Consensus
Le infezioni febbrili delle vie urinarie
FEBRILE URINARY TRACT INFECTIONS
Giovanni Montini1, Anita Ammenti2, Luigi Cataldi3, Roberto Chimenz4, Vassilios Fanos5, Angela La Manna6, Giuseppina Marra7, Marco Materassi8, Paolo Pecile9, Marco Pennesi10, Lorena Pisanello11, Felice Sica12, Antonella Toffolo13
1Clinica Pediatrica, Azienda Ospedaliero-Universitaria “Sant’Orsola-Malpighi”, Bologna;
2Clinica Pediatrica, Azienda Ospedaliero-Universitaria di Parma;
3Dipartimento di Scienze Pediatriche, Policlinico Gemelli, UCSC Roma, Gruppo di Studio di Nefrologia Neonatale della Società Italiana di Neonatologia;
4UO di Nefrologia Pediatrica con dialisi, AOUG Martino, Messina;
5Terapia Intensiva Neonatale, Puericultura e Nido, Azienda Mista Ospedaliero-Universitaria, Cagliari;
6Dipartimento di Pediatria, Seconda Università, Napoli;
7Nefrologia e Dialisi Pediatrica, Policlinico di Milano;
8Nefrologia e Dialisi, Dipartimento di Pediatria, AOU Meyer, Firenze;
9Clinica Pediatrica, Azienda Ospedaliero-Universitaria, Udine;
10Clinica Pediatrica, IRCCS “Burlo Garofolo”, Trieste;
11Pediatra di famiglia, Padova;
12SC di Pediatria Ospedaliera, Azienda Ospedaliero-Universitaria “OORR”, Foggia;
13Ulss 9 Treviso, UO di Pediatria, Oderzo (Treviso)
Giugno 2009 - pagg. 359 -370
Abstract
We present the recommendations, prepared by a working group of the Italian Society of Pediatric
Nephrology, for the diagnosis, treatment, imaging protocol and use of antibiotic
prophylaxis in children having their first febrile urinary tract infection (UTI) between 2 months
and 3 years of age. We also review the evidence from the literature on the long term medical
consequences of post-infectious scars, as the aggressiveness of the diagnostic protocol depends
on the severity of the consequences and the possibility to prevent them. Studies show very heterogeneous
results regarding the population studied, the diagnostic criteria used for the diagnosis
of UTI and the evaluation of outcomes (hypertension, renal damage). It appears that
cohorts were selected on the basis of the presence of high grade reflux or dysplastic kidneys
and a relation between UTI and general morbidities appears ambiguous and not measurable.
Diagnosis of febrile UTIs is based on the clinical suspicion and appropriate urine sample collection
(mid-stream urine or catheterization). An exclusive oral treatment is a reasonable option
to treat a first febrile UTI. Antibiotic prophylaxis is not recommended in children with vesico-
ureteric reflux grade I-II to prevent further UTIs; for severe refluxes (grade III to V), no definite
evidence is available. We propose to perform a renal ultrasound in all children and an
aggressive imaging protocol (micturating cystogram and renal DMSA scan) only in a group
of high risk children selected on the basis of anamnestic, clinical and echographic data.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
1. American Academy of Pediatrics. Practice
parameter: The Diagnosis, Treatment, and
Evaluation of the Initial Urinary Tract Infection
in Febrile Infants and Young Children. Pediatrics
1999;103:843-52.
2. Cincinnati Children Hospital Medical Center (CCHMC). For medical management of presumed first time acute urinary tract infection in children 12 years of age or less. Original publication Date: March, 1999, Revision Publication Date April, 2005.
3. National Institute for Health and Clinical Excellence. Urinary tract infection in children: diagnosis, treatment and long-term management. NICE clinical guideline 54. Issue date: August 2007.
4. Whiting P, Westwood M, Bojke L, et al. Clinical and cost-effectiveness of tests for the diagnosis and evaluation of urinary tract infection (UTI) in children: a systematic review and economic model. Health Technol Assessment 2006;10:36.
5. Buzzetti R, Cannavò RC, Fiammengo P, Marolla L. Nuove opportunità diagnostiche in pediatria: la procalcitonina. Prospettive in Pediatria 2006;36:11-22.
6. Pecile P, Romanello C. Procalcitonin and pyelonephritis in children. Curr Opinion Infect Dis 2007;20:83-7.
7. Carapetis JR, Jaquery Al, Buttery JP, et al. Randomized controlled trial comparing once daily and three times daily. Gentamicin in children with urinary tract infections. Pediatr Infect Dis J 2001;20:240-6.
8. Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV, et al. Extended-interval aminoglycoside administration for children. Pediatrics 2004;14:e111-8.
