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aFirst Department of Pediatrics and bThird Department of Pediatrics, P&A Kyriakou Childrens Hospital, Athens, Greece; cSecond Department of Pediatrics, University of
Athens, P&A Kyriakou Childrens Hospital, Athens, Greece
The authors have indicated they have no nancial relationships relevant to this article to disclose.
ABSTRACT
OBJECTIVE. Therapeutic delay has been suggested as the most important factor that is
likely to have an effect on the development of scarring after acute pyelonephritis.
www.pediatrics.org/cgi/doi/10.1542/
However, this opinion has not been supported by prospective studies, so we tested peds.2006-2417
it. doi:10.1542/peds.2006-2417
METHODS. In a prospective clinical study, we evaluated whether the time interval Key Words
urinary tract infection, acute
between the onset of the renal infection and the start of therapy correlates with pyelonephritis, renal scarring,
the development of acute inflammatory changes and the subsequent development vesicoureteral reux
of renal scars, documented by dimercaptosuccinic acid scintigraphy. A total of 278 Abbreviations
infants (153 male and 125 female) aged 0.5 to 12.0 months with their first urinary UTI urinary tract infection
DMSA dimercaptosuccinic acid
tract infection were enrolled in the study. Tc-99mDMSAtechnetium-99m-
dimercaptosuccinic acid
RESULTS. The median time between the onset of infection and the institution of VURvesicoureteral reux
therapy was 2 days (range: 1 8 days). Renal inflammatory changes were docu- CRPC-reactive protein
mented in 57% of the infants. Renal defects were recorded in 41% of the patients Accepted for publication Mar 14, 2007
Address correspondence to Dimitrios Doganis,
treated within the first 24 hours since the onset of fever versus 75% of those MD, 12 Kapetan Petroutsou St, 115 23 Athens,
treated on day 4 and onward. Renal scarring was developed in 51% of the infants Greece. E-mail: doganisd@otenet.gr
with an abnormal scan in the acute phase of infection. The frequency of scarring PEDIATRICS (ISSN Numbers: Print, 0031-4005;
Online, 1098-4275). Copyright 2007 by the
in infants treated early and in those whose treatment was delayed did not differ, American Academy of Pediatrics
suggesting that once acute pyelonephritis has occurred, ultimate renal scarring is
independent of the timing of therapy. Acute inflammatory changes and subse-
quent scarring were more frequent in the presence of vesicoureteral reflux,
especially that which is high grade. However, the difference was not significant,
which suggests that renal damage may be independent of the presence of reflux.
CONCLUSIONS. Early and appropriate treatment of urinary tract infection, especially
during the first 24 hours after the onset of symptoms, diminishes the likelihood of
renal involvement during the acute phase of the infection but does not prevent
scar formation.
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U RINARY TRACT INFECTION (UTI) is among the more
common acute illnesses and the most common
bacterial infection in infants and young children.1 The
Imaging Studies
Renal ultrasonography and renal scintigraphy with Tc-
99mDMSA were performed within 1 to 18 days (median:
infection may be limited to the lower tract or may in- 5 days) of admission to determine anatomic abnormali-
volve the kidney; it may result in permanent renal dam- ties and the presence or absence of acute pyelonephritis,
age and scarring, which may lead to development of respectively. DMSA scan is performed 4 to 6 hours after
hypertension and chronic renal impairment.2 intravenous injection of an age-adjusted dose (minimum
Most cases of the first episode of urinary infection dose: 40 MBq; maximum dose: 100 MBq). Posterior,
occur in the first year of life, and it is generally believed anterior, and lateral posterior oblique planar views were
that infants are more susceptible to development of re- collected for 6 minutes each with a camera equipped
nal parenchymal damage after pyelonephritis than are with a high-resolution low-energy collimator (computer
older children.35 However, recent data have shown no matrix: 256 256). Differential renal function was cal-
culated by using the geometric mean method to com-
difference in age at the time of infection between chil-
pensate for differences in the position of each kidney.
dren who develop scars and those who do not,610 and
Pyelonephritis was defined by the presence of focal or
some studies have even shown that scarring was more
diffuse areas of decreased uptake of DMSA. A second
common in children 1 year of age.1113
cortical scan was performed after 5 to 26 months (me-
Technetium-99m-dimercaptosuccinic acid (Tc-99mDMSA)
dian: 6.5 months) in infants who had a positive DMSA
renal scintigraphy, performed during the acute phase of
scan result in the acute phase of infection. An abnormal
infection, is considered the most sensitive test for the diag- second scan was defined by the presence of decreased
nosis of renal involvement and the subsequent develop- uptake of DMSA associated with loss of the contour of
ment of renal scarring.14 Among several risk factors the kidney or by the presence of cortical thinning.
likely to have an effect on the development of renal Voiding cystourethrogram was performed in the ma-
damage during the acute episode of renal infection, the jority of cases while the child was in the hospital before
time between the onset of symptoms of the infection and discharge.23,24 Vesicoureteral reflux (VUR) was graded
the beginning of the appropriate therapy is considered according to the classification proposed by the Interna-
by many experts to be 1 of the most significant.3,1520 This tional Reflux Study Committee.25 Children who were
opinion is supported by experimental studies, which found to have VUR were placed on chemoprophylaxis
demonstrated a correlation between the duration of in- with trimethoprim-sulfamethoxazole (2 mg/kg for the
fection until the start of treatment and the extent of trimethoprim component). Infants 2 months of age
renal damage.21,22 On the other hand, this opinion has were given prophylaxis with cefuroxime-axetil (10 mg/
not been demonstrated by prospective clinical studies.9 kg).
