# Diagnostic Approach to Reflux in 2007

Authors: Sumit Dave; Antoine E. Khoury
Journal: Advances in Urology
 (2008)

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## Abstract

There is ongoing controversy regarding the association between vesicoureteric reflux (VUR), recurrent urinary tract infections (UTI), and renal damage. Despite this, routine work up for VUR is still recommended after febrile UTI in most children. The present article reviews the indications and imaging modalities available for VUR diagnosis. Alternative newer techniques like MR cystography and voiding urosonography are discussed. The increasing evidence of the role of DMSA scans in managing children with VUR is highlighted.


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## Body

## 1. Introduction

The goals of an imaging  procedure
in general are to confirm the diagnosis suspected with a high degree of
sensitivity and specificity, to aid treatment  and allow prognostication. On the
other hand, it is obligatory for the treating physician to analyze the risks
and benefits of the diagnostic procedure and understand the natural history of
the disease in question to establish whether or not the diagnosis and treatment
of a condition would alter long term outcome or impact management decisions.The diagnosis of vesicoureteric
reflux (VUR) is a relatively straightforward and well-established procedure.
However, the underlying rationale for identifying VUR to prevent recurrent
pyelonephritis (PN) and long-term renal damage has been vigorously questioned
in the recent literature [1–4]. Coupled with this, there has been the
increasing awareness of the risks of radiation exposure and the realization
that VUR investigation is an invasive procedure and definitely an unpleasant
experience. Therefore, it is imperative for the pediatric urologist and
nephrologist to reevaluate the indications and goals for imaging for VUR,
redefine the modalities used, and establish guidelines for followup.The current article reviews the
available modalities for evaluating VUR, suggests protocols for investigating
children with suspected VUR, and presents the recent evidence justifying these
recommendations.


## 2. Imaging Modalities for Diagnosis of VUR

### 2.1. Voiding Cystourethrogram (VCUG) or  Radionuclide Cystogram (RNC)

An ideal test for VUR detection
would be one involving no radiation, no bladder catheterization, no sedation,
low cost, high sensitivity, and one which provides complete anatomical details.
The traditional method for diagnosing VUR is the fluoroscopic voiding cystourethrogram
(VCUG). Currently, radionuclide cystography (RNC) remains the primary
alternative to a VCUG in evaluating VUR. The objection to performing a VCUG is
related to the high radiation exposure of a traditional VCUG which is believed
to be about 100 times that of a RNC. However, with the judicious use of digital
and pulsed fluoroscopy with meticulous image coning, the radiation exposure
from a VCUG has been significantly reduced [5]. Despite these measures, the
average ovarian radiation dose was shown to be about 10 times greater in a VCUG
when compared with an RNC [6]. The proponents of RNC argue that this
effectively reduces the sensitivity of the VCUG in identifying VUR as snapshots
of the bladder filling and voiding are taken rather than continuous imaging. In
an editorial comment, Benson stated that “the radiation dose given during 3
minutes of fluoroscopy time approximates that of two pelvic spiral CT scans
with contrast, 1.5 conventional abdominal CT scans without contrast, 3 DMSA
scans, 60 abdominal plain films, 600 radionuclide VCUG’s, or 10 years of
background radiation” [7].Several studies have compared the
sensitivity of VCUG and RNC and  concluded that RNC is at least as sensitive as
or more than a VCUG for detecting VUR [8–10]. Sükan et al. observed no
significant difference between the 2 modalities but noted that RNC offered a
higher sensitivity in the younger age group [8]. Moreover, despite not reaching
statistical significance, in children with a positive dimercapto-succinic acid
(DMSA) scan, RNC identified VUR in a higher percentage of children as opposed
to the VCUG. This is a relevant finding in the current era where a positive
DMSA scan is believed to be an important finding in children presenting with PN
(as discussed later). An insignificant grade 1 VUR may be missed on an RNC but
the continuous imaging during filling and voiding allows greater detection of
VUR, which is an intermittent phenomenon.
For both tests, it is well established that a cyclic study should be
performed to increase the detection of VUR [11]. The definite advantage a VCUG
has over an RNC lies in the anatomical information obtained by the former
especially in evaluating the urethra in males. Moreover, the International
Reflux grading system is based on the VCUG and since most studies on VUR have
used this grading system, treating physicians feel more comfortable in knowing
this information. However, again as a result of change in treatment philosophy,
it can be argued that a broader classification of VUR into dilating (≥Grade 3)
and nondilating varieties is possible on an RNC, making this an insignificant
issue when deciding on the study to obtain. Therefore, currently VCUG remains
the standard when initially evaluating a child with suspected VUR. For all subsequent
studies, the RNC is the preferred modality. Medina et al. performed a cost
analysis of VUR imaging using VCUG and RNC, highlighting another potential
reason for preferring the RNC for followup imaging [12]. The study showed that
the direct costs of performing a VCUG was 1.74 times higher than an RNC (P<.001).


### 2.2. Indirect RNC

The indirect RNC offers the
possibility of detecting VUR without bladder catheterization and presumably in
a more physiological setting with natural bladder filling. The additional
advantage is the ability to assess upper tract differential function and
drainage with the injected radioisotope. Although a few reports have shown a
comparable degree of sensitivity between the direct and indirect RNC, the
consensus is that due to an inability to study the filling phase with an
indirect RNC there is a considerable false negative rate with indirect RNC
[13–15]. There may be a role of the indirect RNC as a followup study in
children who are toilet trained [14].


### 2.3. Voiding Urosonography (VUS)

The sonographic evaluation of VUR
following intravesical instillation of US
contrast agent has gradually
popularized VUS over the last decade. In a comprehensive review of VUS when
compared with VCUG, Darge showed that in 1338 patients with 2893 refluxing
units, VUS showed a diagnostic accuracy of 78%–96% [16]. The overall
agreement between the 2 studies was 91% and in 9% of renal units VUR was
detected only on VUS making it the more sensitive study. Another potential
advantage of the VUS as compared to RNC is the ability to grade VUR similar to
the International Reflux grading system with a 75% concordance shown between
the VUS and VCUG grading. The discordant findings are primarily because of a
significant number of grade-1 VUR on VCUG being grade 2 or higher on VUS. The
absence of radiation, the ability to evaluate the upper tracts simultaneously
and its higher sensitivity make it an attractive tool for evaluating VUR. The
potential drawbacks include inadequate evaluation of bladder and urethral morphology,
higher costs of contrast agent, longer exam time, and its operator dependence.
Transperineal US
of the urethra as part of the VUS has been used reliably in a few studies to
date but further evaluation of this technique is necessary before VUS can replace
the VCUG as the first examination for VUR especially in boys [17]. At present,
VUS has a role in followup examinations for VUR, for screening siblings and
possibly as the first examination for VUR in girls.


