ORIGINAL ARTICLE

Screening high-grade vesicoureteral reflux in young infants

with a febrile urinary tract infection
Jeng-Daw Tsai & Chang-Ting Huang & Pei-Yi Lin &
Jui-Hsing Chang & Ming-Dar Lee & Fu-Yuan Huang &
Bing-Fu Shih & Han-Yang Hung & Chyong-Hsin Hsu &
Hsin-An Kao & Chun-Chen Lin
Received: 25 October 2011 / Revised: 3 January 2012 / Accepted: 4 January 2012 / Published online: 1 March 2012
#IPNA 2012
Abstract
Background The lack of good evidence for improved out-
comes in children and young infants with febrile urinary tract
infection (UTI) after aggressive treatment for vesicoureteral
reflux (VUR) has raised doubts regarding the need for routine
voiding cystourethrography (VCUG), and the appropriate
imaging evaluation in these children remains controversial.
Objectives This prospective study aimed to determine
whether abnormalities found on acute dimercaptosuccinic
acid (DMSA) scan and ultrasound (US) can help indicate
the necessity of voiding cystourethrography (VCUG) in
young infants.
Methods For 3.5 years, all infants younger than 3 months
presenting with first febrile UTI were prospectively studied.
All infants were hospitalized and investigated using US
(<3 days after admission), DMSA scan (<5 days after ad-
mission), and VCUG (710 days after antibiotic treatment)
after diagnosis. The association among findings of US,
DMSA scan, and VCUG were evaluated.
Results From 220 infants, there were abnormal results in
136 (61.8%) US and in 111 (50.5%) DMSA scans. By US,
ten infants (4.5%) with abscess or structural abnormalities
other than VUR were diagnosed. High-grade (IIIV) VUR
was present in 39 patients (17.7%). The sensitivities for
high-grade VUR of renal US alone (76.9%) or DMSA scan
alone (82.1%) were not as good as that of the OR rule
strategy, which had 92.3% sensitivity and 94.3% negative
predictive value.
Conclusions To screen high-grade VUR in young infants
with febrile UTI, US and acute DMSA scan could be per-
formed first. VCUG is only indicated when abnormalities
are apparent on either US or DMSA scan or both.
Keywords Dimercaptosuccinic acid
.
Ultrasound
.
Urinary
tract infections
.
Vesicoureteral reflux
.
Infant
Introduction
The proper approach to imaging evaluation in children with
febrile urinary tract infection (UTI) remains controversial,
especially in young infants. Given the good prognosis for
most children with vesicoureteral reflux (VUR) and the lack
of good evidence for improved outcomes after aggressive
treatment of VUR, doubts have been raised as to the neces-
sity of routine voiding cystourethrography (VCUG) [1].
Moreover, VCUG is an invasive procedure with radiation
burden, discomfort due to the need for catheterization, and a
risk of iatrogenic infection. There is a trend toward using
less invasive methods to evaluate children with UTI first and
J.-D. Tsai
:
C.-T. Huang
:
J.-H. Chang
:
M.-D. Lee
:
F.-Y. Huang
:
H.-Y. Hung
:
C.-H. Hsu
:
H.-A. Kao
:
C.-C. Lin (*)
Department of Pediatrics, Mackay Memorial Hospital,
No 92, Section 2, Chungshan North Road,
Taipei, Taiwan
e-mail: chunchenlin@yahoo.com.tw
J.-D. Tsai
:
F.-Y. Huang
Department of Pediatrics, Taipei Medical University,
Taipei, Taiwan
P.-Y. Lin
Department of Pediatrics, Shuang Ho Hospital,
Taipei Medical University,
Taipei, Taiwan
J.-H. Chang
:
C.-C. Lin
Mackay Medicine, Nursing and Management College,
Taipei, Taiwan
B.-F. Shih
Division of Nuclear Medicine, Mackay Memorial Hospital,
Taipei, Taiwan
Pediatr Nephrol (2012) 27:955963
DOI 10.1007/s00467-012-2104-1
to perform VCUG more selectively [24]. Recent meta-
analyses of published data shows that low-grade VUR is
of low clinical significance and does not need to be diag-
nosed and treated [5]. Furthermore, according to the meta-
analysis of new American Urological Association (AUA)
guidelines, the risk of acute pyelonephritis (APN) and scar-
ring is considered higher in younger children with grades
IIIV VUR [6]. New guidelines from the American Acade-
my of Pediatrics (AAP) recommend VCUG is indicated if
ultrasound (US) reveals hydronephrosis, scarring, or other
findings that would suggest either high-grade VUR or ob-
structive uropathy, recurrent UTI, as well as in atypical or
complex clinical circumstances [7]. The recommendation
not to routinely perform a VCUG is consistent with a
guideline proposed by the National Institute for Health and
Clinical Excellence (NICE) [8].
Several studies have advocated the concept of a top-
down approach to the evaluation of children with UTI and
a reduction in the number of VCUG performed. The advo-
cated approach begins with a dimercaptosuccinic acid
(DMSA) scan with or without renal US, with VCUG per-
formed when the DMSA scan or US is abnormal or there is
subsequent recurrent UTI [916]. To screen high-grade
