ARTICLE

Early Treatment of Acute Pyelonephritis in Children

Fails to Reduce Renal Scarring: Data From the Italian
Renal Infection Study Trials
Ian K. Hewitt, MBBS, FRACPa, Pietro Zucchetta, MDb, Luca Rigon, MDc, Francesca Maschio, MDd, Pier Paolo Molinari, MDe, Lisanna Tomasi, MDf,
Antonella Toffolo, MDg, Luigi Pavanello, MDh, Carlo Crivellaro, MDi, Stefano Bellato, MDj, Giovanni Montini, MDf

aDepartment of Pediatric Nephrology, Princess Margaret Hospital, Perth, Australia; Departments of bNuclear Medicine and fPediatric Nephrology, Azienda Ospedaliera-
University of Padua, Padua, Italy; cPediatric Unit, Camposampiero Hospital, Padua, Italy; dPediatric Unit, Mestre Hospital, Mestre, Italy; ePediatric Unit, Bologna General
Hospital, Bologna, Italy; gPediatric Unit, Motta di Livenza Hospital, Livenza, Italy; hPediatric Unit, Castelfranco Hospital, Castelfranco, Italy; iPediatric Unit, Chioggia Hospital,
Chioggia, Italy; jPediatric Unit, Arzignano Hospital, Arzignano, Italy

The authors have indicated they have no financial relationships relevant to this article to disclose.

What’s Known on This Subject What This Study Adds

Renal scarring is a frequent outcome of acute pyelonephritis in children. The American Early treatment of acute pyelonephritis in infants and young children had no significant
Academy of Pediatrics expressed concern regarding any delay in the treatment of febrile effect on the incidence of subsequent renal scarring. Furthermore, no difference in
UTIs, supporting the concept that such delay increases the subsequent risk of kidney scarring rates was observed when infants and young children were compared with older
damage. children.

ABSTRACT
OBJECTIVES. The American Academy of Pediatrics recommendation for febrile infants
and young children suspected of having a urinary tract infection is early antibiotic
treatment, given parenterally if necessary. In support of this recommendation, data www.pediatrics.org/cgi/doi/10.1542/
peds.2007-2894
suggesting that delay in treatment of acute pyelonephritis increases the risk of kidney
damage are cited. Because the risk was not well defined, we investigated renal doi:10.1542/peds.2007-2894
scarring associated with delayed versus early treatment of acute pyelonephritis in Both study protocols, IRIS 1 NCT00161330
and IRIS 2 NCT00156546, have been
children. registered at www.clinicaltrials.gov.
METHODS. The research findings are derived from 2 multicenter, prospective, random- Key Words
ized, controlled studies, Italian Renal Infection Study 1 and 2, whose primary urinary tract infection, renal scar,
technetium-99m-dimercaptosuccinic acid
outcomes dealt with initial antibiotic treatment and subsequent prophylaxis, respec- scan, antibiotic treatment
tively. From the 2 studies, we selected the 287 children with confirmed pyelone- Abbreviations
phritis on acute technetium-99m-dimercaptosuccinic acid scans who underwent IRIS—Italian Renal Infection Study
repeat scanning to detect scarring 12 months later. The children were 1 month to ⬍7 DMSA—technetium-99m-
dimercaptosuccinic acid
years of age when they presented with their first recognized episode of acute UTI— urinary tract infection
pyelonephritis in northeast Italy.
Accepted for publication Dec 4, 2007
RESULTS. Progressive delay in antibiotic treatment of acute pyelonephritis from ⬍1 to Address correspondence to Giovanni Montini,
ⱖ5 days after the onset of fever was not associated with any significant increase in MD, Nephrology, Dialysis, and Transplant Unit,
Pediatric Department, Azienda Ospedaliera di
the risk of scarring on technetium-99m-dimercaptosuccinic acid scans obtained 1 Padova, Via Giustiniani, 3, 35128 Padova, Italy.
year later. The risk of scarring remained relatively constant at 30.7 ⫾ 7%. Clinical E-mail: montini@pediatria.unipd.it
and laboratory indices of inflammation were comparable in all groups, as was the PEDIATRICS (ISSN Numbers: Print, 0031-4005;
Online, 1098-4275). Copyright © 2008 by the
incidence of vesicoureteric reflux. American Academy of Pediatrics