9. Hoberman A, Hoberman A, Wald ER, et al. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics 1999;104:79-86.
10. Gordon I, Barkovics M, Pindoria S, et al. Primary Vesicoureteric Reflux as a Predictor of Renal Damage in Children Hospitalized with Urinary Tract Infection: A Systematic Review and Meta-Analysis. J Am Soc Nephrol 2003;14:739-44.
11. Riccabona M, Avni FE, Blickman JG, et al. Imaging recommendations in paediatric uroradiology: minutes of the ESPR workgroup session on urinary tract infection, fetal hydronephrosis, urinary tract ultrasonography and voiding cystourethrography. Barcelona, Spain, June 2007. Pediatr Radiol 2008;38:138- 45.
12. Hansson S, Dhamey M, Sigstrom O, et al. Dimercapto-succinic acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection. J Urol 2004; 172:1071-4.
13. Moorthy I, Easty M, McHugh K, et al. The presence of vesicoureteric reflux does not identify a population at risk for renal scarring following a first urinary tract infection. Arch Dis Child 2005;90:733-6.
14. Polito C, Rambaldi PF, Signoriello G, et al. Permanent renal parenchymal defects after febrile UTI are closely associated with vesicoureteric reflux. Pediatr Nephrol 2006;21:521-6.
15. Wennerstrom HS, Hansson S, Jodal U, Sixt R, Stokland E. Renal function 16-to 26 years after the first urinary tract infection in childhood. Arch Pediatr Adolesc Med 2000; 154:339-45.
16. Marra G, Oppezzo C, Ardissino G, et al. Severe vesicoureteral reflux and chronic renal failure: a condition peculiar to male gender? Data from the ItalKid Project. J Pediatr 2004;144:677-81.
17. Hoberman A, Charron M, Hickey R, et al. Imaging studies after a first febrile urinary tract infection in young children. N Engl J Med 2003; 348:195-202.
18. Koff SA. A practical approach to evaluating urinary tract infection in children. Pediatr Nephrol 1991;5:398-400.
19. Kass EJ, Kernen KM, Carey JM. Paediatric urinary tract infection and the necessity of complete urological imaging. BJU Int 2000; 86:94-6.
20. Garin EH, Olavarria F, Garcia Nieto V, et al. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics 2006; 117:626-32.
21. Roussey-Kesler G, Gadjos V, Idres N, et al. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol 2008; 179:674-9.
22. Montini G, Toffolo A, Zucchetta P, et al. Antibiotic treatment for pyelonephritis in children: multicentre randomized controlled noninferiority trial. BMJ 2007;335:386.
23. Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA 2007;298:179-86.
24. Van Eerde AM, Meutgeert MH, De Jong TP, et al. Vescico-ureteral reflux in children with prenatally detected hydronephrosis: a systematic review. Ultrasound Obstet Gynecol 2007;29:463-9.
25. Ismaili K, Hall M, Piepsz A, et al. Primary vesicoureteral reflux detected in neonates with a history of fetal renal pelvis dilatation: a prospective clinical and imaging study. J Pediatr 2006;148:222-7.
26. Huang H, Lai Y, Tsai I. Renal ultrasonography should be done routinely in children with first urinary tract infections. Pediatr Urol 2008;71:439-43.
27. Ataei N, Madani A, Esfahani ST, et al. Screening for vesicoureteral reflux and renal scars in siblings of children with known reflux. Pediatr Nephrol 2004;19:1127-31.
28. Tombesi M. Ferrari CM. Bertolotti JJ. Renal damage in refluxing and non-refluxing siblings of index children with vesicoureteral reflux. Pediatr Nephrol 2005;20:1201-2.
29. Lacroix J, Chabot G, Delage G, et al. Septicemia associated with urinary infection in infants. A propos of 36 cases. Arch Fr Pediatr 1984;41:99-101.
30. Birocchi F, Testa M, Pischedda M. Febbre, batteriemia e sepsi nel lattante. Acta Medica Mediterranea 2005;21:37-43.
31. Gargollo PC, Diamond D. Therapy insight: what nephrologists need to know about primary vesicoureteral reflux. Nat Clin Pract Nephrol 2007;3:551-63.
32. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics 1999;103: 843-52.
33. Goldman M, Lahat E, Strauss S, et al. Imaging after urinary tract infection in male neonates. Pediatrics 2000;105:1232-5.
34. McDonald A, Scranton M, Gillespie R, et al. Voiding cystourethrograms and urinary tract infections: how long to wait? Pediatrics 2000;105:E50.