### 2.4. MR Voiding Cystography (MRVCUG)

MR cystography involves intravesical administration of
gadolinium with imaging using MR during filling and voiding. The relative
benefits of the procedure are that it can evaluate VUR without ionizing
radiation and additionally give important information about renal-acquired
cortical defects and differentiate acquired cortical defects from congenital
dysplasia. It must be borne in mind that dysplasia and scarring are different
entities diagnosed on histopathological examination. In this paper we refer to
them as congenital and acquired cortical defects. The potential drawbacks
include a lower sensitivity as compared to VCUG, higher costs, and the need for
sedation or anesthesia to perform the study. Takazakura et al. showed 90%
sensitivity and a 96% specificity of MRVCUG and all children with grade 3 or
more VUR were identified using this modality [18]. Lee et al. further
correlated the MRVCUG findings with a DMSA SPECT scan to demonstrate the
advantage of getting this additional information with a single test [19].


### 2.5. PIC Cystogram

Rubenstein et al. in 2003
introduced a novel but controversial technique to identify VUR in children
presenting with febrile UTIs and negative VCUG [20]. The authors performed the
PIC (Positioning the Instillation of Contrast at the ureteral orifice)
cystogram by positioning the cystoscope close to the ureteric orifice with the
bladder empty and instilling contrast in gravity-aided manner from a height of
1 m using the irrigation port of the scope. The argument that this technique
could induce VUR was countered by using a control group of children without UTI
and VUR where the PIC cystogram also did not demonstrate reflux. In contrast,
all children with febrile UTIs and no VUR on VCUG showed VUR on the PIC
cystogram. A multi-institutional study confirmed that PIC VUR could be
demonstrated in 82% of children who present with febrile UTI and normal VCUG
[21]. The inherent problem with both these studies has been the lack of
standardization of the VCUG technique used, absence of upper tract imaging
findings, and strict definition of UTI. This latter objection has been
addressed in a more recent study by Tareen et al. who evaluated 5 children with
recurrent febrile UTI and upper tract changes on DMSA/CT scan [7]. All 5
patients showed VUR on PIC cystography and went on to endoscopic or open VUR
correction. The results of these studies indicate that the majority of children
with febrile UTI and no VUR on a VCUG would have VUR on a PIC cystogram. Before
adding this investigation as a routine modality for children with febrile UTI
and negative VCUGs, further prospective randomized studies are indicated to
define the population who would benefit from this intervention.


## 2.1. Voiding Cystourethrogram (VCUG) or  Radionuclide Cystogram (RNC)

An ideal test for VUR detection
would be one involving no radiation, no bladder catheterization, no sedation,
low cost, high sensitivity, and one which provides complete anatomical details.
The traditional method for diagnosing VUR is the fluoroscopic voiding cystourethrogram
(VCUG). Currently, radionuclide cystography (RNC) remains the primary
alternative to a VCUG in evaluating VUR. The objection to performing a VCUG is
related to the high radiation exposure of a traditional VCUG which is believed
to be about 100 times that of a RNC. However, with the judicious use of digital
and pulsed fluoroscopy with meticulous image coning, the radiation exposure
from a VCUG has been significantly reduced [5]. Despite these measures, the
average ovarian radiation dose was shown to be about 10 times greater in a VCUG
when compared with an RNC [6]. The proponents of RNC argue that this
effectively reduces the sensitivity of the VCUG in identifying VUR as snapshots
of the bladder filling and voiding are taken rather than continuous imaging. In
an editorial comment, Benson stated that “the radiation dose given during 3
minutes of fluoroscopy time approximates that of two pelvic spiral CT scans
with contrast, 1.5 conventional abdominal CT scans without contrast, 3 DMSA
scans, 60 abdominal plain films, 600 radionuclide VCUG’s, or 10 years of
background radiation” [7].Several studies have compared the
sensitivity of VCUG and RNC and  concluded that RNC is at least as sensitive as
or more than a VCUG for detecting VUR [8–10]. Sükan et al. observed no
significant difference between the 2 modalities but noted that RNC offered a
higher sensitivity in the younger age group [8]. Moreover, despite not reaching
statistical significance, in children with a positive dimercapto-succinic acid
(DMSA) scan, RNC identified VUR in a higher percentage of children as opposed
to the VCUG. This is a relevant finding in the current era where a positive
DMSA scan is believed to be an important finding in children presenting with PN
(as discussed later). An insignificant grade 1 VUR may be missed on an RNC but
the continuous imaging during filling and voiding allows greater detection of
VUR, which is an intermittent phenomenon.
For both tests, it is well established that a cyclic study should be
performed to increase the detection of VUR [11]. The definite advantage a VCUG
has over an RNC lies in the anatomical information obtained by the former
especially in evaluating the urethra in males. Moreover, the International
Reflux grading system is based on the VCUG and since most studies on VUR have
used this grading system, treating physicians feel more comfortable in knowing
this information. However, again as a result of change in treatment philosophy,
it can be argued that a broader classification of VUR into dilating (≥Grade 3)
and nondilating varieties is possible on an RNC, making this an insignificant
issue when deciding on the study to obtain. Therefore, currently VCUG remains
the standard when initially evaluating a child with suspected VUR. For all subsequent
studies, the RNC is the preferred modality. Medina et al. performed a cost
analysis of VUR imaging using VCUG and RNC, highlighting another potential
reason for preferring the RNC for followup imaging [12]. The study showed that
the direct costs of performing a VCUG was 1.74 times higher than an RNC (P<.001).


## 2.2. Indirect RNC

The indirect RNC offers the
possibility of detecting VUR without bladder catheterization and presumably in
a more physiological setting with natural bladder filling. The additional
advantage is the ability to assess upper tract differential function and
drainage with the injected radioisotope. Although a few reports have shown a
comparable degree of sensitivity between the direct and indirect RNC, the
consensus is that due to an inability to study the filling phase with an
indirect RNC there is a considerable false negative rate with indirect RNC
[13–15]. There may be a role of the indirect RNC as a followup study in
children who are toilet trained [14].


