Identification of Children and Adolescents at Risk for Renal Scarring After a First Urinary Tract Infection: A Meta-analysis With Individual Patient Data | Adolescent Medicine | JAMA Pediatrics | JAMA Network
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1.
Shaikh  N, Ewing  AL, Bhatnagar  S, Hoberman  A.  Risk of renal scarring in children with a first urinary tract infection: a systematic review.  Pediatrics. 2010;126(6):1084-1091.PubMedGoogle ScholarCrossref
2.
Wennerström  M, Hansson  S, Hedner  T, Himmelmann  A, Jodal  U.  Ambulatory blood pressure 16-26 years after the first urinary tract infection in childhood.  J Hypertens. 2000;18(4):485-491.PubMedGoogle ScholarCrossref
3.
Martinell  J, Lidin-Janson  G, Jagenburg  R, Sivertsson  R, Claesson  I, Jodal  U.  Girls prone to urinary infections followed into adulthood: indices of renal disease.  Pediatr Nephrol. 1996;10(2):139-142.PubMedGoogle ScholarCrossref
4.
Jacobson  SH, Eklöf  O, Eriksson  CG, Lins  LE, Tidgren  B, Winberg  J.  Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up.  BMJ. 1989;299(6701):703-706.PubMedGoogle ScholarCrossref
5.
el-Khatib  M, Packham  DK, Becker  GJ, Kincaid-Smith  P.  Pregnancy-related complications in women with reflux nephropathy.  Clin Nephrol. 1994;41(1):50-55.PubMedGoogle Scholar
6.
Patzer  L, Seeman  T, Luck  C, Wühl  E, Janda  J, Misselwitz  J.  Day- and night-time blood pressure elevation in children with higher grades of renal scarring.  J Pediatr. 2003;142(2):117-122.PubMedGoogle ScholarCrossref
7.
Round  J, Fitzgerald  AC, Hulme  C, Lakhanpaul  M, Tullus  K.  Urinary tract infections in children and the risk of ESRF.  Acta Paediatr. 2012;101(3):278-282.PubMedGoogle ScholarCrossref
8.
Gleeson  FV, Gordon  I.  Imaging in urinary tract infection.  Arch Dis Child. 1991;66(11):1282-1283.PubMedGoogle ScholarCrossref
9.
Martinell  J, Claesson  I, Lidin-Janson  G, Jodal  U.  Urinary infection, reflux and renal scarring in females continuously followed for 13-38 years.  Pediatr Nephrol. 1995;9(2):131-136.PubMedGoogle ScholarCrossref
10.
Olbing  H, Claësson  I, Ebel  KD,  et al.  Renal scars and parenchymal thinning in children with vesicoureteral reflux: a 5-year report of the International Reflux Study in Children (European branch).  J Urol. 1992;148(5, pt 2):1653-1656.PubMedGoogle Scholar
11.
Ataei  N, Madani  A, Habibi  R, Khorasani  M.  Evaluation of acute pyelonephritis with DMSA scans in children presenting after the age of 5 years.  Pediatr Nephrol. 2005;20(10):1439-1444.PubMedGoogle ScholarCrossref
12.
Benador  D, Benador  N, Slosman  D, Mermillod  B, Girardin  E.  Are younger children at highest risk of renal sequelae after pyelonephritis?  Lancet. 1997;349(9044):17-19.PubMedGoogle ScholarCrossref
13.
Ditchfield  MR, Summerville  D, Grimwood  K,  et al.  Time course of transient cortical scintigraphic defects associated with acute pyelonephritis.  Pediatr Radiol. 2002;32(12):849-852.PubMedGoogle ScholarCrossref
14.
Goldraich  NP, Goldraich  IH.  Followup of conservatively treated children with high and low grade vesicoureteral reflux: a prospective study.  J Urol. 1992;148(5, pt 2):1688-1692.PubMedGoogle Scholar
15.
Lin  K-Y, Chiu  N-T, Chen  M-J,  et al.  Acute pyelonephritis and sequelae of renal scar in pediatric first febrile urinary tract infection.  Pediatr Nephrol. 2003;18(4):362-365.PubMedGoogle Scholar
16.
Pecile  P, Miorin  E, Romanello  C,  et al.  Procalcitonin: a marker of severity of acute pyelonephritis among children.  Pediatrics. 2004;114(2):e249-e254. http://pediatrics.aappublications.org/content/114/2/e249.long. Accessed April 30, 2013.PubMedGoogle ScholarCrossref
17.
Brandström  P, Nevéus  T, Sixt  R, Stokland  E, Jodal  U, Hansson  S.  The Swedish Reflux Trial in Children, IV: renal damage.  J Urol. 2010;184(1):292-297.PubMedGoogle ScholarCrossref
18.
Coulthard  MG, Lambert  HJ, Keir  MJ.  Do systemic symptoms predict the risk of kidney scarring after urinary tract infection?  Arch Dis Child. 2009;94(4):278-281.PubMedGoogle ScholarCrossref
19.
Preda  I, Jodal  U, Sixt  R, Stokland  E, Hansson  S.  Value of ultrasound in evaluation of infants with first urinary tract infection.  J Urol. 2010;183(5):1984-1988.PubMedGoogle ScholarCrossref
20.
Hoberman  A, Wald  ER, Hickey  RW,  et al.  Oral versus initial intravenous therapy for urinary tract infections in young febrile children.  Pediatrics. 1999;104(1, pt 1):79-86.PubMedGoogle ScholarCrossref
21.
Jakobsson  B, Svensson  L.  Transient pyelonephritic changes on 99mtechnetium–dimercaptosuccinic acid scan for at least five months after infection.  Acta Paediatr. 1997;86(8):803-807.PubMedGoogle ScholarCrossref
22.