VUR, our previous study shows that VCUG can be per-
formed when abnormalities are apparent on either US or
DMSA scan in children aged 2 months to 2 years [13]. This
prospective study aimed to determine whether or not abnor-
malities found on US and DMSA also can help guide the use
of VCUG in young infants.
Patients and methods
During a 3.5-year period, from January 2007 to June 2010,
all infants <3 months old presenting with first febrile UTI
were investigated prospectively. All patients were hospitalized
in the Newborn Center of Mackay Memorial Hospital. Fever
was defined as body temperature >38C. All urine cultures
were obtained by suprapubic aspiration or bladder catheteri-
zation; positive results were defined as >50,000 CFU/ml of a
uropathogen [7]. Babies with known genitourinary tract
anomalies, detected by prenatal US, and history of UTI or
neurologic disease were not included in the study. Our re-
search was reviewed and approved by Institutional Review
Board. Informed consent was obtained from parents after they
were informed of the aims, potential risks, and benefits of
imaging studies. All infants were initially treated with a com-
bination of ampicillin and gentamicin i.v. after admission.
Once initial result of urine culture were available in 2448 h
and UTI was diagnosed, US and DMSA scan were arranged
and performed immediately. US, DMSA scan, and VCUG
were performed and analyzed by independent examiners who
were blinded to the results of other tests. Effective antibiotics
i.v. were continued for at least 7 days, followed by antibiotics
orally based on antibiotic sensitivity testing. The overall du-
ration of treatment was 14 days.
Bladder and renal US was performed within 3 days of
admission by an experienced pediatric nephrologist. All
abnormal US findings were recorded, including dilatation
of the pelvis, calyx, ureter (any dilatation of ureter seen on
US) or posterior urethra, fluctuating renal pelvis (size of the
renal pelvis changing by >4 mm during the course of renal
sonograms) [17], thickened pelvic wall (circumferential
hypoechoic rim delineated on each side by thin hyperechoic
lines, the rim being thicker than 0.8 mm) [18], ureter, or
bladder (>3 mm in a full or 5 mm in an empty bladder) [19],
swelling or thinning of renal parenchyma, diffuse or focal
increased renal echogenicity with absence of corticomedul-
lary differentiation, renal abscess, and signs of renal hypo-
dysplasia (i.e., small kidney, thinned or hyperechoic cortex,
and cortical cysts) [20], or a duplicated collecting system.
Renal length was regularly measured from the back, and the
reference value was based on normograms described by
Vujic et al. [21]. Renal length >2 standard deviation scores
(SDS) or <2 SDS was considered abnormal. Hydroneph-
rosis was graded according to the definition of the Society of
Fetal Urology (grades IIV) [22].
A DMSA scan was performed within 5 days after admis-
sion and was considered normal when homogenous uptake
of the isotope was evident throughout the kidneys and the
renal contour was preserved. APN was diagnosed if there
was a focal or multiple areas of diminished isotope uptake
with preserved renal contour or when the kidney was en-
larged with diffuse decrease in uptake. Renal cortical scars
were reported when there were defects in uptake associated
with cortical loss and decreased renal volume. A small
kidney with diffusely decreased isotope uptake and de-
creased differential renal function was reported as renal
hypodysplasia [23]. A VCUG was performed 710 days
after appropriate antibiotic treatment and was read by a
pediatric nephrologist. VUR was graded according to rec-
ommendations of the International Reflux Study in Chil-
dren. Children with grades IIIV reflux were defined as
high-grade VUR. In infants with bilateral VUR, the higher
grade of the two ureters was recorded. Prophylactic anti-
biotics were given in infants with high-grade VUR.
To assess the usefulness of imaging studies in screening
for VUR, which indicated the need for VCUG, four
approaches were compared: US alone, DMSA scan alone,
the OR rule, and the AND rule. We analyzed the com-
bined results of US and DMSA scan in parallel according to
Weinstein et al. [24]. The OR rule strategy was defined as
the routine performance of both US and DMSA scan in all
children with first febrile UTI. An abnormality on either
study or on both constituted an indication for VCUG. The
AND rule strategy was defined as performance of VCUG
956 Pediatr Nephrol (2012) 27:955963
only if both US and DMSA scan were abnormal but VCUG
was not performed if either study was normal. The diagnos-
tic significance of renal US, DMSA scan, OR rule, and
AND rule strategies in relation to the presence of all (IV)
or high-grade VUR was assessed by odds ratios (ORs) using