## 2.3. Voiding Urosonography (VUS)

The sonographic evaluation of VUR
following intravesical instillation of US
contrast agent has gradually
popularized VUS over the last decade. In a comprehensive review of VUS when
compared with VCUG, Darge showed that in 1338 patients with 2893 refluxing
units, VUS showed a diagnostic accuracy of 78%–96% [16]. The overall
agreement between the 2 studies was 91% and in 9% of renal units VUR was
detected only on VUS making it the more sensitive study. Another potential
advantage of the VUS as compared to RNC is the ability to grade VUR similar to
the International Reflux grading system with a 75% concordance shown between
the VUS and VCUG grading. The discordant findings are primarily because of a
significant number of grade-1 VUR on VCUG being grade 2 or higher on VUS. The
absence of radiation, the ability to evaluate the upper tracts simultaneously
and its higher sensitivity make it an attractive tool for evaluating VUR. The
potential drawbacks include inadequate evaluation of bladder and urethral morphology,
higher costs of contrast agent, longer exam time, and its operator dependence.
Transperineal US
of the urethra as part of the VUS has been used reliably in a few studies to
date but further evaluation of this technique is necessary before VUS can replace
the VCUG as the first examination for VUR especially in boys [17]. At present,
VUS has a role in followup examinations for VUR, for screening siblings and
possibly as the first examination for VUR in girls.


## 2.4. MR Voiding Cystography (MRVCUG)

MR cystography involves intravesical administration of
gadolinium with imaging using MR during filling and voiding. The relative
benefits of the procedure are that it can evaluate VUR without ionizing
radiation and additionally give important information about renal-acquired
cortical defects and differentiate acquired cortical defects from congenital
dysplasia. It must be borne in mind that dysplasia and scarring are different
entities diagnosed on histopathological examination. In this paper we refer to
them as congenital and acquired cortical defects. The potential drawbacks
include a lower sensitivity as compared to VCUG, higher costs, and the need for
sedation or anesthesia to perform the study. Takazakura et al. showed 90%
sensitivity and a 96% specificity of MRVCUG and all children with grade 3 or
more VUR were identified using this modality [18]. Lee et al. further
correlated the MRVCUG findings with a DMSA SPECT scan to demonstrate the
advantage of getting this additional information with a single test [19].


## 2.5. PIC Cystogram

Rubenstein et al. in 2003
introduced a novel but controversial technique to identify VUR in children
presenting with febrile UTIs and negative VCUG [20]. The authors performed the
PIC (Positioning the Instillation of Contrast at the ureteral orifice)
cystogram by positioning the cystoscope close to the ureteric orifice with the
bladder empty and instilling contrast in gravity-aided manner from a height of
1 m using the irrigation port of the scope. The argument that this technique
could induce VUR was countered by using a control group of children without UTI
and VUR where the PIC cystogram also did not demonstrate reflux. In contrast,
all children with febrile UTIs and no VUR on VCUG showed VUR on the PIC
cystogram. A multi-institutional study confirmed that PIC VUR could be
demonstrated in 82% of children who present with febrile UTI and normal VCUG
[21]. The inherent problem with both these studies has been the lack of
standardization of the VCUG technique used, absence of upper tract imaging
findings, and strict definition of UTI. This latter objection has been
addressed in a more recent study by Tareen et al. who evaluated 5 children with
recurrent febrile UTI and upper tract changes on DMSA/CT scan [7]. All 5
patients showed VUR on PIC cystography and went on to endoscopic or open VUR
correction. The results of these studies indicate that the majority of children
with febrile UTI and no VUR on a VCUG would have VUR on a PIC cystogram. Before
adding this investigation as a routine modality for children with febrile UTI
and negative VCUGs, further prospective randomized studies are indicated to
define the population who would benefit from this intervention.


## 3. Indications for Imaging for Suspected VUR

The primary indications for
evaluating children for VUR are discussed in this section. There has been
considerable evolution of our knowledge about VUR management over the last
several years. The role of antibiotic prophylaxis in preventing recurrent
infections has been challenged along with an increasing awareness of the
development of antibiotic resistance [1–3]. This coupled with identification of
other stronger predicting factors for recurrent infection like lower urinary
tract dysfunction (LUTS) has led to a more conservative approach in identifying
and treating VUR [22]. This section suggests recommendations for the evaluation
of children with suspected VUR.


### 3.1. Children with Urinary Tract  Infection

The American Academy of Pediatrics: Committee on Quality Improvement recommends a VCUG for all children
aged between 2 months to 2 years old following the first febrile UTI [23].  The rationale for this practice is based on
the traditional view that there is always uncertainty about whether previous
infections were missed, high recurrence rates of UTI, high percentage of
children with UTI having VUR and that the risk of renal-acquired cortical
defects is highest in younger children. In practice, however, this
recommendation is often not followed rigidly primarily because of poor
documentation of significant bacteriuria and pyuria which puts in doubt the
diagnosis of a UTI. For older children, age at presentation, gender, race, type
(febrile or non febrile), frequency of UTI, and social factors must be
considered before proceeding to a VCUG. Toilet-trained female children with
cystitis are primarily evaluated by a full voiding diary and the dysfunctional
voiding symptom score (DVSS) rather than a VCUG [24]. In children with
recurrent cystitis a uroflowmetry and US are added. However, in the presence of
a well-documented episode of PN or recurrent febrile UTI, a VCUG or RNC is
warranted along with a US or DMSA scan to assess the upper tracts. All males with a well-documented
febrile UTI should undergo a VCUG. Because of the well-documented low incidence
of VUR in black children, a VCUG is not indicated for older black children
presenting with UTI. The initial VCUG can be performed after the child is
afebrile, clinically stable and the urine is sterile [25]. The dose of
antibiotic prophylaxis is doubled a day before the test and continued at
therapeutic levels for another day following the test.


### 3.2. Sibling VUR

Primary VUR is the commonest
heritable disorder of the genitourinary tract and is inherited as a Mendelian
dominant with partial expression [26]. Several studies on sibling VUR have
identified factors, which can help predict the risk of sibling VUR. Hollowell in an analysis of 1768 siblings showed a mean VUR incidence of 32%,
which was 44% in siblings less than 2 years of age as compared to 9% of
siblings greater than 6 years [27]. If the sex of the sibling or proband is
considered separately there is no statistical association. On the other hand,
female siblings of the female index patient have a higher likelihood of VUR
than their male counterparts [28]. Monozygotic twins have an obviously higher
risk than dizygotic twins. Hollowell showed that approximately two-thirds of
siblings have low grade (I, II) VUR and the spontaneous resolution rate is
higher when compared to children diagnosed with VUR after a UTI [27]. Giel et
al. presented the long-term outcome of asymptomatic siblings screened for VUR
with an initial US [29]. Of the 117 siblings in this study, 11 (9.4%) had
abnormal US
findings, 5 of which showed VUR on a VCUG. In 85 siblings with an average
followup of more than 8 years, none had complications of VUR. Other authors
have argued for a more proactive approach in diagnosing VUR in siblings
[30, 31]. Houle et al. demonstrated a 26% incidence of cortical defects in
siblings and indicated that siblings screened after 2 years of age had a higher
risk of renal damage [30]. The alternative argument here is that perhaps these
findings represent congenital defects rather than acquired preventable defects.A tailored approach for siblings
therefore could be an RNC or a VUS in siblings younger than the toilet-trained
age and US as the initial screening modality for all older siblings. In the
presence of any US evidence of cortical damage a VCUG is recommended in children under 5 years of
age as they form the subset most at risk of renal damage. Symptomatic siblings
at any age are evaluated with a VCUG.