CONCLUSIONS. Early treatment of acute pyelonephritis in infants and young children had
no significant effect on the incidence of subsequent renal scarring. Furthermore, there was no significant difference
in the rate of scarring after acute pyelonephritis when infants and young children were compared with older
children. Pediatrics 2008;122:486–490

R ENAL SCARRING IS a frequent outcome of acute pyelonephritis in children,1–3 with urinary tract infection (UTI)
now being considered the most common, serious, bacterial infection that occurs in infancy and early childhood
in the developed world.4 The adverse long-term effects of UTI, such as hypertension, proteinuria, and the possibility
of chronic renal failure, are secondary to the presence of scarring.5 The American Academy of Pediatrics identified the
population at greatest risk of incurring renal damage from UTI as being infants and young children with UTI and
fever.6 In its primary recommendation, it expressed concern regarding any delay in the diagnosis and treatment of
febrile UTI, citing clinical and experimental data supporting the concept that a delay in the treatment of acute
pyelonephritis increases the risk of kidney damage.7,8 Both cited studies included small numbers of children, were

486 HEWITT et al
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retrospective, and had severe limitations. In the first
study,7 no statistical analysis was performed to support
the authors’ assertions. The second article8 provided no
information on patient selection, and the diagnosis of
pyelonephritis was poorly defined. This is the first study
to examine in a detailed manner the issue of delayed
treatment of acute pyelonephritis as a risk factor for
latter scarring, with a large cohort of children presenting
with their first recognized episode of acute pyelonephri-
tis.
METHODS
Study Group
As part of 2 controlled, randomized, multicenter, open-
label, parallel-group trials with children presenting with
their first documented episode of acute pyelonephritis in
northeast Italy, that is, Italian Renal Infection Study
(IRIS) 1 and 2, we identified 287 children. IRIS 1 dealt
with antibiotic treatment of the initial infection, and
children were assigned randomly to receive orally ad-
ministered co-amoxiclav (50 mg/kg per day, in 3 divided
doses, for 10 days) or parenterally administered ceftri-
axone (50 mg/kg per day, in a single dose, for 3 days)
followed by orally administered co-amoxiclav (50 mg/kg
per day, in 3 divided doses, for 7 days).9 This study took
place between June 2000 and July 2005. IRIS 2 was a
trial of antibiotic prophylaxis versus no treatment in the
follow-up period that was completed in August 2006.10
All patients were reevaluated according to protocol at 72
hours after commencement of antibiotic treatment, with
urine microscopy and culture, full blood counts, and
measurements of indices of inflammation. Both study
protocols were approved by the ethics committees of
each of the 28 participating centers. Written informed
consent was obtained from the parents of all partici-
pants.
Children recruited to IRIS 1 and 2 were 1 month to
⬍7 years of age at the time of their first recognized
episode of acute pyelonephritis. The diagnosis was based
on a confirmed UTI, with a white blood cell count of ⱖ25
cells per ␮L (1⫹ with a dipstick) and growth of a single
microorganism at ⱖ100 000 colony-forming units per
mL in 2 consecutive tests, as well as ⱖ2 of the following
criteria: fever of ⱖ38°C (in the first 6 months of life,
fever was not an essential criterion), inflammation
indices in the first 48 hours (erythrocyte sedimenta-
tion rate of ⱖ30 mm/hour and/or C-reactive protein
level ⱖ3 times the upper limit of the reference range),
or neutrophil levels above normal values for age.11
Although all children recruited to IRIS 1 and 2 were
considered for inclusion, this analysis was restricted to
children from the 2 studies with acute, positive, tech-
netium-99m-dimercaptosuccinic acid (DMSA) scans
performed within 10 days after the commencement of
antibiotic treatment, with follow-up scans completed 12
months later. DMSA scanning is considered the standard
method for the diagnosis of acute pyelonephritis and
renal scars.12 In addition, normal prenatal ultrasound
results were required for all children. Exclusion criteria
included creatinine clearance of ⱕ70 mL/minute per
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1.73 m2 (with the formula described by Schwartz et al13),
documented renal and/or urologic abnormalities, and
any previous antibiotic administration for that episode of
infection.
Procedures and Scintigraphy
A detailed history was obtained from the parents accord-
ing to protocol, and the duration of fever before admis-