logistic regression analysis. Sensitivity, specificity, positive
(PNV) and negative (NPV) predictive values, and positive
or negative likelihood ratios (LR) for all and high-grade
VUR of these methods were calculated.
Results
In this study, 231 infants were eligible and prospectively
studied. Urine specimens were collected by suprapubic as-
piration in 150 (65%) infants and by catheterization in the
remaining 81 (35%). The most common causative agent was
Escherichia coli, affecting 196 (89.1%) patients. US was
performed in all infants. Eleven patients were excluded.
They did not receive DMSA or VCUG (including four
missed DMSA and seven missed VCUG) because of paren-
tal concern on the invasive nature or radiation exposure. The
overall adherence to the protocol was 95.2%. There were
220 infants (167 boys, 53 girls; male to female ratio 3.2:1.0)
with mean age of 60.222.8 (range 690) days (Fig. 1). All
male infants were uncircumcised.
VUR was diagnosed in 60 patients (27.3%; 46 boys, 14
girls) (Table 1). High-grade VUR was present in 39 patients
(17.7%, 31 boys, 8 girls). The incidence of VUR did not
significantly differ between boys and girls (p00.872). Of
220 infants, 136 (61.8%) US results and 111 (50.5%)
DMSA scan results were abnormal (Table 2). The calculated
sensitivity, specificity, PPV, NPV, and positive or negative
LRs for all and high-grade VUR of the four methods are
shown in Table 3.
Abnormal US findings include hydronephrosis or caly-
ceoectasia in 86 (39.1%, four grade III; 82 grades III
hydronephrosis), focal, multifocal, or diffuse APN in 53
(24.1%), thickened bladder wall in six, cyclic dilatation of
the collecting system in six, thickened pelvic wall in four,
and hydroureter in eight infants. Moreover, by US, ten
patients (4.5%) had severe infections or congenital urinary
tract anomalies other than VUR, including renal abscess (1),
duplex collecting system (4), ureteropelvic junction obstruc-
tion (2), posterior urethral valves (1), adrenal hemorrhage
(1), and ectopic kidney (1). These patients all needed further
imaging studies or management. Renal hypodysplasia was
diagnosed unilaterally in five boys (2.3%) by US and con-
firmed by DMSA scan. Their differential renal functions
were all <30%, with a mean of 20.8% (range 925%); four
of the five had associated high-grade VUR. In infants with
abnormal US, 40 had VUR and 30 had high-grade VUR.
However, 20 with VUR and nine with high-grade VUR had
normal US findings and would have been missed if US was
the only screening test. Sensitivity, specificity, NPV, and
diagnostic OR of US for high-grade VUR were 76.9 %
(95% CI, 60.388.3%), 41.4% (95% CI, 34.249.0%),
89.3% (95% CI, 80.294.7%), and 2.36 (95% CI, 1.06
5.26), respectively (Tables 2 and 3). Of the 111 children
with abnormal DMSA scan results, 41 had VUR and 32 had
high-grade VUR. However, 19 with all-grade VUR and
seven with high-grade VUR had normal DMSA scan
results. Thus, sensitivity, specificity, NPV, and diagnostic
OR of DMSA scan for high-grade VUR were 82.1%, (95%
CI, 65.991.9%), 56.4% (95% CI, 48.863.6%), 93.6%
(95% CI, 86.897.1%), and 5.90 (95% CI, 2.4814.07),
respectively (Tables 2 and 3).
For OR rule strategy, 167 infants (75.9%) with abnormal
findings would have undergone VCUG, 48 of whom had
VUR and 36 had high-grade VUR. Of the 53 without
abnormalities on either test, 12 had VUR, including three
with high-grade VUR. For detecting all-grade VUR, the OR
rule strategy had only 80.0% (95% CI, 67.388.8%) sensi-
tivity, 25.5% (95% CI, 19.233.2%) specificity, 77.4%
(95% CI, 63.587.2%) NPV, and 1.38 (95% CI, 0.67
2.85) diagnostic OR. Therefore, the OR rule strategy was
not good enough for detecting all-grade VUR. However, for
detecting high-grade VUR, sensitivity, NPV, and diagnostic
OR of OR rule strategy were up to 92.3%, (95% CI, 78.0
98.0%), 94.3% (95% CI, 83.498.5%), and 4.58 (95% CI,
1.3515.5%), respectively (Tables 2 and 3). Three infants
had high-grade VUR but normal US and DMSA scan find-
ings. They had bilateral grade IV, bilateral grade III, and
right grade III VUR, respectively, and were all treated with
prophylactic antibiotics without breakthrough infection in
the 1-year follow-up. All three had complete resolution of
VUR 1 year later, with no scar noted on follow-up us.
Among the 70 infants with lesions on DMSA but no
VUR, 15 (21.4%) had persistent lesions during follow-up,
and 16 (39.0%) of 41 infants with abnormal DMSA and
VUR had scar after follow-up 6 months later.
In contrast, using the AND rule strategy, specificity
increased to 70.2% (95% CI, 62.976.6%), PPV to 32.5
(95% CI, 22.744.0%), and diagnostic OR to 4.70 (95%
CI, 2.259.84). However, sensitivity decreased to 66.7%
(95% CI, 50.780.4%) and NPV to 90.7% (95% CI, 84.3