### 3.3. Prenatal Hydronephrosis and VUR

VUR is suspected antenatally in the
presence of ureteric dilatation and/or hydronephrosis (HN) or following the diagnosis
of ectopic kidneys, multicystic dysplastic kidney, and unilateral renal
agenesis wherein there is an increased incidence of contra lateral VUR. Van
Eerde et al. performed a meta-analysis to review the value of antenatal HN in
predicting postnatal VUR [32]. HN was defined as renal pelvic diameter more
than 4 mm with or without caliectasis. Among the 1178 cases, the mean prevalence
of primary VUR was 14.9%. When stratified by anteroposterior renal pelvic
diameter (APD), VUR was diagnosed in 14% of infants with APD≤10mm and in 12% of infants with APD≥10mm. It is known that a negative prenatal screening
or a normal postnatal US in infants with antenatal HN does not rule out VUR. In a meta-analysis reported by Lee et al., the prevalence of VUR ranged between 4.4% and 14% [33]. There was no
correlation between the degree of prenatal HN and the presence or grade of VUR.
Similarly, in another study conducted on 108 children with antenatal HN, VUR
was detected in 15% and there was no correlation between the degree of
pelviectasis on postnatal US and the presence or severity of VUR [34]. Children
with antenatal HN and VUR have a more benign course with a higher resolution
rate when compared to children diagnosed with VUR following a UTI [35, 36].
Upadhyay et al. followed 25 children with antenatally detected HN and VUR [36].
Reflux was greater than or equal to grade III in 70% of children. VUR resolved
in 52% and was downgraded in 24%. Breakthrough urinary tract infection
occurred in 4 patients with grades IV and V reflux, and dysfunctional voiding
developed in 5. Followup renal scans showed decreased differential function
(mean 18%) in 2 units without new scars. A selective approach is advisable for
investigating neonates with antenatal HN.  If the renal size and parenchyma is
unremarkable, it may be reasonable to reserve the VCUG for children with SFU
grade 3-4 HN or bilateral HN and in the presence of ureteric dilatation.


### 3.4. Other Situations

A routine VCUG is recommended in
the work up of children with multicystic dysplastic kidneys (MCDK) based on the
reported 15%–25% prevalence of VUR in children with MCDK [37–40]. Miller et al. found a 25% VUR rate in the contralateral kidney in 75 patients with MCDK [37].
In this series, about 50% of  children with VUR had grades ≥3, 50% resolved
spontaneously by 5 years of age and only 1 of the 75 children required surgical
intervention for VUR. Guarino et al. documented that 16% of children with MCDK
had VUR and the VUR grade was significantly higher in boys as compared to girls
[39]. This finding was also noted in the study by Selzman and Elder, wherein 15% of children showed contralateral VUR, with the prevalence being higher in
boys and the white population [40]. Ismaili et al. recommended that 2
successive normal US
studies in the neonatal period identifie most significant contralateral
anomalies avoiding the use of a routine VCUG [38]. In their study, 61 of the 76
newborns with MCDK had 2 normal neonatal US. Among them, 4 (7%) had low grade
VUR which resolved spontaneously in all before 2 years of age. Further studies
are needed to validate this finding before stopping routine VCUGs in children
with MCDK.The incidence of VUR in children
with unilateral renal agenesis (URA) is slightly higher than MCDK and varies
between 24%–28% [39, 41–43]. The VUR
can be high grade and shows a lower spontaneous resolution rate as compared to
MCDK [41]. Arena et al. evaluated 60 children with renal ectopia (crossed 24,
simple 36) [44].  The authors recommended
complete urological evaluation of children presenting with renal ectopia. The
incidence of associated VUR was 37% with crossed ectopia and 17% with simple
ectopia.  Unlike MCDK, Guarino et al.
noted that girls had a higher grade of VUR and lower resolution rates [39]. In
view of the high incidence of neurogenic bladder dysfunction and VUR (20%–47%)
children with anorectal malformation should also undergo a VCUG [45].


## 3.1. Children with Urinary Tract  Infection

The American Academy of Pediatrics: Committee on Quality Improvement recommends a VCUG for all children
aged between 2 months to 2 years old following the first febrile UTI [23].  The rationale for this practice is based on
the traditional view that there is always uncertainty about whether previous
infections were missed, high recurrence rates of UTI, high percentage of
children with UTI having VUR and that the risk of renal-acquired cortical
defects is highest in younger children. In practice, however, this
recommendation is often not followed rigidly primarily because of poor
documentation of significant bacteriuria and pyuria which puts in doubt the
diagnosis of a UTI. For older children, age at presentation, gender, race, type
(febrile or non febrile), frequency of UTI, and social factors must be
considered before proceeding to a VCUG. Toilet-trained female children with
cystitis are primarily evaluated by a full voiding diary and the dysfunctional
voiding symptom score (DVSS) rather than a VCUG [24]. In children with
recurrent cystitis a uroflowmetry and US are added. However, in the presence of
a well-documented episode of PN or recurrent febrile UTI, a VCUG or RNC is
warranted along with a US or DMSA scan to assess the upper tracts. All males with a well-documented
febrile UTI should undergo a VCUG. Because of the well-documented low incidence
of VUR in black children, a VCUG is not indicated for older black children
presenting with UTI. The initial VCUG can be performed after the child is
afebrile, clinically stable and the urine is sterile [25]. The dose of
antibiotic prophylaxis is doubled a day before the test and continued at
therapeutic levels for another day following the test.