Craig  JC, Wheeler  DM, Irwig  L, Howman-Giles  RB.  How accurate is dimercaptosuccinic acid scintigraphy for the diagnosis of acute pyelonephritis? a meta-analysis of experimental studies.  J Nucl Med. 2000;41(6):986-993.PubMedGoogle Scholar
23.
Stewart  GB, Altman  DG, Askie  LM, Duley  L, Simmonds  MC, Stewart  LA.  Statistical analysis of individual participant data meta-analyses: a comparison of methods and recommendations for practice.  PLoS One. 2012;7(10):e46042. doi:10.1371/journal.pone.0046042.PubMedGoogle ScholarCrossref
24.
Hosmer  D, Lemeshow  S.  Applied Logistic Regression. New York, NY: John Wiley & Sons; 2000.
25.
Maldonado  G, Greenland  S.  Simulation study of confounder-selection strategies.  Am J Epidemiol. 1993;138(11):923-936.PubMedGoogle Scholar
26.
Bursac  Z, Gauss  CH, Williams  DK, Hosmer  DW.  Purposeful selection of variables in logistic regression.  Source Code Biol Med. 2008;3:17. doi:10.1186/1751-0473-3-17.PubMedGoogle ScholarCrossref
27.
Gorelick  MH, Shaw  KN.  Clinical decision rule to identify febrile young girls at risk for urinary tract infection.  Arch Pediatr Adolesc Med. 2000;154(4):386-390.PubMedGoogle ScholarCrossref
28.
Shaikh  N, Morone  NE, Lopez  J,  et al.  Does this child have a urinary tract infection?  JAMA. 2007;298(24):2895-2904.PubMedGoogle ScholarCrossref
29.
Shaikh  N, Hoberman  A, Rockette  HE, Kurs-Lasky  M.  Identifying children with vesicoureteral reflux: a comparison of 2 approaches.  J Urol. 2012;188(5):1895-1899.PubMedGoogle ScholarCrossref
30.
Royston  P, Moons  KG, Altman  DG, Vergouwe  Y.  Prognosis and prognostic research: developing a prognostic model.  BMJ. 2009;338:b604. doi:10.1136/bmj.b604.PubMedGoogle ScholarCrossref
31.
Agras  K, Ortapamuk  H, Naldöken  S, Tuncel  A, Atan  A.  Resolution of cortical lesions on serial renal scans in children with acute pyelonephritis.  Pediatr Radiol. 2007;37(2):153-158.PubMedGoogle ScholarCrossref
32.
Biggi  A, Dardanelli  L, Cussino  P,  et al.  Prognostic value of the acute DMSA scan in children with first urinary tract infection.  Pediatr Nephrol. 2001;16(10):800-804.PubMedGoogle ScholarCrossref
33.
Bressan  S, Andreola  B, Zucchetta  P,  et al.  Procalcitonin as a predictor of renal scarring in infants and young children.  Pediatr Nephrol. 2009;24(6):1199-1204.PubMedGoogle ScholarCrossref
34.
Camacho  V, Estorch  M, Fraga  G,  et al.  DMSA study performed during febrile urinary tract infection: a predictor of patient outcome?  Eur J Nucl Med Mol Imaging. 2004;31(6):862-866.PubMedGoogle ScholarCrossref
35.
Craig  JC, Irwig  LM, Knight  JF, Sureshkumar  P, Roy  LP.  Symptomatic urinary tract infection in preschool Australian children.  J Paediatr Child Health. 1998;34(2):154-159.PubMedGoogle ScholarCrossref
36.
Imperiale  A, Olianti  C, Sestini  S,  et al.  123I-hippuran renal scintigraphy with evaluation of single-kidney clearance for predicting renal scarring after acute urinary tract infection: comparison with 99mTc-DMSA scanning.  J Nucl Med. 2003;44(11):1755-1760.PubMedGoogle Scholar
37.
Karavanaki  K, Angelos Haliotis  F, Sourani  M,  et al.  DMSA scintigraphy in febrile urinary tract infections could be omitted in children with low procalcitonin levels.  Infect Dis Clin Pract. 2007;15(6):377-381.Google ScholarCrossref
38.
Kotoula  A, Gardikis  S, Tsalkidis  A,  et al.  Comparative efficacies of procalcitonin and conventional inflammatory markers for prediction of renal parenchymal inflammation in pediatric first urinary tract infection.  Urology. 2009;73(4):782-786.PubMedGoogle ScholarCrossref
39.
Levtchenko  E, Lahy  C, Levy  J, Ham  H, Piepsz  A.  Treatment of children with acute pyelonephritis: a prospective randomized study.  Pediatr Nephrol. 2001;16(11):878-884.PubMedGoogle ScholarCrossref
40.
Montini  G, Toffolo  A, Zucchetta  P,  et al.  Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial.  BMJ. 2007;335(7616):386-388.PubMedGoogle ScholarCrossref
41.
Oh  MM, Jin  MH, Bae  JH, Park  HS, Lee  JG, Moon  G.  The role of vesicoureteral reflux in acute renal cortical scintigraphic lesion and ultimate scar formation.  J Urol. 2008;180(5):2167-2170.PubMedGoogle ScholarCrossref
42.
Prat  C, Domínguez  J, Rodrigo  C,  et al.  Elevated serum procalcitonin values correlate with renal scarring in children with urinary tract infection.  Pediatr Infect Dis J. 2003;22(5):438-442.PubMedGoogle Scholar
43.
Preda  I, Jodal  U, Sixt  R, Stokland  E, Hansson  S.  Imaging strategy for infants with urinary tract infection: a new algorithm.  J Urol. 2011;185(3):1046-1052.PubMedGoogle ScholarCrossref
44.
Rosenberg  AR, Rossleigh  MA, Brydon  MP, Bass  SJ, Leighton  DM, Farnsworth  RH.  Evaluation of acute urinary tract infection in children by dimercaptosuccinic acid scintigraphy: a prospective study.  J Urol. 1992;148(5, pt 2):1746-1749.PubMedGoogle Scholar