94.8%). Although only 80 infants (36.4%) would have
undergone VCUG, 13 (33.3%) with high-grade VUR
would have been missed if the AND rule strategy was
used.
Discussion
Several reports suggest that acute DMSA scan with or
without renal US may be used as screening test to identify
Pediatr Nephrol (2012) 27:955963 957
high-grade VUR. Table 4 summarizes published data as
regards screening high-grade VUR by DMSA scan with or
without renal US [916]. Results are quite variable, with
sensitivity ranging from 29% to 100% in different studies
because of heterogeneous study populations and designs for
evaluation. The multiple determinant factors may include,
but are not limited to, retrospective or prospective nature of
the study; age, sex, and number of patients; study duration;
different races; inclusion criteria (febrile or afebrile UTI);
definition of fever; circumcision status in boys; timing of
US and DMSA examination; methodology and interobserv-
er variability in interpreting renal US or DMSA scan; blad-
der dysfunction; and performance of prenatal US. Our
hospital provides inpatient care to all febrile infants
Infants <3 months with a first febrile UTI (>38
o
C),
without known genitourinary tract anomalies and
history of UTI or neurologic disease, N = 231
Infants who did not complete
the initial imaging studies (US
and DMSA) -missing US: N = 0
; missing DMSA: N = 4
Infants who complete the renal US (<3 days after
admission) and DMSA (<5 days after admission)
N = 227
Infants who missed VCUG (7-10
days after antibiotic treatment)
N = 7
Infants who complete the diagnostic
work-up (US, DMSA, VCUG)
N = 220 (adherence = 95.2%)
Grade 3-5 VUR
N = 39
Grade 1-2 VUR or no VUR
N = 181
Normal US
and DMSA
N = 3
Abnormal US
and DMSA
N = 26
Either abnormal US
(normal DMSA) or
DMSA (normal US)
N = 10
Normal US
and DMSA
N = 50
Abnormal US
and DMSA
N = 54
Either abnormal US
(normal DMSA) or
DMSA (normal US)
N = 77
Fig. 1 Adherence to the protocol for imaging studies in young infants with a first febrile urinary tract infection. US ultrasound, DMSA
dimercaptosuccinic acid scan, VCUG voiding cystourethrography, VUR vesicoureteral reflux, UTI urinary tract infection
958 Pediatr Nephrol (2012) 27:955963
aged <3 months who are referred by pediatricians or
seen at the clinic or emergency room. As such, our
study sample represents an unbiased general population
of young infants with febrile UTI rather than those too
sick to be treated as outpatients. The bias is reduced by
solid and consistent criteria and proper study design and
execution (overall 95.2% adherence).
Clinical, laboratory, and US parameters are of no help for
differentiating between upper and lower UTI in young chil-
dren [25]. DMSA scan is the gold standard for diagnosing
APN and renal scarring. An acute DMSA scan is preferred
for infants with febrile UTI because they are more likely to
suffer more significant morbidity with APN and subsequent
renal scarring than are older children,and are less able to
communicate their symptoms, leading to a potential delay in
diagnosis [6]. Initially, several reports showed that normal
acute DMSA scan rules out the possibility of high-grade
VUR and can therefore replace VCUG [911]. In our study,
abnormal DMSA had a sixfold higher risk for high-grade
VUR. However, it has been shown that DMSA has limited
overall ability in identifying high-grade VUR and replacing
VCUG for evaluating children with febrile UTI [1216].
The meta-analysis study shows the pooled sensitivity and
specificity of DMSA scan were only 79% and 53%, respec-
tively, for the patient-based analysis [26]. Data are quite
similar to those in our study, with sensitivity 82.1% and
specificity 56.1%.
For a prospective design and similar presentation, our
study has a higher frequency of abnormal DMSA than do
Fouzass results (50.5% vs. 39.9%) at a younger age (mean
age 2 vs. 5 months) and earlier performance of DMSA
(<5 days after admission vs. 714 days after diagnosis)
[15]. Stokland et al. show that the rate of positive DMSA
results rapidly decreases by 50% during the initial 14 days
after start of antibiotic treatment [27]. We suggest that for
increased identification of APN, DMSA should be per-
formed as soon as possible. This could explain our higher
sensitivity (82.1%) of DMSA scan for detecting high-grade
VUR than Foutzass (69.6%). A prospective study reported
by Siomou shows only 29% sensitivity of DMSA scan in
predicting high-grade VUR [12]. However, they included
neonates with nonspecific symptoms, and only 28% of the
patients had febrile UTI. Because most neonates do not have
APN, abnormal DMSA is found in only 19% of renal units,
which, of course, results in low sensitivity for predicting
high-grade VUR (Table 4).
Although DMSA scan is not recommended as part of