sion was documented. After urine specimens were ob-
tained, the children were treated with antibiotics. Acute
DMSA scans were obtained to confirm acute pyelone-
phritis, with scanning 12 months later to assess the
presence or absence of scarring at the site of previously
documented infection.
Static renal scintigraphy was performed as described
previously.14 Focal or diffuse areas of decreased uptake
in the first scan, without evidence of cortical loss, were
considered indicative of acute pyelonephritis. Renal
scarring on the second scan was defined as decreased
uptake with distortion of the contours or cortical thin-
ning with loss of parenchymal volume in the region of
the previous acute pyelonephritis. Two nuclear medicine
physicians who were blinded to the patients’ test results
interpreted the scans independently. Discrepancies,
which occurred in 10.5% of cases, were resolved
through discussion between the evaluators.
Statistical Analyses
All statistical calculations were performed with Stata 8.1
(Stata, Chicago, IL). Results are reported as means ⫾ SD
for continuous variables and as proportions for categor-
ical variables. Differences between groups for continu-
ous variables were analyzed with Student’s t test and
1-way analysis of variance; categorical variables were
analyzed with Pearson’s ␹2 test or Fisher’s exact test.
Because the data were derived from 2 multicenter, pro-
spective, controlled studies, statistical analyses pro-
ceeded as follows. Univariate analyses were performed
for all single variables considered in the study. The data
were then stratified according to duration of fever (in
days) before treatment, to assess the homogeneity of the
stratification. Bivariate analyses were performed to as-
sess the relationships of the independent variables
(among which the principal variable was the duration of
fever), with the dependent variable being evidence of
scarring on the 12-month DMSA scan. Correlation co-
efficients were calculated for all measured variables, for
evidence of colinearity. Finally, logistic regression mod-
els were used to calculate odds ratios, with particular
interest in the variables that were affected by the dura-
tion of fever before antibiotic treatment. All P values
were 2-sided.
RESULTS
A total of 298 children were identified according to our
selection criteria. Subsequent exclusions included 5 pa-
tients for whom there was uncertainty regarding the
exact duration of fever before commencement of ther-
apy and 6 patients who were deemed to have a new scar
not at the site of the original pyelonephritis. This left 287
PEDIATRICS Volume 122, Number 3, September 2008 487
 TABLE 1 Risk of Scarring Related to Duration of Fever Before
Antibiotic Treatment Among Patients 1 Month to <7
Years of Age at the Time of Acute Pyelonephritis
Duration of Timing of Initial DMSA Scan DMSA Scan Duration of Fever
Fever Before DMSA Scan in at 12 mo, n With Scar, n After Antibiotic
Antibiotic Relation to (%) Treatment, Mean
Treatment, d Antibody ⫾ SD, d
Therapy, Mean
⫾ SD, d
⬍1 5.3 ⫾ 2.5 43 15 (35) 1.8 ⫾ 0.9
1 5.2 ⫾ 2.3 88 24 (27) 1.7 ⫾ 1.1
2 4.6 ⫾ 2.2 61 24 (39) 1.5 ⫾ 0.9
3 4.2 ⫾ 1.9 30 7 (23) 1.7 ⫾ 0.9
4 4.2 ⫾ 2.5 26 7 (27) 1.4 ⫾ 0.5
ⱖ5 4.3 ⫾ 2.3 39 12 (31) 1.5 ⫾ 1.6
Total 4.7 ⫾ 2.6 287 89 (31) 1.6 ⫾ 0.9
children (198 girls and 89 boys; mean age: 15 months)
who fulfilled all criteria and were included in the anal-
ysis. Treatment of the acute infection was as follows: oral
co-amoxiclav therapy for 10 days for 149 children and
initial parenteral ceftriaxone treatment for 3 days, fol-
lowed by oral co-amoxiclav therapy for 7 days, for 138
children. Escherichia coli was the pathogen responsible in
⬎90% of the urine cultures. Urine sterilization rates
were comparable between the 2 treatment groups
(99%), as were antibiotic resistance rates.
When all children were assessed for the presence of
scarring on DMSA scans at the site of pyelonephritis
documented in the acute study, there was no significant
difference in the incidence of scarring with progressive
delay in the initiation of antibiotic therapy from ⬍1 to
ⱖ5 days after the onset of fever (rate of scarring: 30.7 ⫾
7.0%; odds ratio: 0.99; 95% confidence interval: 0.65–
1.51; P ⫽ .97) (Table 1). When analysis was restricted to
the 227 children who were 1 month to 2 years of age at
the time of pyelonephritis, similar results were obtained
(rate of scarring: 30.4 ⫾ 4.9%; odds ratio: 1.35; 95%
confidence interval: 0.62–2.94; P ⫽ .45). Finally, we
divided the children into 4 age quartiles for the first 2
years and a fifth group between 2 and ⬍7 years of age,
with no pattern of increased scarring appearing in a
statistical analysis in relation to age (P ⫽ .19) (Table 2).
