EUROPEAN UROLOGY SUPPLEMENTS 11 (2012) 16–24

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Vesicoureteral Reflux

Guy A. Bogaert *, Koen Slabbaert

Urology – Pediatric Urology, UZ Leuven

Article info Abstract

Keywords: In the past 30 yr, the therapeutic approach to children with vesicoureteral reflux
Vesicoureteral reflux (VUR) has undergone a dynamic evolution from mainly surgery, as soon as VUR was
Urinary tract infection detected, toward a conservative approach with antibiotic prophylaxis (stimulated
Pediatric and supported by results from the International Reflux Study in Children), to an
Bladder dysfunction endoscopic approach, and to the currently used active surveillance approach
Antireflux surgery without prophylaxis. During those 30 yr, the diagnostic approach has not changed
as much, although there is always an attempt to make the diagnosis of VUR while
avoiding the ‘‘classic’’ voiding cystourethrogram (VCUG), which is one of the most
stressing exams for a child and his or her family.
Initially, radiographic grading of VUR was the only method of measuring the
severity of VUR and of calculating the chance of spontaneous resolution. However,
several other factors such as age, sex, presence of bladder and/or bowel dysfunc-
tion, presence of associated anatomic abnormalities, and laterality have been
shown to have an influence on the spontaneous resolution rate.
Based on the results of recent randomized studies (PRIVENT, Randomized
Intervention for Children with Vesicoureteral Reflux [RIVUR], Swedish reflux
study) and the updated VUR guidelines from the American Urological Association
and the European Association of Urology–European Society for Pediatric Urology,
this review will give an overview of the important clinical features of VUR, the
diagnostic methods, the computer models and nomograms to detect which chil-
dren with VUR should be treated, and the options their respective chances of
success for treating patients. It will become clear that the treatment selection and
decision for treating VUR in a child is an individualized process.
# 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author.
E-mail address: guy.bogaert@uzleuven.be (G.A. Bogaert).