routine evaluation by AAP guidelines, it is listed as an
option by AUA guidelines [6, 7]. In our study, 70 infants
had lesions on DMSA but no VUR on VCUG. During
follow-up 6 months later, 15 of them (21.4%) finally had
persistent lesions. This number is almost equal to the num-
ber of infants with VUR and persistent scar (16 of 41),
which means that about half of infants with scar will be
missed if DMSA is not performed. Although identifying
Table 1 Findings on voiding cystourethrography (VCUG) in young
infants with first febrile urinary tract infection (n0220)
Finding Number of children (%)
Total Boys Girls
No VUR 160 (72.7%) 121 39
VUR 60 (27.3%) 46 14
Grade I 4 (1.8%) 3 1
Grade II 17 (7.7%) 12 5
Grade III 21 (9.5%) 13 8
Grade IV 13 (5.9%) 13 0
Grade V 5 (2.3%) 5 0
VUR vesicoureteral reflux
Table 2 Usefulness of renal
ultrasound (US), dimercaptosuc-
cinic acid (DMSA) scan, OR
rule, and AND rule strategies
for detecting vesicoureteral
reflux (VUR) and high-grade
VUR
OR odds ratio, CI confidence in-
terval, DMSA dimercaptosuccinic
acid
Test All-grade VUR High-grade VUR
Absent Present OR (95% CI) Absent Present OR (95% CI)
Renal ultrasound 1.33 (0.72-2.49) 2.36 (1.06-5.26)
Abnormal 96 40 106 30
Normal 64 20 75 9
DMSA scan 2.77 (1.48-5.20) 5.90 (2.48-14.07)
Abnormal 70 41 79 32
Normal 90 19 102 7
OR rule 1.38 (0.67-2.85) 4.58 (1.35-15.55)
Abnormal 119 48 131 36
Normal 41 12 50 3
AND rule 2.94 (1.59-5.42) 4.70 (2.25-9.84)
Abnormal 47 33 54 26
Normal 113 27 127 13
Pediatr Nephrol (2012) 27:955963 959
high-grade VUR may be important, VUR is not necessary
for the development of scarring. An acute DMSA scan can
better signify risk for subsequent scarring irrespective of the
presence of VUR.
The noninvasive nature, lack of radiation, good anatomic
demonstration of the entire urinary system, and low cost of
US make it an ideal tool for initial screening for anatomic
abnormalities in infants with UTI [68, 28]. However, with
the widespread use of antenatal US, the likelihood of an
abnormal US after UTI is decreased [29]. In our country, all
pregnant women are allowed to have routine screening by
prenatal US around the 22nd to 23rd week of pregnancy
with support of National Health Insurance. However, seri-
ous complication (abscess) or anatomic abnormalities other
than VUR that may affect patient management are still
detected in 4.5% of patients. We agree with the recommen-
dations of Giorgi et al., who also reported unexpected ab-
normalities significantly altering management were
diagnosed in 4.4% infants with routine US scanning [30].
For high-grade VUR, the rate of US detection ranges from
22% when only the dilated collecting system is defined as
abnormal [29], to 67% [13] and 86% [20] when other
abnormal findings potentially associated with VUR (caly-
ceal or ureteral dilatation, renal hypodysplasia, thickened
bladder or pelvis wall, fluctuating renal pelvis) are included.
Our previous study with a large sample size (699 children)
showed renal hypodysplasia, fluctuating renal pelvis, and
hydroureter were the most reliable clues for predicting high-
grade VUR [13]. By looking for any of these findings,
sensitivity and specificity of US for detecting high-grade
VUR in this study is 76.9% and 41.4%. However, when
mild urinary tract dilatation was considered abnormal, al-
though many patients with high-grade VUR fall into the
category of abnormal US, we also included infants with
pelvis dilatation produced by acute infection [7] and tran-
sient hydronephrosis caused by ureteric folds [22]. This
could explain the high sensitivity in our study, and the
tradeoff is poor specificity and PPV.
In this study, both US and DMSA scan have poorer
sensitivity (76.9% and 82.1%, respectively) for screening
high-grade VUR, but US might be better at detecting ab-
scess or other anatomic abnormalities, whereas DMSA is
better at identifying patients at risk for renal scarring. The
OR rule strategy results in higher sensitivity (92.3%) and
NPV (94.3%), although specificity (27.6%) and positive
(1.28) and negative (0.28) LRs are not good enough. In
contrast, the AND rule strategy would privilege specificity
(70.2%) and PPV (32.5%) at the cost of decreased sensitiv-
ity (66.7%) and NPV (90.7%). If high-grade VUR is con-
sidered an important prognostic factor and should be
identified, screening for high-grade VUR puts a premium
on sensitivity rather than on specificity. With a high sensi-
tivity and NPV, the OR rule strategy may be used as a good T
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9
5
%
C
I
)
(
9
5
%
C
I
)
(
9
5
%
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I
)
(
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5
%
C
I
)
S
e
n
s
i
t
i
v
i
t
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,
%
6
6
.
7
(
5
3
.
2