The aim of our prospective study was to correlate the
findings of the Tc-99mDMSA renal scintigraphy with the Laboratory Tests
time passed since the onset of fever until the commence- The laboratory tests in these patients at the time of
ment of therapy in infants with a first episode of UTI. admission included obtaining a white blood cell count
and differential and the C-reactive protein (CRP) level.
METHODS Statistics
Enrollment and Eligibility Criteria 2 test, Fishers exact test, and the nonparametric Mann-
We undertook a 5-year (2000 2005) prospective study Whitney test were used for statistical analysis. A P value
in a cohort of 278 children 12 months of age who were of .05 was considered to indicate statistical significance.
admitted to the hospital with a first documented episode
of UTI. Children were eligible to be included in the study RESULTS
if they had a temperature of 38C and a positive cul- Patient Characteristics
ture of urine collected by suprapubic puncture. The A total of 278 children,153 boys and 125 girls, were
growth of any number of colonies of Gram-negative enrolled in the study. The median age was 3.5 months
bacilli was considered as positive. All of the children (range: 0.512.0 months). Of the 278 children, 128 (96
were treated with antibiotics immediately after the urine boys and 32 girls) were 3 months old, 80 (34 boys and
and blood samples were obtained. Patients were treated 46 girls) were 3 to 6 months old, and 70 (23 boys and 47
with intravenous antibiotics given until they had been girls) were 6 months old.
afebrile for 24 to 36 hours. An oral antibiotic was pro-
vided to complete a 10- to 14-day course. The time Treatment Delay and Timing of Scintigraphy
between the onset of fever and the institution of therapy The median time between the onset of fever and the
was recorded. institution of treatment was 2 days (range: 1 8 days).
FIGURE 1
DMSA results in the acute phase and day of treatment.
e924 DOGANIS et al
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FIGURE 2
DMSA results in the acute phase and day of treatment in infants
younger than 3 months.
FIGURE 3
DMSA results in the acute phase and day of treatment in infants
older than 3 months.
TABLE 1 The Relationship Between the First DMSA Scan Findings TABLE 2 The Relationship Between the Second DMSA Scan
and the Presence and Grade of VUR Findings and the Presence and Grade of VUR
Variable Patients Without Patients With VUR Total Variable Patients Without Patients With VUR Total
VUR VUR
Grades Grades Grades Grades
I -III IV-V I-III IV-V
Normal DMSA scan result 93 (45.8) 20 (38.5) 2 (14.3) 115 (42.8) Normal DMSA scan result 27 (56.2) 7 (35.0) 3 (37.5) 37 (48.7)
Abnormal DMSA scan result 110 (54.2) 32 (61.5) 12 (85.7) 154 (57.2) Abnormal DMSA scan result 21 (43.8) 13 (65.0) 5 (62.5) 39 (51.3)
Total 203 (100.0) 52 (100.0) 14 (100.0) 269 (100.0) Total 48 (100.0) 20 (100.0) 8 (100.0) 76 (100.0)
Data are number (percentage) of infants. Data are number (percentage) of infants.
significance. The relationship between the presence of terial pathogens in 5 infants. No correlation between
VUR and the results of the follow-up scan are shown on any type of bacteria and renal involvement was doc-
Table 2. umented.
Elevated temperature, leucocytosis, increased neutro-
Clinical and Laboratory Findings and Renal Involvement phils, and CRP level were correlated with the presence of
Escherichia coli was isolated from the urine of 242 infants, an abnormal scan during the acute infection (Table 3).
Proteus mirabilis from 4, Klebsiella spp from 18, Citrobacter On the other hand, no significant differences were noted
spp from 1, Enterobacter spp from 5, Pseudomonas spp comparing maximum temperature, white blood cell
from 1, Enterococcus spp from 1, other Gram-negative count, neutrophils, CRP level, and development of scar-
bacterial pathogens from 1, and 2 Gram-negative bac- ring.
e926 DOGANIS et al
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are in agreement with the findings of our study. Others ment but not with permanent renal damage. The pres-
have not found a correlation between treatment delay ence of VUR or grade of reflux does not increase the
time and early DMSA findings. In one study, no differ- incidence of renal involvement and scarring.
ence in the frequency of DMSA abnormalities was noted
between those patients treated within 2 days since the
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e928 DOGANIS et al
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Does Early Treatment of Urinary Tract Infection Prevent Renal Damage?
Dimitrios Doganis, Konstantinos Siafas, Myrsini Mavrikou, George Issaris, Anna
Martirosova, Grigorios Perperidis, Andreas Konstantopoulos and Konstantinos
Sinaniotis
Pediatrics 2007;120;e922-e928; originally published online Sep 17, 2007;
DOI: 10.1542/peds.2006-2417
Updated Information including high-resolution figures, can be found at:
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