1. Introduction diagnostic approach has not changed as much, although

In the past 30 yr, the therapeutic approach to children with
vesicoureteral reflux (VUR) has undergone a dynamic
evolution from mainly surgery, as soon as VUR was
detected, toward a conservative approach with antibiotic
prophylaxis (stimulated and supported by results from the
International Reflux Study in Children), to an endoscopic
approach, to the currently used active surveillance ap-
proach without prophylaxis. During those 30 yr, the
1569-9056/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
there is always an attempt to make the diagnosis of VUR
while avoiding the ‘‘classic’’ voiding cystourethrogram
(VCUG), which is one of the most stressing exams for a
child and his family.
Initially, radiographic grading of VUR was the only
method of measuring the severity of VUR and of calculating
the chance of spontaneous resolution. However, several
other factors such as age, sex, presence of bladder and/
or bowel dysfunction, presence of associated anatomic
doi:10.1016/j.eursup.2012.01.006
 EUROPEAN UROLOGY SUPPLEMENTS 11 (2012) 16–24
abnormalities, and laterality have been shown to have an
influence on the spontaneous resolution rate. In 1981, John
Woodard, a world expert opinion leader on VUR, stated, ‘‘As
one looks back over the last 30 years of reflux history, it is
ironic that urologists have become so expert at its surgical
correction before understanding much about its natural
history and true clinical significance’’ [1]. Without doubt,
his statement is still true today.
Based on the results of recent randomized studies
(PRIVENT, Randomized Intervention for Children with
Vesicoureteral Reflux [RIVUR], Swedish reflux study) and
the updated VUR guidelines from the American Urological
Association (AUA) and the European Association of Urology
(EAU)–European Society for Pediatric Urology (ESPU), this
review will give an overview of the important clinical
features of VUR, the diagnostic methods, the computer
models and nomograms to detect which children with VUR
should be treated, and the options and their respective
chances of success for treating patients. It will become clear
that the treatment selection and decision for treating VUR in
a child is an individualized process.
2. Symptomatology
Clinical symptoms due to VUR can be symptomatic or
asymptomatic. Symptoms can be recurrent urinary tract
infections (UTIs) with and without fever. Recurrent UTIs are
due to incomplete emptying of the bladder with urinary
stasis caused by the VUR and subsequent risk of bacterial
colonization and bacterial ascension. In smaller children,
failure to thrive or recurrent otitis media can mask and
delay the diagnosis of VUR. Sudden onset of urge and urge
incontinence with or without bowel dysfunction in older
children and otherwise ‘‘dry’’ children can also suddenly
reveal VUR. The voiding symptoms will often result in a
dysfunctional elimination syndrome and may add bowel
dysfunction, such as constipation, to the problem. The
constipation will worsen the incidence of bacteriuria or
recurrent UTIs. Voiding dysfunction as such, without
clinical UTI, can be one of the first signs of VUR.
Asymptomatic features are a family history of VUR or
findings on ultrasound such as hydronephrosis, hydrour-
eteronephrosis, renal parenchymal changes, renal dyspla-
sia, or hypoplasia. However, a difficult question remains in
the event of an abnormal technetium Tc 99m dimercapto-
succinic acid (DMSA) isotope renal scan: Is it (congenital)
renal dysplasia or (acquired) renal parenchymal damage?
The recent Swedish reflux study has found some interesting
results [2]. At the beginning of the prospective randomized
trial, 124 of 201 children had an abnormal renal DMSA scan.
Symptoms of parenchymal damage were found in 30 of
128 girls (23%) and 44 of 75 boys (59%). After 2 yr, new renal
parenchymal damage was found in 11 of 49 children (22%)
with recurrent UTIs and in 4 of 152 children (3%) without
recurrent UTIs.
If VUR is suspected or should be excluded, the diagnostic
work-up should be performed using as few examinations as
possible and with special respect for radiation exposure.
Indications for the following work-up are one febrile UTI in
17
boys or girls, one proven nonfebrile UTI in boys, or recurrent
nonfebrile UTI in girls [3]. Clinical exam, height, weight, blood
pressure, serum creatinine, urinalysis for proteinuria
and bacteriuria, a urine culture, and sensitivity are recom-
mended [3,4]. A renal ultrasound is considered a noninvasive
exam that provides information on both kidneys with regard
to renal structure and function; however, in the work-up of a
child with a UTI, a renal ultrasound cannot be considered a
specific exam predicting VUR [5]. The importance of voiding
dysfunction as a prognostic factor in the resolution rate of
VUR was mentioned by Schwab et al in 2002 [6] and was
confirmed more recently in the prospective Swedish Reflux
Trial [7]. It is important to include a voiding diary, (several)
uroflowmetry studies, and residual volume measurements in
the work-up for VUR.
A classic radiologic VCUG, using modern digital en-
hanced techniques, is still the standard exam demonstrat-
ing VUR, timing and laterality of the reflux, grade of reflux,
exact anatomy of the upper and lower urinary tracts
(duplication, paraureteral diverticula), voiding phase, and
anatomy of the bladder outlet and urethra. Examples of
VCUG and the grading system according to the International
Reflux Study Committee are demonstrated in Figure 1 [8].
There is no doubt that VCUG is an exam that causes distress
and anxiety for the child and his or her family; however, to
date, no alternative exam provides all of the information
previously mentioned. Midazolam combined with simple
analgesia is an effective method to reduce distress in
children undergoing VCUG without interfering with the
voiding dynamics [9]. Indirect methods of VCUG using
intravenous isotopes require continent children and pro-
vide images with much lower quality than conventional
fluoroscopy. Urosonography using a contrast-enhanced
medium can eliminate radiation exposure but requires
special expertise of the pediatric radiologist and the
placement of a catheter and will not provide the urologist
with specific images regarding anatomic specificities such
as renal duplication [10]. A direct VCUG using isotopes as a
contrast medium does not eliminate the stress of catheteri-
zation and cannot reach the excellent imaging quality of
conventional radiology. A possible future modality to screen
noninvasively for VUR could be microwave heating of the
urine in the bladder and measuring the temperature in the
kidneys [11,12].
A renal DMSA scan is part of the work-up of every child
with a proven VUR or a febrile UTI. The renal DMSA scan is a
static examination that images the functional distal tubules
of the kidney and allows demonstration of small parenchy-
mal damage [13]. In addition, the renal DMSA scan is
important for follow-up; therefore, it is important that
DMSA should be combined with the chromium-51
ethylenediaminetetraacetate (EDTA) isotope, allowing the
measurement of the exact glomerular filtration rate (GFR)
and calculation of the single-kidney GFR. This split renal
function in combination with the anatomic images will
allow the clinician to make a correct statement if one kidney
has improved or deteriorated [14].
Both studies, classic VCUG and DMSA scan, are necessary
and complementary in the work-up of a child with VUR.
18 EUROPEAN UROLOGY SUPPLEMENTS 11 (2012) 16–24
[(Fig._1)TD$IG]

Fig. 1 – Clinical examples of the International Reflux Study in Children vesicoureteral reflux grading system: (a) Left-sided grade II and right-sided grade III
(note the voiding phase, allowing judgment of the bladder neck and the moment of high voiding pressure in the image); (b) left-sided grade III and right-
sided grade IV; (c) left-sided grade IV and right-sided grade II (note the bilateral paraureteral Hutch diverticula); (d) bilateral grade V.