7
8
.
0
)
6
8
.
3
(
5
4
.
9

7
9
.
4
)
8
0
.
0
(
6
7
.
3

8
8
.
8
)
5
5
.
0
(
4
1
.
7

6
7
.
7
)
7
6
.
9
(
6
0
.
3

8
8
.
3
)
8
2
.
1
(
6
5
.
9

9
1
.
9
)
9
2
.
3
(
7
8
.
0

9
8
.
0
)
6
6
.
7
(
5
0
.
7

8
0
.
4
)
S
p
e
c
i
f
i
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i
t
y
,
%
4
0
.
0
(
3
2
.
4

4
8
.
1
)
5
6
.
3
(
4
8
.
2

6
4
.
0
)
2
5
.
5
(
1
9
.
2

3
3
.
2
)
7
0
.
6
(
6
2
.
8

7
7
.
4
)
4
1
.
4
(
3
4
.
2

4
9
.
0
)
5
6
.
4
(
4
8
.
8

6
3
.
6
)
2
7
.
6
(
2
1
.
4

3
4
.
8
)
7
0
.
2
(
6
2
.
9

7
6
.
6
)
P
P
V
,
%
2
9
.
4
(
2
2
.
1

3
7
.
9
)
3
6
.
9
(
2
8
.
1

4
6
.
7
)
2
8
.
7
(
2
2
.
1

3
6
.
3
)
4
1
.
3
(
3
0
.
5

5
2
.
8
)
2
2
.
1
(
1
5
.
6

3
0
.
1
)
2
8
.
8
(
2
0
.
8

3
8
.
3
)
2
1
.
6
(
1
5
.
7

2
8
.
7
)
3
2
.
5
(
2
2
.
7

4
4
.
0
)
N
P
V
,
%
7
6
.
2
(
6
5
.
4

8
4
.
5
)
8
2
.
6
(
7
3
.
9

8
8
.
9
)
7
7
.
4
(
6
3
.
5

8
7
.
2
)
8
0
.
7
(
7
3
.
0

8
6
.
7
)
8
9
.
3
(
8
0
.
2

9
4
.
7
)
9
3
.
6
(
8
6
.
8

9
7
.
1
)
9
4
.
3
(
8
3
.
4

9
8
.
5
)
9
0
.
7
(
8
4
.
3

9
4
.
8
)
P
o
s
i
t
i
v
e
L
R
1
.
1
1
(
0
.
8
9

1
.
3
8
)
1
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5
6
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1
.
2
2

2
.
0
0
)
1
.
0
8
(
0
.
9
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1
.
2
6
)
1
.
8
7
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1
.
3
4

2
.
6
1
)
1
.
3
1
(
1
.
0
6

1
.
6
2
)
1
.
8
8
(
1
.
5
1

2
.
3
5
)
1
.
2
8
(
1
.
1
2

1
.
4
5
)
2
.
2
3
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1
.
6
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3
.
0
6
)
N
e
g
a
t
i
v
e
L
R
0
.
8
3
(
0
.
5
7

1
.
2
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)
0
.
5
6
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0
.
3
8

0
.
8
2
)
0
.
7
8
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0
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4
5

1
.
3
4
)
0
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6
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0
.
4
8

0
.
8
5
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0
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5
6
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0
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3
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1
.
0
0
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.
3
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0
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1
6

0
.
6
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.
2
8
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0
.
0
9

0
.
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3
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0
.
7
4
)
C
I
c
o
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f
i
d
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c
e
i
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t
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r
v
a
l
,
P
P
V
p
o
s
i
t
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p
r
e
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t
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l
u
e
,
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P
V
n
e
g
a
t
i
v
e
p
r
e
d
i
c
t
i
v
e
v
a
l
u
e
,
L
R
l
i
k
e
l
i
h
o
o
d
r
a
t
i
o
960 Pediatr Nephrol (2012) 27:955963
T
a
b
l
e
4
R
e
p
o
r
t
e
d
s
t
u
d
i
e
s
u
s
i
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d
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r
c
a
p
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c
c
i
n
i
c
a
c
i
d
(
D
M
S
A
)
s
c
a
n
w
i
t
h
/
w
i
t
h
o
u
t
r
e
n
a
l
u
l
t
r
a
s
o
u
n
d
(
U
S
)
f
o
r
e
v
a
l
u
a
t
i
n
g
h
i
g
h
-
g
r
a
d
e
(
I
I
I