## 3.2. Sibling VUR

Primary VUR is the commonest
heritable disorder of the genitourinary tract and is inherited as a Mendelian
dominant with partial expression [26]. Several studies on sibling VUR have
identified factors, which can help predict the risk of sibling VUR. Hollowell in an analysis of 1768 siblings showed a mean VUR incidence of 32%,
which was 44% in siblings less than 2 years of age as compared to 9% of
siblings greater than 6 years [27]. If the sex of the sibling or proband is
considered separately there is no statistical association. On the other hand,
female siblings of the female index patient have a higher likelihood of VUR
than their male counterparts [28]. Monozygotic twins have an obviously higher
risk than dizygotic twins. Hollowell showed that approximately two-thirds of
siblings have low grade (I, II) VUR and the spontaneous resolution rate is
higher when compared to children diagnosed with VUR after a UTI [27]. Giel et
al. presented the long-term outcome of asymptomatic siblings screened for VUR
with an initial US [29]. Of the 117 siblings in this study, 11 (9.4%) had
abnormal US
findings, 5 of which showed VUR on a VCUG. In 85 siblings with an average
followup of more than 8 years, none had complications of VUR. Other authors
have argued for a more proactive approach in diagnosing VUR in siblings
[30, 31]. Houle et al. demonstrated a 26% incidence of cortical defects in
siblings and indicated that siblings screened after 2 years of age had a higher
risk of renal damage [30]. The alternative argument here is that perhaps these
findings represent congenital defects rather than acquired preventable defects.A tailored approach for siblings
therefore could be an RNC or a VUS in siblings younger than the toilet-trained
age and US as the initial screening modality for all older siblings. In the
presence of any US evidence of cortical damage a VCUG is recommended in children under 5 years of
age as they form the subset most at risk of renal damage. Symptomatic siblings
at any age are evaluated with a VCUG.


## 3.3. Prenatal Hydronephrosis and VUR

VUR is suspected antenatally in the
presence of ureteric dilatation and/or hydronephrosis (HN) or following the diagnosis
of ectopic kidneys, multicystic dysplastic kidney, and unilateral renal
agenesis wherein there is an increased incidence of contra lateral VUR. Van
Eerde et al. performed a meta-analysis to review the value of antenatal HN in
predicting postnatal VUR [32]. HN was defined as renal pelvic diameter more
than 4 mm with or without caliectasis. Among the 1178 cases, the mean prevalence
of primary VUR was 14.9%. When stratified by anteroposterior renal pelvic
diameter (APD), VUR was diagnosed in 14% of infants with APD≤10mm and in 12% of infants with APD≥10mm. It is known that a negative prenatal screening
or a normal postnatal US in infants with antenatal HN does not rule out VUR. In a meta-analysis reported by Lee et al., the prevalence of VUR ranged between 4.4% and 14% [33]. There was no
correlation between the degree of prenatal HN and the presence or grade of VUR.
Similarly, in another study conducted on 108 children with antenatal HN, VUR
was detected in 15% and there was no correlation between the degree of
pelviectasis on postnatal US and the presence or severity of VUR [34]. Children
with antenatal HN and VUR have a more benign course with a higher resolution
rate when compared to children diagnosed with VUR following a UTI [35, 36].
Upadhyay et al. followed 25 children with antenatally detected HN and VUR [36].
Reflux was greater than or equal to grade III in 70% of children. VUR resolved
in 52% and was downgraded in 24%. Breakthrough urinary tract infection
occurred in 4 patients with grades IV and V reflux, and dysfunctional voiding
developed in 5. Followup renal scans showed decreased differential function
(mean 18%) in 2 units without new scars. A selective approach is advisable for
investigating neonates with antenatal HN.  If the renal size and parenchyma is
unremarkable, it may be reasonable to reserve the VCUG for children with SFU
grade 3-4 HN or bilateral HN and in the presence of ureteric dilatation.


## 3.4. Other Situations

A routine VCUG is recommended in
the work up of children with multicystic dysplastic kidneys (MCDK) based on the
reported 15%–25% prevalence of VUR in children with MCDK [37–40]. Miller et al. found a 25% VUR rate in the contralateral kidney in 75 patients with MCDK [37].
In this series, about 50% of  children with VUR had grades ≥3, 50% resolved
spontaneously by 5 years of age and only 1 of the 75 children required surgical
intervention for VUR. Guarino et al. documented that 16% of children with MCDK
had VUR and the VUR grade was significantly higher in boys as compared to girls
[39]. This finding was also noted in the study by Selzman and Elder, wherein 15% of children showed contralateral VUR, with the prevalence being higher in
boys and the white population [40]. Ismaili et al. recommended that 2
successive normal US
studies in the neonatal period identifie most significant contralateral
anomalies avoiding the use of a routine VCUG [38]. In their study, 61 of the 76
newborns with MCDK had 2 normal neonatal US. Among them, 4 (7%) had low grade
VUR which resolved spontaneously in all before 2 years of age. Further studies
are needed to validate this finding before stopping routine VCUGs in children
with MCDK.The incidence of VUR in children
with unilateral renal agenesis (URA) is slightly higher than MCDK and varies
between 24%–28% [39, 41–43]. The VUR
can be high grade and shows a lower spontaneous resolution rate as compared to
MCDK [41]. Arena et al. evaluated 60 children with renal ectopia (crossed 24,
simple 36) [44].  The authors recommended
complete urological evaluation of children presenting with renal ectopia. The
incidence of associated VUR was 37% with crossed ectopia and 17% with simple
ectopia.  Unlike MCDK, Guarino et al.
noted that girls had a higher grade of VUR and lower resolution rates [39]. In
view of the high incidence of neurogenic bladder dysfunction and VUR (20%–47%)
children with anorectal malformation should also undergo a VCUG [45].


## 4. What Should the First Investigation Following Pyelonephritis Be: DMSA or VCUG?

Primary VUR occurs in less than 1%
of the general population but up to 50% of children who present with a UTI
will have VUR [46]. Therefore, the detection of VUR is an abnormal
finding.  The primary reason for
identifying VUR as a disease entity has been its association with pyelonephritis
(PN), which, if recurrent, can lead to acquired cortical defects and subsequent
hypertension and/or end stage renal failure. This perception that the triad of
UTI-VUR-nephropathy is an intimate link has driven physicians to actively
diagnose and treat VUR over the last 3 decades.There is a considerable debate
regarding the initial investigation following a febrile UTI with several
studies highlighting the emerging role of DMSA scan vis a vis the VCUG. The
rationale for this argument stems from the recent evidence which has downgraded
the importance of VUR as a sole factor in causing long-term renal damage. In
fact, our aggressive management of VUR over the last several decades has not
impacted long-term renal outcome. Craig et al. reviewed the Australia
and New Zealand Dialysis
and Transplant Registry between 1971 and 1998 and noted that over the decades,
despite a more aggressive identification and treatment of VUR, reflux
nephropathy continued to remain a cause of ESRD in about 14% of children
registered [47]. This section discusses this current thought process and
refocuses our attention to our primary goal which is the identification of risk
factors which lead to progressive renal damage.