45.
Sheu  JN, Chang  HM, Chen  SM, Hung  TW, Lue  KH.  The role of procalcitonin for acute pyelonephritis and subsequent renal scarring in infants and young children.  J Urol. 2011;186(5):2002-2008.PubMedGoogle ScholarCrossref
46.
Spasojević-Dimitrijeva  B, Zivković  M, Stanković  A, Stojković  L, Kostić  M.  The IL-6 −174G/C polymorphism and renal scarring in children with first acute pyelonephritis.  Pediatr Nephrol. 2010;25(10):2099-2106.PubMedGoogle ScholarCrossref
47.
Stokland  E, Hellström  M, Jacobsson  B, Jodal  U, Sixt  R.  Renal damage one year after first urinary tract infection: role of dimercaptosuccinic acid scintigraphy.  J Pediatr. 1996;129(6):815-820.PubMedGoogle ScholarCrossref
48.
Taskinen  S, Rönnholm  K.  Post-pyelonephritic renal scars are not associated with vesicoureteral reflux in children.  J Urol. 2005;173(4):1345-1348.PubMedGoogle ScholarCrossref
49.
Tuerlinckx  D, Vander Borght  T, Glupczynski  Y,  et al.  Is procalcitonin a good marker of renal lesion in febrile urinary tract infection?  Eur J Pediatr. 2005;164(10):651-652.PubMedGoogle ScholarCrossref
50.
Tullus  K, Fituri  O, Linné  T,  et al.  Urine interleukin-6 and interleukin-8 in children with acute pyelonephritis, in relation to DMSA scintigraphy in the acute phase and at 1-year follow-up.  Pediatr Radiol. 1994;24(7):513-515.PubMedGoogle ScholarCrossref
51.
Zaffanello  M, Cataldi  L, Brugnara  M, Franchini  M, Bruno  C, Fanos  V.  Hidden high-grade vesicoureteral reflux is the main risk factor for chronic renal damage in children under the age of two years with first urinary tract infection.  Scand J Urol Nephrol. 2009;43(6):494-500.PubMedGoogle ScholarCrossref
52.
Zaki  M, Badawi  M, Al Mutari  G, Ramadan  D, Adul Rahman  M.  Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study using 99mTc DMSA renal scintigraphy.  Pediatr Nephrol. 2005;20(8):1116-1119.PubMedGoogle ScholarCrossref
53.
Ammenti  A, Cataldi  L, Chimenz  R,  et al; Italian Society of Pediatric Nephrology.  Febrile urinary tract infections in young children: recommendations for the diagnosis, treatment and follow-up.  Acta Paediatr. 2012;101(5):451-457.PubMedGoogle ScholarCrossref
54.
Roberts  KB; Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management.  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. 2011;128(3):595-610.PubMedGoogle ScholarCrossref
55.
National Collaborating Centre for Women’s and Children’s Health.  Urinary tract infection in children: diagnosis, treatment and long term management.http://www.nice.org.uk/nicemedia/live/11819/36028/36028.pdf. Accessed April 30, 2013.
56.
Royal Children's Hospital Melbourne.  Urinary tract infection guideline.http://www.rch.org.au/clinicalguide/guideline_index/Urinary_Tract_Infection_Guideline/. Accessed April 30, 2013.
57.
Honkinen  O, Jahnukainen  T, Mertsola  J, Eskola  J, Ruuskanen  O.  Bacteremic urinary tract infection in children.  Pediatr Infect Dis J. 2000;19(7):630-634.PubMedGoogle ScholarCrossref
58.
Jantunen  ME, Siitonen  A, Ala-Houhala  M,  et al.  Predictive factors associated with significant urinary tract abnormalities in infants with pyelonephritis.  Pediatr Infect Dis J. 2001;20(6):597-601.PubMedGoogle ScholarCrossref
59.
Berg  UB, Johansson  SB.  Age as a main determinant of renal functional damage in urinary tract infection.  Arch Dis Child. 1983;58(12):963-969.PubMedGoogle ScholarCrossref
60.
Pylkkänen  J, Vilska  J, Koskimies  O.  The value of level diagnosis of childhood urinary tract infection in predicting renal injury.  Acta Paediatr Scand. 1981;70(6):879-883.PubMedGoogle ScholarCrossref
61.
Doganis  D, Siafas  K, Mavrikou  M,  et al.  Does early treatment of urinary tract infection prevent renal damage?  Pediatrics. 2007;120(4):e922-e928. doi:10.1542/peds.2006-2417.PubMedGoogle ScholarCrossref
62.
Hewitt  IK, Zucchetta  P, Rigon  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):486-490.PubMedGoogle ScholarCrossref
63.
Huang  YY, Chen  MJ, Chiu  NT, Chou  HH, Lin  KY, Chiou  YY.  Adjunctive oral methylprednisolone in pediatric acute pyelonephritis alleviates renal scarring.  Pediatrics. 2011;128(3):e496-e504. doi:10.1542/peds.2010-0297.PubMedGoogle Scholar
64.
Shaikh  N.  Corticosteroids for Children With Febrile Urinary Tract Infections (STARRS).http://clinicaltrials.gov/ct2/show/NCT01391793. Accessed March 19, 2014.
65.
Keren  R, Carpenter  MA, Hoberman  A,  et al.  Rationale and design issues of the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study.  Pediatrics. 2008;122(suppl 5):S240-S250.PubMedGoogle ScholarCrossref
Original Investigation
October 2014