35. Sathapornwajana P, Dissaneewate P, Mc- Neil E. Timing of voiding cystourethrogram after urinary tract infection. Arch Dis Child 2008;93:229-31.
36. Ascenti G, Chimenz R, Zimbaro G, et al. Potential role of colour-Doppler cystosonography with echocontrast in the screening and follow-up of vesicoureteral reflux. Acta Paediatr 2000;89:1336-9.
37. Ascenti G, Zimbaro G, Mazziotti S, et al. Vesicoureteral reflux: comparison between urosonography and radionuclide cystography. Pediatr Nephrol 2003;18:768-71.
38. Piscitelli A, Galiano R, Serrao F, et al. Which cystography in the diagnosis and grading of vesicoureteral reflux? Pediatr Nephrol 2008; 23:107-10.
39. Bosio M, Manzoni GA. Detection of posterior urethral valves with voiding cystourethrography with echo contrast. J Urol 2002;168: 1711-5.
40. Berrocal T, Gaya F, Arjonilla A. Vesicoureteral reflux: can the urethra be adequately assessed by using contrast-enhanced voiding US of the Bladder? Radiology 2005;234:235-41.
41. Lebowitz RL, Olbing H, Parkkulainen KV, et al. International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 1985;15: 105-9.
42. Jodal U, Smellie JM, Lax H, Hoyer PF. Tenyear results of randomized treatment of children with severe vesicoureteral reflux. Final Report of the International Reflux Study in Children. Pediatr Nephrol 2006;21:785-92.
43. Yeung CK, Godley ML, Dhillon HK, Gordon I, Duffy PG, Ransley PG. The characteristics of primary vesicoureteric reflux in male and female infants with prenatal hydronephrosis. Br J Urol 1997;80:319-27.
44. Assael BM, Guez S, Marra G, et al. Congenital reflux nephropathy: a follow-up of 108 cases diagnosed perinatally. Br J Urol 1998;82: 252-7.
45. Pennesi M, Travan L, Peratoner L, et al. North East Italy Prophylaxis in VUR study group. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics 2008;12: e1489-94.
46. Montini G, Rigon L, Zucchetta P, et al. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics 2008;122:1064-71.
47. Hoberman A, Chao HP, Keller DM, et al. Prevalence of urinary tract infection in febrile infants. J Pediatr 1993;123:17-23.
48. Stephens FD, Hutson JM. Differences in embryogenesis of epispadias, exstrophy-epispadias complex and hypospadias. J Pediatr Urol 2005;1:283-8.
49. Polito C, La Manna A, Rambaldi PF, Nappi B, Mansi L, Di Toro R. High incidence of a generally small kidney and primary vesicoureteral reflux. J Urol 2000;164:479-82.
50. Hohenfellner K, Hunley TE, Brezinska R. ACE I/D gene polymorphism predicts renal damage in congenital uropathies. Pediatr Nephrol 1999;13:514-8.
51. Artifoni L, Negrisolo S, Montini G, et al. Interleukin-8 and CXCR1 receptor functional polymorphisms and susceptibility to acute pyelonephritis. J Urol 2007;177:1102-6.
52. Benfield MR, McDonald R, Sullivan EK, Stablein DM, Tejani A. The 1997 Annual Renal Transplantation in Children Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Transplant 1999;3:152-67.
53. Esbjorner E, Berg U, Hansson S. Epidemiology of chronic renal failure in children: a report from Sweden 1986-1994. Pediatr Nephrol 1997;11:438-42.
54. Sreenarasimhaiah S, Hellerstein S. Urinary tract infections per se do not cause endstage kidney disease. Pediatr Nephrol 1998; 12:210-13.
55. Silva JMP, Santos Diniz JS, Marino VSP, et al. Clinical corse of 735 children and adolescents with primary vesicoureteral reflux. Pediatr Nephrol 2006;21:981-8.
56. McKerrow W, Davidson-Lamb N, Jones PF. Urinary tract infection in children. Br Med J (Clin Res Ed) 1984;289:299-303.
57. Huland H, Busch R. Pyelonephritic scarring in 213 patients with upper and lower urinary tract infections: long-term follow-up. J Urol 1984;132:936-9.
58. Taylor CM. Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years observation. BMJ 1987;295:237-41.
59. Verber IG, Meller ST. Serial 99mTc dimercaptosuccinic acid (DMSA) scans after urinary infections presenting before the age of 5 years. Arch Dis Child 1989;64:1533-7.
60. Beetz R, Schulte-Wissermann H, Troger J, et al. Long-term follow-up of children with surgically treated vesicorenal reflux: postoperative incidence of urinary tract infections, renal scars and arterial hypertension. Eur Urol 1989;16:366-71.