### 4.1. Pyelonephritis and Acquired Cortical  Defects can Occur without VUR

Recent studies have demonstrated
that acquired renal scarring correlates best with recurrent UTI and not with
VUR and primary VUR is neither sufficient nor essential for renal damage. The
exception to this rule is secondary reflux associated with bladder outlet
obstruction or high-pressure neurogenic bladders. Gordon et al. performed a
meta-analysis to determine the value of VUR diagnosis to predict renal damage
in children hospitalized with UTI [4]. The analysis evaluated 12 studies
comprising 537 children with 1032 kidneys and showed that primary VUR was a
poor predictor of renal damage on a DMSA scan in children hospitalized with
UTI. A positive VCUG increased the chance of a positive DMSA scan by only about
20% whereas a negative VCUG increased the chance of negative DMSA scan by 8%.
The authors concluded that the VCUG could not be used as a primary screening
test to detect renal parenchymal damage in children with UTI. Taskinen and
Rönnholm noted that fever more than 39°C, CRP>100mg/mL, and proteinuria
during UTI were predictors of renal damage [48]. The presence of VUR did not
increase the risk of renal defects on DMSA scanning. On followup, DMSA scans 2
years following UTI, 9 of the 12 patients who showed evidence of cortical
defects did not have associated VUR.


### 4.2. Cortical Defects in Children with VUR  Predicts Recurrent Infection

Mingin et al. retrospectively
reviewed records of children who underwent DMSA scans following a febrile UTI
or antenatal HN [49]. 88% of the children with an abnormal DMSA scan had grade
3–5 VUR. Of the 51 children with an abnormal DMSA and grade 3–5 VUR 60% had a subsequent
breakthrough UTI. In comparison, only 6% of children with similar VUR grade and
a normal DMSA scan developed breakthrough infection. Furthermore, only 5% of
children with an abnormal DMSA scan showed improvement in VUR grade on followup
as compared to a 46% resolution rate in those without DMSA abnormality, a fact
only partly attributable to the lower initial grade of VUR in this subset.


### 4.3. A positive DMSA Scan Identifies Significant  VUR in Most Instances

In 303 children less than 2 years of age
evaluated with VCUG and DMSA scans after an episode of UTI, Hansson et al.
found that 51% had an abnormal DMSA scan and 46% with a positive DMSA scan
had no evidence of VUR on VCUG [50]. There was a significant association
between ≥grade III VUR and DMSA positive renal lesions. A normal DMSA scan and
dilating VUR were found in only 7 children in this study,  of
which only 1 showed a scarred kidney on followup. None of the 7 children had
recurrent UTI on followup. The authors suggested that DMSA could replace VCUG
as the primary evaluation for children following a UTI. VCUGs could be
selectively performed in children with abnormalities on DMSA scans and this
would reduce the number of VCUGs by about half based on the results of this
study. The same group conducted a further prospective study to test this
hypothesis [51]. In 290 children with UTI in infancy, 52 had VUR which was
dilating in 27.  An abnormal DMSA scan
was documented in 26 of the 27 children with dilating VUR. Tseng et al. also
attempted to answer this question whether a normal DMSA can obviate the need
for a VCUG following the first UTI [52]. In 142 children, only 5 children with
a normal DMSA scan had VUR (all less than or equal to grade 2) and no child
with dilating reflux had a normal DMSA scan. Table 1 summarizes these results.Table 1
Results of studies analyzing concordance between DMSA and VCUG findings.
Study (N)POS DMSA POS VCUGPOS DMSA NEG VCUGNEG DMSA POS VCUGNEG DMSA NEG VCUGHansson et al. (303)53 (17%)103 (34%)27(9%);≥III VUR in 7120 (39%)Tseng et al. (142)37 (26%)64 (45%)5(3.5%);≥III VUR in 036 (25%)Preda et al. (290)44 (15%)105 (36%)8(2.7%);≥III VUR in 1133 (46%)


### 4.4. Antibiotic Prophylaxis Does not Prevent Recurrent UTI in Children with Low-Grade VUR

The role of VUR, especially lower
grades, as a predisposing factor for recurrent UTI is also controversial. Nuutinen and Uhari noted a higher rate of
recurrent UTIs in children with grade III–V VUR in comparison with children
with grade I-II VUR [53]. It is now believed that the susceptibility for
recurrent UTI is more related to a defective urothelial defense mechanism and
bladder dysfunction rather than associated VUR. Roussey-Kessler et al.
conducted a prospective study on children with grade 1–3 VUR randomized to
receive cotrimoxazole or no treatment with UTI on followup as an end point [3].
There was no significant difference in the occurrence of UTI in both groups
except in boys with grade 3 VUR (P=.04). Garin et al. performed a
randomized prospective trial in 218 children with or without VUR who presented
with PN, comparing prophylaxis with no prophylaxis [2]. The study only included
patients with grade I–III VUR. No statistically significant differences were
found among the groups with respect to the rate of recurrent UTI, type of
recurrence, rate of subsequent pyelonephritis, and development of renal
parenchymal scars. The overall rate of recurrent PN in this study was 5.5% and
VUR did not increase the likelihood of PN. The authors concluded that at 1-year followup, grade I–III VUR did not increase the incidence of UTI, PN, or
cortical defects. Conway et al. performed a time-to-event analysis on 611
children who are presented with the first UTI to determine the association between antibiotic
prophylaxis and recurrent UTI and to identify risk factors for resistance [54].
The factors associated with an increased risk of recurrent UTI in this study
were white race, age between 3–5 years, and grade IV-V VUR. Sex and grade I–III
VUR were not associated with the risk of recurrence. Moreover, antibiotic
prophylaxis was not associated with a decreased risk of recurrent UTI in a
multivariable analysis but was a risk factor for antibiotic resistance among
children with recurrent UTI.The problem in interpreting studies
attempting to clarify this aspect is the lack of a standardized definition of a
febrile UTI and the variability in the methodology of obtaining urine samples.
The ongoing randomized intervention for children with vesicoureteric reflux (RIVUR)
study is a multicenter, double blinded, randomized, placebo controlled trial
which aims to answer the ongoing controversy regarding the role of antibiotic
prophylaxis in preventing recurrent febrile/symptomatic UTI in children with
VUR diagnosed after a UTI.In summary:(1)
in children presented with a UTI, up to 50% of children may have evidence of upper tract damage without evidence of VUR on a VCUG;(2)
the rate of spontaneous resolution of VUR is higher in children with low-grade VUR and a normal DMSA scan;(3)
a positive DMSA scan at diagnosis predicts a higher rate of recurrent UTI or breakthrough infections in children with VUR;(4)
VUR identification has not altered the ESRD rate related to reflux nephropathy.
The idea behind
these studies is to encourage a more selective approach in investigating
children who present with a first UTI, contrary to the AAP practice guidelines.
A DMSA would be the initial investigation and all children with an abnormal
DMSA will then proceed to a VCUG. This would identify the majority of children
with dilating/significant VUR who would then benefit from antibiotic
prophylaxis, thus reducing both the number of VCUGs and number of children on
antibiotic prophylaxis. Such a selective approach is justifiable with one
objection being that boys with a potential posterior urethral valve presented
outside the neonatal period may be missed with this approach. However, this may
be unlikely if a US study is simultaneously performed as part of the routine work up.


