) from birth to twenty-four months of age [abstract]. Pediatric Research 2002;51.
Kiker 1982 {published data only}
    1. Kiker JD, Woodside JR, Reed WP, Borden TA, Woodside MD. Urinary lactic dehydrogenase and serum C-reactive protein as means of localizing the site of urinary tract infection in patients with ileal conduits. Journal of Urology 1982;128(4):749-51. [MEDLINE: ] - PubMed
Kilicaslan 2015 {published data only}
    1. Kilicaslan B, Alp H, Yildirim M, Inandi T. Diagnostic value of MAG3 scintigraphy and DMSA scintigraphy in renal parenchyma damage and acute pyelonephritis of children. Cukurova Medical Journal 2016;41(3):464-471. [DOI: 10.17826/cukmedj.237484] - DOI
Kilicaslan 2016 {published data only}
    1. Kilicaslan B, Noyan A, Cengiz N, Sariturk C, Parmaksiz G, Baskin E. Can we differentiate pyelonephritis and cystitis without 99mTc-dimercaptosuccinic acid scan in children? Cukurova Medical Journal 2015;40(3):495-503. [DOI: ]
Kim 2001 {published data only}
    1. Kim S, Kim I, Kim E, Yoo I, Chung Y, Sohn H, et al. Planar and pinhole renal cortical scintigraphic findings correlated to consolidated clinical parameters in acute urinary tract infection [abstract]. Journal of Nuclear Medicine 2001;42.
Koufadaki 2014 {published data only}
    1. Koufadaki AM, Karavanaki KA, Soldatou A, Tsentidis Ch, Sourani MP, Sdogou T, et al. Clinical and laboratory indices of severe renal lesions in children with febrile urinary tract infection. Acta Paediatrica 2014;103(9):e404-9. [MEDLINE: ] - PubMed
Krzemien 2004 {published data only}
    1. Krzemien G, Roszkowska-Blaim M, Kostro I, Szmigielska A, Karpinska M, Sieniawska M, et al. Urinary levels of interleukin-6 and interleukin-8 in children with urinary tract infections to age 2. Medical Science Monitor 2004;10(11):CR593-7. [MEDLINE: ] - PubMed
Krzemien 2016 {published data only}
    1. Krzemien G, Szmigielska A, Turczyn A, Panczyk-Tomaszewska M. Urine interleukin-6, interleukin-8 and transforming growth factor beta1 in infants with urinary tract infection and asymptomatic bacteriuria. Central-European Journal of Immunology 2016;41(3):260-7. [MEDLINE: ] - PMC - PubMed
Krzemien 2017 {published data only}
    1. 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 & Biology 2018;1047:71-80. [MEDLINE: ] - PubMed
Kupperman 2019 {published data only}
    1. Kuppermann N, Dayan PS, Levine DA, Vitale M, Tzimenatos L, Tunik MG, et al. A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA Pediatrics 2019;173(4):342-51. [MEDLINE: ] - PMC - PubMed
Lai 2003 {published data only}
    1. Lai SW, Ng KC. Retrospective analysis of inflammatory parameters in acute pyelonephritis. Scandinavian Journal of Urology & Nephrology 2003;37(3):250-2. [MEDLINE: ] - PubMed
Lee 2006 {published data only}
    1. Lee JH, Son CH, Lee MS, Park YS. Vesicoureteral reflux increases the risk of renal scars: a study of unilateral reflux. Pediatric Nephrology 2006;21(9):1281-4. [MEDLINE: ] - PubMed
Lee 2009 {published data only}
    1. Lee HY, Soh BH, Hong CH, Kim MJ, Han SW. The efficacy of ultrasound and dimercaptosuccinic acid scan in predicting vesicoureteral reflux in children below the age of 2 years with their first febrile urinary tract infection. Pediatric Nephrology 2009;24(10):2009-13. [MEDLINE: ] - PubMed
Lee 2015 {published data only}
    1. Lee IR, Shin JI, Park SJ, Oh JY, Kim JH. Mean platelet volume in young children with urinary tract infection. Scientific Reports 2015;5:10872. [MEDLINE: ] - PMC - PubMed
Lee 2017 {published data only}
    1. Lee JW, Kim SH, Park SJ, Lee KH, Park JH, Kronbichler A, et al. The value of delta neutrophil index in young infants with febrile urinary tract infection. Scientific Reports 2017;7:41265. [MEDLINE: ] - PMC - PubMed
Lee 2017a {published data only}
    1. Lee JW, Park JS, Park KB, Yoo GH, Kim SS, Lee SM. Prediction of renal cortical defect and scar using neutrophil-to-lymphocyte ratio in children with febrile urinary tract infection. Nuklear-Medizin 2017;56(3):109-14. [MEDLINE: ] - PubMed
Lee 2018 {published data only}
    1. Lee JW, Her SM, Kim JH, Lee KH, Eisenhut M, Park SJ, et al. D-dimer as a marker of acute pyelonephritis in infants younger than 24 months with urinary tract infection. Pediatric Nephrology 2018;33(4):631-7. [MEDLINE: ] - PubMed
Lee 2018a {published data only}
    1. Lee JH, Jang SJ, Rhie S. Antinatriuretic phenomena seen in children with acute pyelonephritis may be related to the activation of intrarenal RAAS. Medicine 2018;97(36):e12152. [MEDLINE: ] - PMC - PubMed
Lee 2018b {published data only}
    1. Lee IS, Park YJ, Jin MH, Park JY, Lee HJ, Kim SH, et al. Usefulness of the procalcitonin test in young febrile infants between 1 and 3 months of age. Korean Journal of Pediatrics 2018;61(9):285-90. [EMBASE: 625077903] - PMC - PubMed
Lee 2019 {published data only}
    1. Lee JH. Discrimination of culture negative pyelonephritis in children with suspected febrile urinary tract infection and negative urine culture results. Journal of Microbiology, Immunology & Infection 2019;52(4):598-603. [MEDLINE: ] - PubMed
Leroy 2012 {published data only}
    1. Leroy S, Fernandez-Lopez A, Nikfar R, Romanello C, Bouissou F, Gervaix A, et al. Procalcitonin predicts well acute pyelonephritis and renal scars in children with urinary tract infection [abstract]. Nephrology Dialysis Transplantation 2012;27(Suppl 2):ii547.