61. Jansen H, Scholtmeijer RJ. Results of surgical treatment of severe vesicoureteric reflux. Retrospective study of reflux grades 4 and 5. Br J Urol 1990;65:413-7.
62. Holland N, Jackson EC, Kazee M, Conrad GR, Yun Rio U. Relation of urinary tract infection and vesicoureteral reflux to scars: followup of thirty-eight patients. J Pediatr 1990;116: s65-71.s
63. Jacobson S, Eklof C, Lins LE, Tidgren B, Winberg J. Development of hypertension and uremia after pyelonephritis in childhood: 27 year follow-up. BMJ 1989;299:703-6.
64. Jakobsson B, Berg U, Svensson L. Renal scarring after acute pyelonephritis. Arch Dis Child 1994;70:111-5.
65. Berg UB. Long term follow-up of renal morphology and function in children with recurrent pyelonephritis. J Urol 1992;148:1715- 20.
66. Arant BS jr. Medical management of mild and moderate vesicoureteral reflux: follow-up studies of infants and young children. A preliminary report of the Southwest Pediatric Nephrology Study Group. J Urol 1992;148: 1683-7.
67. Bailey RR, Lynn KL, McRae CU. Unilateral reflux nephropathy and hypertension. Contrib Nephrol 1984;39:116-25.
68. Goldraich NP, Goldraich IH. Follow-up of conservatively treated children with high and low grade vesicoureteral reflux: a prospective study. J Urol 1992;148:1688-92.
69. Smellie JM, Tamminen-Mobius T, Olbing H, et al. Five-year study of medical or surgical treatment in children with severe reflux: radiological renal findings. The International Reflux Study in Children. Pediatr Nephrol 1992;6:223-30.
70. Weiss R, Duckett J, Spitzer A. Results of a randomized clinical trial of medical versus surgical management of infants and children with grades III and IV primary vesicoureteral reflux (United States). The International Reflux Study in Children. J Urol 1992;148:1667-73.
71. Martinell J, Jodal U, Lidin-Janson G. Pregnancies in women with and without renal scarring after uryinary infections in childhood. BMJ 1990;300:840-4.
72. Martinell J, Jagenburg R, Sivertsson R, Claesson I, Jodal U. Girls prone to urinary infections followed into adulthood. Indices of renal disease. Pediatr Nephrol 1996;10:139-42.
73. Martinell J, Hansson S, Claesson I, Jacobsson B, Lidin-Janson G, Jodal U. Detection of urographic scars in girls with pyelonephritis followed for 13-38 years. Pediatr Nephrol 2000;14:1006-10.
74. Meerrick M, Notghi A, Wilkinsonn G. Long-term follow-up to determine the prognostic value of imaging after urinary tract infections. Part 1: reflux. Arch Dis Child 1995; 72:388-92.
75. Polito C, Marte A, Zamparelli M, Papale MR, Rocco CE, La Manna A. Catch-up growth in children with vesico-ureteric reflux. Pediatr Neprhol 1997;11:164-8.
76. Vernon SJ, Coulthard MG, Lambert HJ, Keir MJ, Matthews JN. New renal scarring in children who at age 3 and 4 years had had normal scans with dimercaptosuccinic acid: follow- up study. BMJ 1997;315:905-8.
77. Smellie JM, Prescod NP, Schaw PJ, Risdon A, Bryant TN. Childhood reflux and urinary infection: a follow-up of 10-41 years in 226 adults. Pediatr Nephrol 1998;12:727-36.
78. Wingen AM, Koskimies O, Olbing H, Seppanen J, Tamminen-Mobius T. Growth and weight gain in children with vesicoureteral reflux receiving medical versus surgical treatment: 10-year results of a prospective, randomized study. International Reflux Study in Children (European Branch). Acta Paediatr 1999;88:56-61.
79. Wennerstrom 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; 18:485-91.
80. Wennerstrom M, Hansson S, Jodal U, Stokland E. Primary and acquired renal scarring in boys and girls with urinary tract infection. J Ped 2000;136:30-4.
81. Nielsen JB, Frokiaer J, Rehling M, Jorgensen TM, Djurhuus JC. A 14-year follow-up of conservative treatment for vesico-ureteric reflux. BJU Int 2000;86:502-7.
82. Smellie JM, Barrat M, Chanyler C. Medical versus surgical treatment in children with severe bilateral vesico-ureteric reflux and bilateral nephropathy: a randomised trial. Lancet 2001;357:1329-33.
83. Mor Y, Leibovitch I, Zalts R, Lotan D, Jonas P, Ramon J. Analysis of long-term outcome of surgically corrected vesico-ureteric reflux. BJU Int 2003;92:97-100.