Identification of Children and Adolescents at Risk for Renal Scarring After a First Urinary Tract Infection: A Meta-analysis With Individual Patient Data

Author Affiliations
  • 1Division of General Academic Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 2Division of General Academic Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
  • 3Department of Paediatric Nephrology, Children’s Hospital at Westmead and Sydney School of Public Health, University of Sydney, Sydney, Australia
  • 4Departments of Operating Rooms and Health Evidence, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands
  • 5Department of Woman’s and Child’s Health, University of Padova, Padova, Italy
  • 6Department of Pediatric Surgery, Alexandroupolis University Hospital, Democritus University of Thrace School of Medicine, Alexandroupolis, Greece
  • 7Dialysis Unit, Department of Pediatrics and Nephrology, Azienda Ospedaliero Universitaria Sant’Orsola-Malpighi Bologna, Bologna, Italy
  • 8Department of Pediatrics, Germans Trias i Pujol University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
  • 9Department of Pediatric Surgery, Children’s Hospital, University of Helsinki, Helsinki, Finland
  • 10Service de Pédiatrie, Université Catholique de Louvain, University Medical Centre Mont-Godinne, Yvoir, Belgium
JAMA Pediatr. 2014;168(10):893-900. doi:10.1001/jamapediatrics.2014.637
Abstract