V
)
v
e
s
i
c
o
u
r
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t
e
r
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r
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f
l
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(
V
U
R
)
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t
u
d
y
(
y
e
a
r
)
P
o
p
u
l
a
t
i
o
n
(
n
)
V
U
R
i
n
c
i
d
e
n
c
e
(
%
)
M
e
t
h
o
d
o
f
s
c
r
e
e
n
i
n
g
S
e
n
s
i
t
i
v
i
t
y
(
%
)
S
p
e
c
i
f
i
c
i
t
y
(
%
)
P
P
V
(
%
)
N
P
V
(
%
)
R
e
d
u
c
e
d
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m
b
e
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f
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,
%
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e
p
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a
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e
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C
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G
1
.
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a
n
s
s
o
n
e
t
a
l
.
[
9
]
3
0
3
(
<
2
Y
/
O
)
i
n
6
Y
A
l
l
g
r
a
d
e
:
2
6
.
4
%
D
M
S
A
s
c
a
n
(
2
.
2
M
)
8
0
.
6
5
2
.
4
1
8
.
6
9
5
.
2
4
9
Y
e
s
r
e
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r
o
s
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t
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v
e
-
2
0
0
4
f
e
v
e
r
(
>
3
8
.
5

C
)
:
8
2
%
H
i
g
h
-
g
r
a
d
e
:
1
1
.
9
%
2
.
P
r
e
d
a
e
t
a
l
.
[
1
0
]
2
9
0
(
<
1
Y
/
O
)
i
n
3
Y
A
l
l
g
r
a
d
e
:
1
7
.
9
%
D
M
S
A
s
c
a
n
(
5
d
a
y
s
a
f
t
e
r
a
d
m
i
s
s
i
o
n
)
9
6
.
2
4
6
.
8
1
7
.
4
9
9
.
3
4
9
.
0
Y
e
s
p
r
o
s
p
e
c
t
i
v
-
2
0
0
7
f
e
v
e
r
(
>
3
8
.
5

C
)
:
7
9
%
H
i
g
h
-
g
r
a
d
e
:
9
.
3
%
3
.
T
s
e
n
g
e
t
a
l
.
[
1
1
]
1
4
2
(
<
2
Y
/
O
)
i
n
1
0
Y
A
l
l
g
r
a
d
e
:
2
9
.
6
%
D
M
S
A
s
c
a
n
(
<
2
d
a
y
s
a
f
t
e
r
d
i
a
g
n
o
s
i
s
)
1
0
0
3
4
.
0
2
1
.
0
1
0
0
3
0
.
3
Y
e
s
r
e
t
r
o
s
p
e
c
t
i
v
e
-
2
0
0
7
f
e
v
e
r
(
d
e
f
i
n
i
t
i
o
n
?
)
H
i
g
h
-
g
r
a
d
e
:
1
4
.
8
%
4
.
S
i
o
m
o
u
e
t
a
l
.
[
1
2
]
7
2
(
<
1
M
/
O
)
i
n
4
Y
A
l
l
g
r
a
d
e
:
2
2
%
D
M
S
A
s
c
a
n
(
<
3
d
a
y
s
a
f
t
e
r
d
i
a
g
n
o
s
i
s
)
2
9
.
0
8
2
.
0
1
8
.
0
8
9
.
0
8
1
.
0
N
o
p
r
o
s
p
e
c
t
i
v
e
-
2
0
0
9
f
e
v
e
r
:
2
8
%
H
i
g
h
-
g
r
a
d
e
:
1
3
%
(
L
o
w
s
e
n
s
i
t
i
v
i
t
y
)
N
o
f
e
v
e
r
:
7
2
%
5
.
L
e
e
e
t
a
l
.
[
1
3
]
6
9
9
(
2
M
-
2
Y
/
O
)
i
n
4
Y
A
l
l
g
r
a
d
e
:
2
9
.
5
%
D
M
S
A
s
c
a
n
(
<
5
d
a
y
s
a
f
t
e
r
a
d
m
i
s
s
i
o
n
)
a
n
d
r
e
n
a
l
u
l
t
r
a
s
o
u
n
d
(
<
3
d
a
y
s
)
8
3
.
2
3
8
.
6
2
1
.
4
9
1
.
5
3
3
.
8
Y
e
s
r
e
t
r
o
s
p
e
c
t
i
v
e
-
2
0
0
9
f
e
v
e
r
(
>
3
8

C
)
H
i
g
h
-
g
r
a
d
e
:
1
7
.
0
%
6
.
L
e
e
e
t
a
l
.
[
1
4
]
2
2
0
(
<
2
Y
/
O
)
i
n
6
.
5
Y
A
l
l
g
r
a
d
e
:
3
0
.
4
%
D
M
S
A
s
c
a
n
(
?
)
a
n
d
r
e
n
a
l
u
l
t
r
a
s
o
u
n
d
(
i
m
m
e
d
i
a
t
e
l
y
)
9
5
.
3
Y
e
s
r
e
t
r
o
s
p
e
c
t
i
v
e
-
2
0
0
9
F
e
v
e
r
(
>
3
8
.
5