84. Olbing H, Claesson 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;148:1653-6.
85. Pylkkanen J, Vilska J, Koskimies. The value of level diagnosis of childhood urinary tract infection in predicting renal injury. Acta Paediatr Scand 1981;70:879-83.
86. Winberg J, Claësson I, Jacobsson B, Jodal U, Peterson H. Renal growth after acute pyelonephritis in childhood: An epidemiological approach. In: Hodson CJ, Kincaid-Smith P (Eds). Reflux nephropathy. New York: Masson Publishing USA Inc, 1979:309-22.
87. AAVV. Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years’ observation. Birmingham Reflux Study Group. Br Med J (Clin Res Ed) 1987;295:237-41.
88. McGladdery SL, Aparicio S, Verrier Jones K, Roberts R, Sacks SH. Outcome of pregnancy in an Oxford-Cardiff cohort of women with previous bacteriuria. Q J Med 1992;84: 533-9.
89. Smellie JM. Commentary: management of children with severe vesicoureteral reflux. J Urol 1992;148:1676-8.
90. Lavocat MP, Grandjon D, Guimpied Y. The importance of Tc- DMSA renal schyntigraphy in the follow-up of acute pyelonephritis in children: comparison with urographic data. Nucl Med Commun 1998;19:703-10.
91. Wolfish N, Delbrouck N, Shanon A, et al. Prevalence of hypertension in children with primary vesico-ureteral reflux. J Pediatr 1993; 123:559-63.
92. El Khatib M, Packam DK, Becker GJ, Kincaid Smith P. Pregnancy-related complications in women with reflux nephropaty. Clin Nephrol 1994;3:152-67.
2. Cincinnati Children Hospital Medical Center (CCHMC). For medical management of presumed first time acute urinary tract infection in children 12 years of age or less. Original publication Date: March, 1999, Revision Publication Date April, 2005.
3. National Institute for Health and Clinical Excellence. Urinary tract infection in children: diagnosis, treatment and long-term management. NICE clinical guideline 54. Issue date: August 2007.
4. Whiting P, Westwood M, Bojke L, et al. Clinical and cost-effectiveness of tests for the diagnosis and evaluation of urinary tract infection (UTI) in children: a systematic review and economic model. Health Technol Assessment 2006;10:36.
5. Buzzetti R, Cannavò RC, Fiammengo P, Marolla L. Nuove opportunità diagnostiche in pediatria: la procalcitonina. Prospettive in Pediatria 2006;36:11-22.
6. Pecile P, Romanello C. Procalcitonin and pyelonephritis in children. Curr Opinion Infect Dis 2007;20:83-7.
7. Carapetis JR, Jaquery Al, Buttery JP, et al. Randomized controlled trial comparing once daily and three times daily. Gentamicin in children with urinary tract infections. Pediatr Infect Dis J 2001;20:240-6.
8. Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV, et al. Extended-interval aminoglycoside administration for children. Pediatrics 2004;14:e111-8.
9. Hoberman A, Hoberman A, Wald ER, et al. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics 1999;104:79-86.
10. Gordon I, Barkovics M, Pindoria S, et al. Primary Vesicoureteric Reflux as a Predictor of Renal Damage in Children Hospitalized with Urinary Tract Infection: A Systematic Review and Meta-Analysis. J Am Soc Nephrol 2003;14:739-44.
11. Riccabona M, Avni FE, Blickman JG, et al. Imaging recommendations in paediatric uroradiology: minutes of the ESPR workgroup session on urinary tract infection, fetal hydronephrosis, urinary tract ultrasonography and voiding cystourethrography. Barcelona, Spain, June 2007. Pediatr Radiol 2008;38:138- 45.
12. Hansson S, Dhamey M, Sigstrom O, et al. Dimercapto-succinic acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection. J Urol 2004; 172:1071-4.
13. Moorthy I, Easty M, McHugh K, et al. The presence of vesicoureteric reflux does not identify a population at risk for renal scarring following a first urinary tract infection. Arch Dis Child 2005;90:733-6.
14. Polito C, Rambaldi PF, Signoriello G, et al. Permanent renal parenchymal defects after febrile UTI are closely associated with vesicoureteric reflux. Pediatr Nephrol 2006;21:521-6.
15. Wennerstrom HS, Hansson S, Jodal U, Sixt R, Stokland E. Renal function 16-to 26 years after the first urinary tract infection in childhood. Arch Pediatr Adolesc Med 2000; 154:339-45.
16. Marra G, Oppezzo C, Ardissino G, et al. Severe vesicoureteral reflux and chronic renal failure: a condition peculiar to male gender? Data from the ItalKid Project. J Pediatr 2004;144:677-81.