Importance  No studies have systematically examined the accuracy of clinical, laboratory, and imaging variables in detecting renal scarring in children and adolescents with a first urinary tract infection.

Objectives  To identify independent prognostic factors for the development of renal scarring and to combine these factors in prediction models that could be useful in clinical practice.

Data Sources  MEDLINE and EMBASE.

Study Selection  We included patients aged 0 to 18 years with a first urinary tract infection who underwent follow-up renal scanning with technetium Tc 99m succimer at least 5 months later.

Data Extraction and Synthesis  We pooled individual patient data from 9 cohort studies.

Main Outcomes and Measures  We examined the association between predictor variables assessed at the time of the first urinary tract infection and the development of renal scarring. Renal scarring was defined by the presence of photopenia on the renal scan. We assessed the following 3 models: clinical (demographic information, fever, and etiologic organism) and ultrasonographic findings (model 1); model 1 plus serum levels of inflammatory markers (model 2); and model 2 plus voiding cystourethrogram findings (model 3).

Results  Of the 1280 included participants, 199 (15.5%) had renal scarring. A temperature of at least 39°C, an etiologic organism other than Escherichia coli, an abnormal ultrasonographic finding, polymorphonuclear cell count of greater than 60%, C-reactive protein level of greater than 40 mg/L, and presence of vesicoureteral reflux were all associated with the development of renal scars (P ≤ .01 for all). Although the presence of grade IV or V vesicoureteral reflux was the strongest predictor of renal scarring, this degree of reflux was present in only 4.1% of patients. The overall predictive ability of model 1 with 3 variables (temperature, ultrasonographic findings, and etiologic organism) was only 3% to 5% less than the predictive ability of models requiring a blood draw and/or a voiding cystourethrogram. Patients with a model 1 score of 2 or more (21.7% of the sample) represent a particularly high-risk group in whom the risk for renal scarring was 30.7%. At this cutoff, model 1 identified 44.9% of patients with eventual renal scarring.

Conclusions and Relevance  Children and adolescents with an abnormal renal ultrasonographic finding or with a combination of high fever (≥39°C) and an etiologic organism other than E coli are at high risk for the development of renal scarring.

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