C
)
H
i
g
h
-
g
r
a
d
e
:
1
9
.
5
%
7
.
F
o
u
z
a
s
e
t
a
l
.
[
1
5
]
2
9
6
(
<
2
Y
/
O
)
i
n
5
Y
,
m
e
d
i
a
n
a
g
e
5
M
A
l
l
g
r
a
d
e
:
2
0
.
9
%
D
M
S
A
s
c
a
n
(
7
-
1
4
d
a
y
s
a
f
t
e
r
d
i
a
g
n
o
s
i
s
)
a
n
d
r
e
n
a
l
u
l
t
r
a
s
o
u
n
d
(
<
7
d
a
y
s
)
7
3
.
9
5
6
.
0
2
3
.
6
9
2
.
1
5
1
.
3
N
o
p
r
o
s
p
e
c
t
i
v
e
-
2
0
1
0
f
e
v
e
r
(
>
3
8

C
)
H
i
g
h
-
g
r
a
d
e
:
1
5
.
5
%
(
L
o
w
s
e
n
s
i
t
i
v
i
t
y
)
8
.
Q
u
i
r
i
n
o
e
t
a
l
.
[
1
6
]
5
3
3
(
<
3
Y
/
O
)
i
n
2
3
Y
A
l
l
g
r
a
d
e
4
6
.
2
%
D
M
S
A
s
c
a
n
(
>
3
m
o
n
t
h
s
)
a
n
d
r
e
n
a
l
u
l
t
r
a
s
o
u
n
d
(
d
u
r
i
n
g
h
o
s
p
i
t
a
l
i
z
a
t
i
o
n
)
9
7
.
0
9
7
.
0
3
7
.
0
Y
e
s
r
e
t
r
o
s
p
e
c
t
i
v
e
-
2
0
1
1
f
e
v
e
r
(
d
e
f
i
n
i
t
i
o
n
?
)
H
i
g
h
-
g
r
a
d
e
:
2
7
.
0
%
9
.
T
s
a
i
e
t
a
l
.
2
2
0
(
<
3
M
/
O
)
i
n
3
.
5
Y
A
l
l
g
r
a
d
e
:
2
7
.
3
%
D
M
S
A
s
c
a
n
(
<
5
d
a
y
s
a
f
t
e
r
a
d
m
i
s
s
i
o
n
)
a
n
d
u
l
t
r
a
s
o
u
n
d
(
<
3
d
a
y
s
a
f
t
e
r
a
d
m
i
s
s
s
i
o
n
)
9
2
.
3
2
7
.
6
2
1
.
6
9
4
.
3
2
4
.
1
Y
e
s
p
r
o
s
p
e
c
t
i
v
e
(
t
h
i
s
r
e
p
o
r
t
)
f
e
v
e
r
(
3
8

C
)
H
i
g
h
-
g
r
a
d
e
:
1
7
.
7
%
Pediatr Nephrol (2012) 27:955963 961
screening tool for detecting high-grade VUR. If VCUG is
performed only in children with abnormal results on renal
US, DMSA, or both, 53 (24.1%) fewer VCUGs will be
performed. According to the study reported by Pohl, con-
sidering a charge of US $852 per VCUG, the cost saving
with this approach would be US $45,156 [31]. In this study,
we only assess the value of acute DMSA and US in reveal-
ing high-grade VUR but do not provide information about
long-term renal consequence. Because the benefit of identi-
fying high-grade VUR is still in doubt, [7], this screening
strategy is useful only when intervention of high-grade
VUR can be proved to change a patients future risk or
long-term outcome.
The limitations of our study are that the quality of per-
formance of prenatal US is not assured, and the information
of voiding dysfunction is not evaluated. The use of DMSA
scan is criticized for higher costs, longer duration, radiation
exposure, and requirement of special equipment [26]. As
pointed out by Flynn, it is difficult, even in developed
countries, to schedule a every young child with febrile
UTI for both US and DMSA scan during the acute episode
[32]. The OR rule strategy also carries the disadvantage of
missing infants with low-grade VUR. Although most
experts agree that low-grade VUR is of low clinical signif-
icance, antibiotic prophylaxis is still recommended by AUA
guidelines for infants<1 year of age with VUR and a history
of a febrile UTI in the new [6].
In conclusion, ultrasound and DMSA scan have different
but complementary roles in evaluating kidneys and urinary
tract. Whereas they cannot adequately predict high-grade
VUR, they each contribute something to the assessment.
The OR rule strategy has the highest sensitivity and NPV
for screening high-grade VUR.
Conflict of interest None of the authors have any conflict of interest
related to the investigation.
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