17. Hoberman A, Charron M, Hickey R, et al. Imaging studies after a first febrile urinary tract infection in young children. N Engl J Med 2003; 348:195-202.
18. Koff SA. A practical approach to evaluating urinary tract infection in children. Pediatr Nephrol 1991;5:398-400.
19. Kass EJ, Kernen KM, Carey JM. Paediatric urinary tract infection and the necessity of complete urological imaging. BJU Int 2000; 86:94-6.
20. Garin EH, Olavarria F, Garcia Nieto V, et al. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. Pediatrics 2006; 117:626-32.
21. Roussey-Kesler G, Gadjos V, Idres N, et al. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. J Urol 2008; 179:674-9.
22. Montini G, Toffolo A, Zucchetta P, et al. Antibiotic treatment for pyelonephritis in children: multicentre randomized controlled noninferiority trial. BMJ 2007;335:386.
23. Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA 2007;298:179-86.
24. Van Eerde AM, Meutgeert MH, De Jong TP, et al. Vescico-ureteral reflux in children with prenatally detected hydronephrosis: a systematic review. Ultrasound Obstet Gynecol 2007;29:463-9.
25. Ismaili K, Hall M, Piepsz A, et al. Primary vesicoureteral reflux detected in neonates with a history of fetal renal pelvis dilatation: a prospective clinical and imaging study. J Pediatr 2006;148:222-7.
26. Huang H, Lai Y, Tsai I. Renal ultrasonography should be done routinely in children with first urinary tract infections. Pediatr Urol 2008;71:439-43.
27. Ataei N, Madani A, Esfahani ST, et al. Screening for vesicoureteral reflux and renal scars in siblings of children with known reflux. Pediatr Nephrol 2004;19:1127-31.
28. Tombesi M. Ferrari CM. Bertolotti JJ. Renal damage in refluxing and non-refluxing siblings of index children with vesicoureteral reflux. Pediatr Nephrol 2005;20:1201-2.
29. Lacroix J, Chabot G, Delage G, et al. Septicemia associated with urinary infection in infants. A propos of 36 cases. Arch Fr Pediatr 1984;41:99-101.
30. Birocchi F, Testa M, Pischedda M. Febbre, batteriemia e sepsi nel lattante. Acta Medica Mediterranea 2005;21:37-43.
31. Gargollo PC, Diamond D. Therapy insight: what nephrologists need to know about primary vesicoureteral reflux. Nat Clin Pract Nephrol 2007;3:551-63.
32. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics 1999;103: 843-52.
33. Goldman M, Lahat E, Strauss S, et al. Imaging after urinary tract infection in male neonates. Pediatrics 2000;105:1232-5.
34. McDonald A, Scranton M, Gillespie R, et al. Voiding cystourethrograms and urinary tract infections: how long to wait? Pediatrics 2000;105:E50.
35. Sathapornwajana P, Dissaneewate P, Mc- Neil E. Timing of voiding cystourethrogram after urinary tract infection. Arch Dis Child 2008;93:229-31.
36. Ascenti G, Chimenz R, Zimbaro G, et al. Potential role of colour-Doppler cystosonography with echocontrast in the screening and follow-up of vesicoureteral reflux. Acta Paediatr 2000;89:1336-9.
37. Ascenti G, Zimbaro G, Mazziotti S, et al. Vesicoureteral reflux: comparison between urosonography and radionuclide cystography. Pediatr Nephrol 2003;18:768-71.
38. Piscitelli A, Galiano R, Serrao F, et al. Which cystography in the diagnosis and grading of vesicoureteral reflux? Pediatr Nephrol 2008; 23:107-10.
39. Bosio M, Manzoni GA. Detection of posterior urethral valves with voiding cystourethrography with echo contrast. J Urol 2002;168: 1711-5.
40. Berrocal T, Gaya F, Arjonilla A. Vesicoureteral reflux: can the urethra be adequately assessed by using contrast-enhanced voiding US of the Bladder? Radiology 2005;234:235-41.
41. Lebowitz RL, Olbing H, Parkkulainen KV, et al. International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 1985;15: 105-9.
42. Jodal U, Smellie JM, Lax H, Hoyer PF. Tenyear results of randomized treatment of children with severe vesicoureteral reflux. Final Report of the International Reflux Study in Children. Pediatr Nephrol 2006;21:785-92.
43. Yeung CK, Godley ML, Dhillon HK, Gordon I, Duffy PG, Ransley PG. The characteristics of primary vesicoureteric reflux in male and female infants with prenatal hydronephrosis. Br J Urol 1997;80:319-27.