When results were evaluated for severity of illness by
using indices of inflammation, levels of fever at admis-
sion were similar for all groups, as were total white blood
cell counts (Table 3). There was a modest reduction in
the neutrophil count for patients who had a fever for ⱖ4
days before therapy, which did not reach significance
(P ⫽ .08). The C-reactive protein level was consistently
elevated and showed no significant difference with a
delay in treatment, whereas the erythrocyte sedimenta-
tion rate demonstrated a significant increase with in-
creasing duration of illness (P ⫽ .02). The failure of early
antibiotic treatment to reduce subsequent scarring sig-
nificantly was seen despite the effectiveness of antibiot-
ics in causing resolution of fever a mean of 1.6 ⫾ 0.1
days after administration (Table 1).
488 HEWITT et al
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TABLE 2 Risk of Scarring Related to Age Among Patients 1 Month
to <7 Years of Age at the Time of Acute Pyelonephritis
Age No. of Patients Scarring, n (%)
1–6 mo 110 39 (35)
7–12 mo 74 16 (22)
13–18 mo 32 10 (31)
19–24 mo 23 6 (26)
24 mo to ⬍7 y 48 18 (38)
Total 287 89 (31)
DISCUSSION
There is an almost universally held view in the literature
and publicized evidence-based clinical guidelines that
early aggressive therapy of acute pyelonephritis in chil-
dren, particularly very young children, is essential to
reduce the subsequent frequency and degree of scar-
ring.15–20 The most recent clinical practice guidelines of
the American Academy of Pediatrics6 recommend the
early administration of antibiotics, either orally or intra-
venously, for infants and young children with suspected
or proven UTIs or pyelonephritis. As evidence in support
of this, 2 articles are cited, in which “clinical and exper-
imental data support the concept that delay in instituting
appropriate treatment of acute pyelonephritis increases
the risk of kidney damage.”
Both articles report retrospective chart reviews with
limited patient numbers. The first7 identified 37 children
over a 15-year period who were deemed to have ac-
quired scars after either pyelonephritis or pyrexia of
unknown origin. Insufficient detail was provided and no
statistical analysis was performed to support the authors’
assertion that “episodes of acute pyelonephritis should
be treated early and aggressively to prevent renal scar-
ring.”7 The second article8 described 52 children, 1 to 12
years of age (with no information on patient selection),
for whom attempts were made in discussions of the
symptoms with parents to determine when UTIs first
commenced, with the diagnosis of acute pyelonephritis
being poorly defined. More recently, Hoberman et al,21
in a large prospective study of oral versus intravenous
therapy for UTIs in young febrile children, reported a
slightly higher but not significantly different incidence of
scarring among children who presented for care after
ⱖ24 hours of fever, compared with those who presented
sooner. Those authors noted that their findings were
“consistent with the prevailing opinion that scarring is
more common when there is either a delay in initiating
treatment or when there is a sluggish response to ther-
apy.”21 Additional reasons for the ready acceptance of
the idea that early antibiotic treatment reduces subse-
quent scarring, in the absence of good scientific evi-
dence, stem from several sources, including the effec-
tiveness of antibiotics in promoting rapid clinical
recovery, laboratory data that demonstrate early reduc-
tions in inflammatory cytokine levels,22,23 and limited
animal studies indicating that antibiotic treatment ⬍24
hours after direct infection of the kidney can prevent
significant inflammation and subsequent scarring.24,25
Our study, involving large numbers of patients, is the
 TABLE 3 Indices of Inflammation for All Patients
Duration of Fever, Fever at Presentation, White Blood Cell Count, Neutrophil Count, ESR, Mean ⫾ SD, CRP Level, Mean ⫾ SD
d (N ⫽ 287) Mean ⫾ SD, °C (N ⫽ 287) Mean ⫾ SD, Cells per Mean ⫾ SD, Cells mm/h (N ⫽ 134) (N ⫽ 277)a
mL (N ⫽ 282) per mL (N ⫽ 231)
⬍1 38.8 ⫾ 0.7 18 171 ⫾ 6639 11 067 ⫾ 4526 54 ⫾ 23 22 ⫾ 22
1 38.9 ⫾ 0.9 18 452 ⫾ 6890 11 953 ⫾ 6073 60 ⫾ 28 20 ⫾ 30
2 38.7 ⫾ 0.9 19 778 ⫾ 7116 12 298 ⫾ 5002 69 ⫾ 27 25 ⫾ 17
3 38.9 ⫾ 0.8 19 360 ⫾ 7840 12 646 ⫾ 6516 75 ⫾ 31 24 ⫾ 12
4 38.8 ⫾ 0.8 15 568 ⫾ 3698 8946 ⫾ 2804 81 ⫾ 18 27 ⫾ 23
ⱖ5 38.8 ⫾ 0.8 18 215 ⫾ 7593 10 015 ⫾ 4387 79 ⫾ 35 21 ⫾ 13
P .76 .20 .08 .02 .64
ESR indicates erythrocyte sedimentation rate; CRP, C-reactive protein.
a C-reactive protein levels were standardized to the upper limit of the normal range for the different laboratories that performed the test; for example, 22 means that the CRP level was 22 times the