### 4.5. MR Urography (MRU)

MRU is increasingly being advocated
as a single imaging modality, which can be used to provide information obtained
on a VCUG and DMSA scan. The primary advantage of the MRU is its ability to
distinguish between renal dysplasia (congenital cortical defects) and acquired
scarring (acquired cortical defects) [55]. In addition to morphological
analysis, MRU can provide information about renal perfusion, concentration, and
excretion of contrast media by calculating the renal and calyceal transit
times. The Patlak differential function and the calculated Patlak number per mL
of renal tissue is considered a surrogate for the single nephron GFR and can
therefore serve as an important tool in prognosticating and following children
with renal dysplasia.


## 4.1. Pyelonephritis and Acquired Cortical  Defects can Occur without VUR

Recent studies have demonstrated
that acquired renal scarring correlates best with recurrent UTI and not with
VUR and primary VUR is neither sufficient nor essential for renal damage. The
exception to this rule is secondary reflux associated with bladder outlet
obstruction or high-pressure neurogenic bladders. Gordon et al. performed a
meta-analysis to determine the value of VUR diagnosis to predict renal damage
in children hospitalized with UTI [4]. The analysis evaluated 12 studies
comprising 537 children with 1032 kidneys and showed that primary VUR was a
poor predictor of renal damage on a DMSA scan in children hospitalized with
UTI. A positive VCUG increased the chance of a positive DMSA scan by only about
20% whereas a negative VCUG increased the chance of negative DMSA scan by 8%.
The authors concluded that the VCUG could not be used as a primary screening
test to detect renal parenchymal damage in children with UTI. Taskinen and
Rönnholm noted that fever more than 39°C, CRP>100mg/mL, and proteinuria
during UTI were predictors of renal damage [48]. The presence of VUR did not
increase the risk of renal defects on DMSA scanning. On followup, DMSA scans 2
years following UTI, 9 of the 12 patients who showed evidence of cortical
defects did not have associated VUR.


## 4.2. Cortical Defects in Children with VUR  Predicts Recurrent Infection

Mingin et al. retrospectively
reviewed records of children who underwent DMSA scans following a febrile UTI
or antenatal HN [49]. 88% of the children with an abnormal DMSA scan had grade
3–5 VUR. Of the 51 children with an abnormal DMSA and grade 3–5 VUR 60% had a subsequent
breakthrough UTI. In comparison, only 6% of children with similar VUR grade and
a normal DMSA scan developed breakthrough infection. Furthermore, only 5% of
children with an abnormal DMSA scan showed improvement in VUR grade on followup
as compared to a 46% resolution rate in those without DMSA abnormality, a fact
only partly attributable to the lower initial grade of VUR in this subset.


## 4.3. A positive DMSA Scan Identifies Significant  VUR in Most Instances

In 303 children less than 2 years of age
evaluated with VCUG and DMSA scans after an episode of UTI, Hansson et al.
found that 51% had an abnormal DMSA scan and 46% with a positive DMSA scan
had no evidence of VUR on VCUG [50]. There was a significant association
between ≥grade III VUR and DMSA positive renal lesions. A normal DMSA scan and
dilating VUR were found in only 7 children in this study,  of
which only 1 showed a scarred kidney on followup. None of the 7 children had
recurrent UTI on followup. The authors suggested that DMSA could replace VCUG
as the primary evaluation for children following a UTI. VCUGs could be
selectively performed in children with abnormalities on DMSA scans and this
would reduce the number of VCUGs by about half based on the results of this
study. The same group conducted a further prospective study to test this
hypothesis [51]. In 290 children with UTI in infancy, 52 had VUR which was
dilating in 27.  An abnormal DMSA scan
was documented in 26 of the 27 children with dilating VUR. Tseng et al. also
attempted to answer this question whether a normal DMSA can obviate the need
for a VCUG following the first UTI [52]. In 142 children, only 5 children with
a normal DMSA scan had VUR (all less than or equal to grade 2) and no child
with dilating reflux had a normal DMSA scan. Table 1 summarizes these results.Table 1
Results of studies analyzing concordance between DMSA and VCUG findings.
Study (N)POS DMSA POS VCUGPOS DMSA NEG VCUGNEG DMSA POS VCUGNEG DMSA NEG VCUGHansson et al. (303)53 (17%)103 (34%)27(9%);≥III VUR in 7120 (39%)Tseng et al. (142)37 (26%)64 (45%)5(3.5%);≥III VUR in 036 (25%)Preda et al. (290)44 (15%)105 (36%)8(2.7%);≥III VUR in 1133 (46%)