44. Assael BM, Guez S, Marra G, et al. Congenital reflux nephropathy: a follow-up of 108 cases diagnosed perinatally. Br J Urol 1998;82: 252-7.
45. Pennesi M, Travan L, Peratoner L, et al. North East Italy Prophylaxis in VUR study group. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics 2008;12: e1489-94.
46. Montini G, Rigon L, Zucchetta P, et al. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics 2008;122:1064-71.
47. Hoberman A, Chao HP, Keller DM, et al. Prevalence of urinary tract infection in febrile infants. J Pediatr 1993;123:17-23.
48. Stephens FD, Hutson JM. Differences in embryogenesis of epispadias, exstrophy-epispadias complex and hypospadias. J Pediatr Urol 2005;1:283-8.
49. Polito C, La Manna A, Rambaldi PF, Nappi B, Mansi L, Di Toro R. High incidence of a generally small kidney and primary vesicoureteral reflux. J Urol 2000;164:479-82.
50. Hohenfellner K, Hunley TE, Brezinska R. ACE I/D gene polymorphism predicts renal damage in congenital uropathies. Pediatr Nephrol 1999;13:514-8.
51. Artifoni L, Negrisolo S, Montini G, et al. Interleukin-8 and CXCR1 receptor functional polymorphisms and susceptibility to acute pyelonephritis. J Urol 2007;177:1102-6.
52. Benfield MR, McDonald R, Sullivan EK, Stablein DM, Tejani A. The 1997 Annual Renal Transplantation in Children Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Transplant 1999;3:152-67.
53. Esbjorner E, Berg U, Hansson S. Epidemiology of chronic renal failure in children: a report from Sweden 1986-1994. Pediatr Nephrol 1997;11:438-42.
54. Sreenarasimhaiah S, Hellerstein S. Urinary tract infections per se do not cause endstage kidney disease. Pediatr Nephrol 1998; 12:210-13.
55. Silva JMP, Santos Diniz JS, Marino VSP, et al. Clinical corse of 735 children and adolescents with primary vesicoureteral reflux. Pediatr Nephrol 2006;21:981-8.
56. McKerrow W, Davidson-Lamb N, Jones PF. Urinary tract infection in children. Br Med J (Clin Res Ed) 1984;289:299-303.
57. Huland H, Busch R. Pyelonephritic scarring in 213 patients with upper and lower urinary tract infections: long-term follow-up. J Urol 1984;132:936-9.
58. Taylor CM. Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years observation. BMJ 1987;295:237-41.
59. Verber IG, Meller ST. Serial 99mTc dimercaptosuccinic acid (DMSA) scans after urinary infections presenting before the age of 5 years. Arch Dis Child 1989;64:1533-7.
60. Beetz R, Schulte-Wissermann H, Troger J, et al. Long-term follow-up of children with surgically treated vesicorenal reflux: postoperative incidence of urinary tract infections, renal scars and arterial hypertension. Eur Urol 1989;16:366-71.
61. Jansen H, Scholtmeijer RJ. Results of surgical treatment of severe vesicoureteric reflux. Retrospective study of reflux grades 4 and 5. Br J Urol 1990;65:413-7.
62. Holland N, Jackson EC, Kazee M, Conrad GR, Yun Rio U. Relation of urinary tract infection and vesicoureteral reflux to scars: followup of thirty-eight patients. J Pediatr 1990;116: s65-71.s
63. Jacobson S, Eklof C, Lins LE, Tidgren B, Winberg J. Development of hypertension and uremia after pyelonephritis in childhood: 27 year follow-up. BMJ 1989;299:703-6.
64. Jakobsson B, Berg U, Svensson L. Renal scarring after acute pyelonephritis. Arch Dis Child 1994;70:111-5.
65. Berg UB. Long term follow-up of renal morphology and function in children with recurrent pyelonephritis. J Urol 1992;148:1715- 20.
66. Arant BS jr. Medical management of mild and moderate vesicoureteral reflux: follow-up studies of infants and young children. A preliminary report of the Southwest Pediatric Nephrology Study Group. J Urol 1992;148: 1683-7.
67. Bailey RR, Lynn KL, McRae CU. Unilateral reflux nephropathy and hypertension. Contrib Nephrol 1984;39:116-25.
68. Goldraich NP, Goldraich IH. Follow-up of conservatively treated children with high and low grade vesicoureteral reflux: a prospective study. J Urol 1992;148:1688-92.
69. Smellie JM, Tamminen-Mobius T, Olbing H, et al. Five-year study of medical or surgical treatment in children with severe reflux: radiological renal findings. The International Reflux Study in Children. Pediatr Nephrol 1992;6:223-30.