upper limit of the range of normality.

first to undertake a detailed examination of whether
delay in instituting appropriate treatment of acute pye-
lonephritis increases the risk of kidney damage. When
cases were stratified according to the duration of clinical
pyelonephritis (determined as the duration of fever) be-
fore the commencement of antibiotic treatment, no sig-
nificant difference in the rates of scarring on DMSA
scans obtained 12 months later was evident (Table 1).
Furthermore, given the widespread belief that infants
and younger children are at increased risk, a separate
analysis of patients between 1 month and 2 years of age
yielded similar results, with no significant difference re-
lated to delay in treatment. The overall rates of scarring
for the various age groups also were independent of the
timing of treatment (Table 2).
The clinical and laboratory indices of inflammation
support similar levels of severity of pyelonephritis in all
groups (Table 3). Only the erythrocyte sedimentation
rate showed a significant increase with duration of ill-
ness (P ⫽ .02); the C-reactive protein levels were con-
sistently elevated and showed no significant change
related to duration of fever. These results provide addi-
tional evidence of delayed treatment in the different
groups. C-reactive protein is an acute-phase reactant
that has a short half-life (19 hours), increasing early
after the onset of inflammation and decreasing rapidly
after its resolution. The erythrocyte sedimentation rate
peaks much less rapidly and may take several days to
decrease, even when the inflammation has been ame-
liorated.26,27
The benefits demonstrated after the initiation of an-
tibiotic treatment were the eradication of infection in all
cases and the time to resolution of fever, which re-
mained relatively constant in all groups (1.6 ⫾ 0.1 days)
(Table 1). No significant difference in the incidence of
scarring was seen in relation to the selection and route of
administration of antibiotics.9 Given these findings, we
recommend prompt treatment of febrile UTIs to facilitate
rapid recovery from the acute illness, although we em-
phasize that we did not find early antibiotic treatment to
be effective in reducing subsequent renal damage. This
should allow a significant reduction in the sense of ur-
gency and consequent anxiety experienced by the family
in the event of suspected relapses or subsequent acute
febrile episodes. It is a common experience of those who
care for young children with UTIs to see the parents rush
to the emergency department or their doctor within
hours after the onset of fever, having received the advice
that early treatment of relapsing pyelonephritis is essen-
tial to avoid renal damage. We think it is possible to
advise a less-urgent approach for children with fever
who appear otherwise well, even if there is a risk of
recurrent UTI.
Numerous studies have addressed the treatment of
acute pyelonephritis in children, comparing different an-
tibiotics and different modes and durations of adminis-
tration. In virtually all of those studies, the outcomes in
terms of kidney damage are similar in the various arms,
leading to the assumption that all treatments are equally
effective in reducing scarring secondary to acute pyelo-
nephritis, which occurs in ⬃30% of cases.
A limitation of this study is not knowing the exact
time of the onset of infection. The closest we were able
to come was to document accurately the onset of symp-
toms, with additional evidence provided by the time
course of the acute-phase reactants.
Despite these limitations, this study reflects accurately
the clinical situation in which a child presents as febrile
and unwell, with symptoms suggesting acute pyelone-
phritis. At such a time, with the inflammatory process
well established, it seems that antibiotics do little to
reduce scarring. Additional research is needed to explore
other avenues of therapy, such as the use of steroids or
other antiinflammatory agents, and to evaluate the role
of genetic factors that may predispose patients to scar
formation.
CONCLUSIONS
Early treatment of acute pyelonephritis in infants and
young children had no significant effect on the incidence
of subsequent renal scarring. Furthermore, there was no
significant difference in the rate of scarring after acute
pyelonephritis when infants and young children were
compared with older children.
ACKNOWLEDGMENTS
Funding was provided by the Region of Veneto (research
project 40/01) and the Association Il Sogno di Stefano
(Stephen’s Dream).