Levine 2018 {published data only}
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Lin 2000 {published data only}
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Linne 1994 {published data only}
    1. Linne T, Fituri O, Escobar-Billing R, Karlsson A, Wikstad I, Aperia A, et al. Functional parameters and 99mtechnetium-dimercaptosuccinic acid scan in acute pyelonephritis. Pediatric Nephrology 1994;8(6):694-9. [MEDLINE: ] - PubMed
Lomberg 1992 {published data only}
    1. Lomberg H, Jodal U, Leffler H, De Man P, Svanborg C. Blood group non-secretors have an increased inflammatory response to urinary tract infection. Scandinavian Journal of Infectious Diseases 1992;24(1):77-83. [MEDLINE: ] - PubMed
Lucas‐Saez 2014 {published data only}
    1. Lucas-Saez E, Ferrando-Monleon S, Marin-Serra J, Bou-Monterde R, Fons-Moreno J, Peris-Vidal A, et al. Predictive factors for kidney damage in febrile urinary tract infection. Usefulness of procalcitonin. Nefrologia 2014;34(4):451-7. [MEDLINE: ] - PubMed
Mahyar 2013 {published data only}
    1. Mahyar A, Ayazi P, Maleki MR, Daneshi-Kohan MM, Sarokhani HR, Hashemi HJ, et al. Serum levels of interleukin-6 and interleukin-8 as diagnostic markers of acute pyelonephritis in children. Korean Journal of Pediatrics 2013;56(5):218-23. [MEDLINE: ] - PMC - PubMed
Majd 1991 {published data only}
    1. Majd M, Rushton HG, Jantausch B, Wiedermann BL. Relationship among vesicoureteral reflux, P-fimbriated Escherichia coli, and acute pyelonephritis in children with febrile urinary tract infection. Journal of Pediatrics 1991;119(4):578-85. [MEDLINE: ] - PubMed
Majd 1992 {published data only}
    1. Majd M, Rushton HG. Renal cortical scintigraphy in the diagnosis of acute pyelonephritis. Seminars in Nuclear Medicine 1992;22(2):98-111. [MEDLINE: ] - PubMed
Malaga 1978 {published data only}
    1. Malaga S, Matesanz JL, Dieguez MA, Crespo M. Value of the C reactive protein, urinary lactic dehydrogenase and renal capacity of concentration in the topographic diagnosis of the urinary infection in infancy (author's transl) [Valor de la proteina C reactiva, lactilo-dehidrogenasa urinaria y capacidad renal de concentracion en el diagnostico topografico de la infeccion urinaria en la infancia]. Anales Espanoles de Pediatria 1978;11(6-7):485-96. [MEDLINE: ] - PubMed
Masajtis‐Zagajewska 2015 {published data only}
    1. Masajtis-Zagajewska A, Kurnatowska I, Wajdlich M, Nowicki M. Utility of copeptin and standard inflammatory markers in the diagnostics of upper and lower urinary tract infections. BMC Urology 2015;15:67. [MEDLINE: ] - PMC - PubMed
Mazigh Mrad 2002 {published data only}
    1. Mazigh Mrad S, Fetni I, Rabeh O, Oubich F, Boukthir S, Barsaoui S. Contribution of clinical, biological and radiological parameters in the diagnosis of urinary infection localization [Apport des parametres cliniques biologiques et radiogiques dans le diagnostic de localisation de l'infection urinaire]. Tunisie Medicale 2002;80(10):28-32. [MEDLINE: ] - PubMed
Mohkam 2008 {published data only}
    1. Mohkam M, Karimi A, Karimi H, Sharifian M, Armin S, Dalirani R, et al. Urinary interleukin-8 in acute pyelonephritis of children: a before-after study. Iranian Journal of Kidney Diseases 2008;2(4):193-6. [MEDLINE: ] - PubMed
Moldovan 2015 {published data only}
    1. Moldovan DA, Baghiu MD, Balas A, Truta ST. The value of the "Lab-Score" method in identifying febrile infants at risk for serious bacterial infections. The Journal of Critical Care Medicine 2015;1(1):11-7. [MEDLINE: ] - PMC - PubMed
Montini 2008 {published data only}
    1. Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A, Gobber D, et al. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics 2008;122(5):1064-71. [MEDLINE: ] - PubMed
Montini 2009 {published data only}
    1. Montini G, Zucchetta P, Tomasi L, Talenti E, Rigamonti W, Picco G, et al. Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1. Pediatrics 2009;123(2):e239-46. [MEDLINE: ] - PubMed
Moon 2009 {published data only}
    1. Moon DG, Oh MM, Nam SG, Jin MH, Park HS, Cheon J, et al. Predictive factors for acute scintingraphic lesion and ultimate scar formation in patients with acute febrile UTI [abstract]. Journal of Urology 2009;181(4 Suppl 1):380. [EMBASE: 70113158]
Mussap 2006 {published data only}
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Naseri 2008 {published data only}
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Naseri 2017 {published data only}
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Neuhaus 2008 {published data only}
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References to other published versions of this review

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