70. Weiss R, Duckett J, Spitzer A. Results of a randomized clinical trial of medical versus surgical management of infants and children with grades III and IV primary vesicoureteral reflux (United States). The International Reflux Study in Children. J Urol 1992;148:1667-73.
71. Martinell J, Jodal U, Lidin-Janson G. Pregnancies in women with and without renal scarring after uryinary infections in childhood. BMJ 1990;300:840-4.
72. Martinell J, Jagenburg R, Sivertsson R, Claesson I, Jodal U. Girls prone to urinary infections followed into adulthood. Indices of renal disease. Pediatr Nephrol 1996;10:139-42.
73. Martinell J, Hansson S, Claesson I, Jacobsson B, Lidin-Janson G, Jodal U. Detection of urographic scars in girls with pyelonephritis followed for 13-38 years. Pediatr Nephrol 2000;14:1006-10.
74. Meerrick M, Notghi A, Wilkinsonn G. Long-term follow-up to determine the prognostic value of imaging after urinary tract infections. Part 1: reflux. Arch Dis Child 1995; 72:388-92.
75. Polito C, Marte A, Zamparelli M, Papale MR, Rocco CE, La Manna A. Catch-up growth in children with vesico-ureteric reflux. Pediatr Neprhol 1997;11:164-8.
76. Vernon SJ, Coulthard MG, Lambert HJ, Keir MJ, Matthews JN. New renal scarring in children who at age 3 and 4 years had had normal scans with dimercaptosuccinic acid: follow- up study. BMJ 1997;315:905-8.
77. Smellie JM, Prescod NP, Schaw PJ, Risdon A, Bryant TN. Childhood reflux and urinary infection: a follow-up of 10-41 years in 226 adults. Pediatr Nephrol 1998;12:727-36.
78. Wingen AM, Koskimies O, Olbing H, Seppanen J, Tamminen-Mobius T. Growth and weight gain in children with vesicoureteral reflux receiving medical versus surgical treatment: 10-year results of a prospective, randomized study. International Reflux Study in Children (European Branch). Acta Paediatr 1999;88:56-61.
79. Wennerstrom 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; 18:485-91.
80. Wennerstrom M, Hansson S, Jodal U, Stokland E. Primary and acquired renal scarring in boys and girls with urinary tract infection. J Ped 2000;136:30-4.
81. Nielsen JB, Frokiaer J, Rehling M, Jorgensen TM, Djurhuus JC. A 14-year follow-up of conservative treatment for vesico-ureteric reflux. BJU Int 2000;86:502-7.
82. Smellie JM, Barrat M, Chanyler C. Medical versus surgical treatment in children with severe bilateral vesico-ureteric reflux and bilateral nephropathy: a randomised trial. Lancet 2001;357:1329-33.
83. Mor Y, Leibovitch I, Zalts R, Lotan D, Jonas P, Ramon J. Analysis of long-term outcome of surgically corrected vesico-ureteric reflux. BJU Int 2003;92:97-100.
84. Olbing H, Claesson 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;148:1653-6.
85. Pylkkanen J, Vilska J, Koskimies. The value of level diagnosis of childhood urinary tract infection in predicting renal injury. Acta Paediatr Scand 1981;70:879-83.
86. Winberg J, Claësson I, Jacobsson B, Jodal U, Peterson H. Renal growth after acute pyelonephritis in childhood: An epidemiological approach. In: Hodson CJ, Kincaid-Smith P (Eds). Reflux nephropathy. New York: Masson Publishing USA Inc, 1979:309-22.
87. AAVV. Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years’ observation. Birmingham Reflux Study Group. Br Med J (Clin Res Ed) 1987;295:237-41.
88. McGladdery SL, Aparicio S, Verrier Jones K, Roberts R, Sacks SH. Outcome of pregnancy in an Oxford-Cardiff cohort of women with previous bacteriuria. Q J Med 1992;84: 533-9.
89. Smellie JM. Commentary: management of children with severe vesicoureteral reflux. J Urol 1992;148:1676-8.
90. Lavocat MP, Grandjon D, Guimpied Y. The importance of Tc- DMSA renal schyntigraphy in the follow-up of acute pyelonephritis in children: comparison with urographic data. Nucl Med Commun 1998;19:703-10.
91. Wolfish N, Delbrouck N, Shanon A, et al. Prevalence of hypertension in children with primary vesico-ureteral reflux. J Pediatr 1993; 123:559-63.
92. El Khatib M, Packam DK, Becker GJ, Kincaid Smith P. Pregnancy-related complications in women with reflux nephropaty. Clin Nephrol 1994;3:152-67.
Corrispondenza: giovanni.montini@aosp.bo.it