PEDIATRICS Volume 122, Number 3, September 2008 489

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 Participants in IRIS 1 and 2 were as follows: I.
Marella, A. Budini (Adria); L. Marcazzò, S. Bellato (Ar-
zignano); G. Audino, G. Picco (Bassano); P. Colleselli, D.
Scorrano (Belluno); L. Pavanello (Castelfranco); C.
Crivellaro (Chioggia); G. Cattarozzi, M. Pitter, A. Bal-
lan (Dolo/Mirano); F. Rossetti, V. Cannella (Este/Mon-
selice); G. Svaluto-Moreolo, V. Caddia (Feltre); G. Poz-
zan, F. Maschio (Mestre); P. Brisotto, N. Crema, S.
Breseghella (Montebelluna); P. Luxardo, A. Toffolo
(Oderzo); G. Zacchello, G. Montini, L. Murer, C. Carasi,
B. Andreetta, S. Comacchio, L. Rigon, S. Sartori, L. To-
masi, R. Pertile, D. Gobber (epidemiologist), A. Ponzoni
(statistician) (Padua); A. Truini (Piove di Sacco); P. G.
Flora, M. Ranieri (San Donà); R. Dall’Amico, L. Donello
(Thiene); G. Marcer, S. Zanchetta (Soave); M. Del Ma-
jno, M. Gheno (Venice); P. Biban, P. Fortunati (Verona-
Borgo Trento); M. G. Santangelo, O. Gianesini (Vi-
cenza); A. Corsini (Bentivoglio); P. P. Molinari
(Bologna); A. Zucchini (Faenza/Lugo); A. Venturolli
(Forlı̀); L. Serra (Imola); L. Casadio (Ravenna); M. Prin-
cipi (Macerata); M. Pitschiller, W. Cassar (Bolzano); M.
De Marini, G. Crescenzi (Cuneo).
We thank all of the members of the IRIS group who
made the performance of this study possible, and we also
thank Dr Andrea Ponzoni for statistical analysis. We
particularly thank Dr Daniela Gobber (epidemiologist),
who unfortunately passed away 2 years ago.
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 Early Treatment of Acute Pyelonephritis in Children Fails to Reduce Renal
Scarring: Data From the Italian Renal Infection Study Trials
Ian K. Hewitt, Pietro Zucchetta, Luca Rigon, Francesca Maschio, Pier Paolo Molinari,
Lisanna Tomasi, Antonella Toffolo, Luigi Pavanello, Carlo Crivellaro, Stefano Bellato
and Giovanni Montini
Pediatrics 2008;122;486
DOI: 10.1542/peds.2007-2894

Updated Information & including high resolution figures, can be found at:
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References This article cites 24 articles, 7 of which you can access for free at:
http://pediatrics.aappublications.org/content/122/3/486#BIBL
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 Early Treatment of Acute Pyelonephritis in Children Fails to Reduce Renal
Scarring: Data From the Italian Renal Infection Study Trials
Ian K. Hewitt, Pietro Zucchetta, Luca Rigon, Francesca Maschio, Pier Paolo Molinari,
Lisanna Tomasi, Antonella Toffolo, Luigi Pavanello, Carlo Crivellaro, Stefano Bellato
and Giovanni Montini
Pediatrics 2008;122;486
DOI: 10.1542/peds.2007-2894

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/122/3/486

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. Pediatrics is owned, published, and trademarked by
the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright © 2008 by the American Academy of Pediatrics. All rights reserved. Print ISSN:
1073-0397.

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