## 4.4. Antibiotic Prophylaxis Does not Prevent Recurrent UTI in Children with Low-Grade VUR

The role of VUR, especially lower
grades, as a predisposing factor for recurrent UTI is also controversial. Nuutinen and Uhari noted a higher rate of
recurrent UTIs in children with grade III–V VUR in comparison with children
with grade I-II VUR [53]. It is now believed that the susceptibility for
recurrent UTI is more related to a defective urothelial defense mechanism and
bladder dysfunction rather than associated VUR. Roussey-Kessler et al.
conducted a prospective study on children with grade 1–3 VUR randomized to
receive cotrimoxazole or no treatment with UTI on followup as an end point [3].
There was no significant difference in the occurrence of UTI in both groups
except in boys with grade 3 VUR (P=.04). Garin et al. performed a
randomized prospective trial in 218 children with or without VUR who presented
with PN, comparing prophylaxis with no prophylaxis [2]. The study only included
patients with grade I–III VUR. No statistically significant differences were
found among the groups with respect to the rate of recurrent UTI, type of
recurrence, rate of subsequent pyelonephritis, and development of renal
parenchymal scars. The overall rate of recurrent PN in this study was 5.5% and
VUR did not increase the likelihood of PN. The authors concluded that at 1-year followup, grade I–III VUR did not increase the incidence of UTI, PN, or
cortical defects. Conway et al. performed a time-to-event analysis on 611
children who are presented with the first UTI to determine the association between antibiotic
prophylaxis and recurrent UTI and to identify risk factors for resistance [54].
The factors associated with an increased risk of recurrent UTI in this study
were white race, age between 3–5 years, and grade IV-V VUR. Sex and grade I–III
VUR were not associated with the risk of recurrence. Moreover, antibiotic
prophylaxis was not associated with a decreased risk of recurrent UTI in a
multivariable analysis but was a risk factor for antibiotic resistance among
children with recurrent UTI.The problem in interpreting studies
attempting to clarify this aspect is the lack of a standardized definition of a
febrile UTI and the variability in the methodology of obtaining urine samples.
The ongoing randomized intervention for children with vesicoureteric reflux (RIVUR)
study is a multicenter, double blinded, randomized, placebo controlled trial
which aims to answer the ongoing controversy regarding the role of antibiotic
prophylaxis in preventing recurrent febrile/symptomatic UTI in children with
VUR diagnosed after a UTI.In summary:(1)
in children presented with a UTI, up to 50% of children may have evidence of upper tract damage without evidence of VUR on a VCUG;(2)
the rate of spontaneous resolution of VUR is higher in children with low-grade VUR and a normal DMSA scan;(3)
a positive DMSA scan at diagnosis predicts a higher rate of recurrent UTI or breakthrough infections in children with VUR;(4)
VUR identification has not altered the ESRD rate related to reflux nephropathy.
The idea behind
these studies is to encourage a more selective approach in investigating
children who present with a first UTI, contrary to the AAP practice guidelines.
A DMSA would be the initial investigation and all children with an abnormal
DMSA will then proceed to a VCUG. This would identify the majority of children
with dilating/significant VUR who would then benefit from antibiotic
prophylaxis, thus reducing both the number of VCUGs and number of children on
antibiotic prophylaxis. Such a selective approach is justifiable with one
objection being that boys with a potential posterior urethral valve presented
outside the neonatal period may be missed with this approach. However, this may
be unlikely if a US study is simultaneously performed as part of the routine work up.


## 4.5. MR Urography (MRU)

MRU is increasingly being advocated
as a single imaging modality, which can be used to provide information obtained
on a VCUG and DMSA scan. The primary advantage of the MRU is its ability to
distinguish between renal dysplasia (congenital cortical defects) and acquired
scarring (acquired cortical defects) [55]. In addition to morphological
analysis, MRU can provide information about renal perfusion, concentration, and
excretion of contrast media by calculating the renal and calyceal transit
times. The Patlak differential function and the calculated Patlak number per mL
of renal tissue is considered a surrogate for the single nephron GFR and can
therefore serve as an important tool in prognosticating and following children
with renal dysplasia.


## 5. Followup Imaging for VUR

The ALARA (as low as reasonably achievable)
concept has stressed the importance of minimizing radiation exposure in
children being followed conservatively after diagnosis of VUR [5]. Thompson et
al. devised a theoretical model to study this and conducted a retrospective
study in children with primary VUR diagnosed after a UTI to evaluate different
strategies of followup and its effect on antibiotic exposure and cost [56]. The
authors recommended that children with mild VUR undergo a VCUG every 2 years
whereas those with moderate to severe VUR should undergo a VCUG every 3 years. In
a survey of the members of the American Association of Pediatrics published in
2001, 99% of the respondents indicated that they would perform a VCUG or RNC
every 12–18 months in followup [57]. The current followup protocol should aim
to reduce the number of VCUG/RNC performed while children are on antibiotic
prophylaxis basing it on the natural resolution decay curve of VUR. It is accepted
that all subsequent followup studies following a VCUG should be an RNC.


### 5.1. Factors Identified on Imaging which  Predict VUR Resolution

Persistence of VUR is more likely
in high-grade VUR, in children with bilateral disease (especially in Grade IV
and V) and when reflux is diagnosed in the older child. The value of the VCUG
and RNC in predicting VUR resolution has been studied. It has been demonstrated
that when VUR occurs at less than 60% of expected bladder capacity and the
reflux volume is more than 2% of bladder capacity, the resolution is poor
[58, 59]. Knudson et al. on a multivariate analysis stated that bladder volume
on initial cystogram of greater than 50% of predicted bladder capacity, age
younger than 2 years at diagnosis, and a history of prenatal hydronephrosis
were significant factors predicting VUR resolution within 2 years [35].


## 5.1. Factors Identified on Imaging which  Predict VUR Resolution

Persistence of VUR is more likely
in high-grade VUR, in children with bilateral disease (especially in Grade IV
and V) and when reflux is diagnosed in the older child. The value of the VCUG
and RNC in predicting VUR resolution has been studied. It has been demonstrated
that when VUR occurs at less than 60% of expected bladder capacity and the
reflux volume is more than 2% of bladder capacity, the resolution is poor
[58, 59]. Knudson et al. on a multivariate analysis stated that bladder volume
on initial cystogram of greater than 50% of predicted bladder capacity, age
younger than 2 years at diagnosis, and a history of prenatal hydronephrosis
were significant factors predicting VUR resolution within 2 years [35].


## 6. Conclusion

VUR is a heterogenous disorder, and
its diagnosis and management continues to remain one of the most controversial
problems in pediatric urology. There is a realization that rather than a
disease entity, VUR is a marker of overall urinary tract dysfunction, which may
predispose to UTI. The primary goal for the treating physician should continue
to remain preservation of renal function and preventing the relatively small
percentage of acquired renal defects associated with VUR. There has been a
paradigm shift in the earnestness with which the diagnosis of VUR is sought
after based on an increasing body of evidence which suggests that acquired
renal defects are often not related to VUR and that our current modalities for
diagnosing VUR are associated with unacceptable radiation exposure and bladder
catheterization. The newer modalities do hold promise but further work is
warranted before they can replace the existing well-established techniques.



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*Source: 367320-2008-08-28.xml*