Several studies have tried to identify patients who
underwent either a DMSA scan or a VCUG and who would
not require the other exam, but it is a fact that there are
children without VUR and with renal damage and children
with VUR and without renal damage. Consequently, it is not
possible to identify ‘‘not dangerous’’ VUR looking only at a
DMSA scan [13,15].
Initially, Rubenstein et al introduced a novel but (still)
controversial technique to identify VUR in children
presenting with febrile UTIs and a negative VCUG:
positional instillation of contrast (PIC) cystography. This
cystogram is performed by positioning the cystoscope close
to the ureteral orifice with the bladder empty and instilling
contrast in a gravity-aided manner from a height of 1 m
using the irrigation port of the cystoscope [16]. The
argument that this technique could induce VUR in anyone
was countered by using a control group of children without
UTI and VUR in whom the PIC cystogram did not
demonstrate reflux. It was a logical step from undetected
contralateral VUR to situations in which we suspect VUR
but are unable to demonstrate it. It is a well-known
phenomenon that, most frequently, girls suffering from
 EUROPEAN UROLOGY SUPPLEMENTS 11 (2012) 16–24 19

Table 1 – Grading system for vesicoureteral reflux, according to the International Reflux Study Committee [8]

Grade I Reflux does not reach the renal pelvis; varying degrees of ureteral dilatation
Grade II Reflux does reach the renal pelvis; no dilatation of the collecting system; normal fornices
Grade III Mild or moderate dilatation of the ureter, with or without kinking; moderate dilatation of the collecting system;
normal or minimally deformed fornices
Grade IV Moderate dilatation of the ureter, with or without kinking; moderate dilatation of the collecting system; blunt fornices
but impressions of the papillae still visible
Grade V Gross dilatation and kinking of the ureter, marked dilatation of the collecting system; papillary impressions no longer
visible; intraparenchymal reflux

recurrent UTIs with or without renal parenchymal scars on
the DMSA scan will have a negative VCUG. In these patients,
PIC cystography can reveal undetected VUR, and appropri-
ate treatment has been proven to reduce the incidence of
UTIs [17,18].
Biomarkers are a point of research but are not clinically
relevant today [19]. Intravenous pyelography should not be
performed because it does not add relevant information and
uses radiation. Videourodynamic studies should be re-
served for patients in whom secondary reflux is suspected,
such as those with neuropathic bladder dysfunction or boys
whose VCUG is suggestive for posterior urethral valves.
3. Pathophysiology
Is there a difference in VUR in a duplex system? In
general, <1% of the general population has a duplex kidney,
and VUR is the most commonly associated anomaly found
in duplex kidneys, especially in those presenting with a UTI
(70%) [25]. VUR almost always occurs in the lower pole
moiety, due to its lateral entry and shorter intravesical
pathway. If VUR is also seen in the upper pole, one must
suspect an incomplete duplication or an ectopic orifice in
the bladder neck or urethra and misplacement of the
transurethral catheter at the time of the VCUG. VUR in
duplex kidneys can resolve, but it will take longer than in a
single system. Surgery, including the eventual correction of
the ureterocoele of the upper pole, is challenging but
provides excellent results [26].

The incidence of VUR in neonates varies between 0.5% and
1%. However, in children with a proven febrile UTI, the
incidence of VUR is 30–40%, with a female predominance of
4:1 if the child is >1 yr of age [20]. At <1 yr of age, VUR is
more frequent in boys.
VUR is defined as the nonphysiologic retrograde flow of
urine from the bladder up the ureter into the kidney and is
the result of an insufficient vesicoureteral junction. The
severity of VUR is measured using the grading system
according to the International Reflux Study Committee
(Table 1) [8]. Primary or congenital VUR is caused by a
congenital maldevelopment of the vesicoureteral junction,
which is too short and has a possible lack of a fixed
attachment between the ureter and the detrusor [21]. Based
on observations of incidence of VUR among siblings and
twins, it is now known that primary or congenital VUR is
autosomal dominantly inherited and is polygenic with
variable penetrance and expressivity [22,23].
The recommendations for screening in siblings are from
both the AUA [4] and the EAU [3]: The parents of a child with
VUR should be informed about the higher incidence among
siblings. It is recommended that a renal ultrasound be
performed in siblings that are not toilet trained. If the renal
ultrasound shows any abnormality, VCUG is recommended.
If no ultrasound screening is performed, special attention
for UTI and early treatment should be initiated, followed by
a complete investigation for VUR. Secondary reflux devel-
ops under the influence of anatomic or functional infra-
vesical obstructions due to inflammatory or neuropathic
disorders of the bladder. Although most children with VUR
will have excellent long-term prognosis, a small group has a
significant risk. This risk can be minimized in areas with
good medical health care where prompt diagnosis and
treatment of acute UTI is possible [24].
4. Indications for treatment
The goals of management of the child with VUR are
prevention of recurrent febrile UTIs, prevention of renal
injury, and minimization of the morbidity of treatment and
follow-up [4]. The choice or advice for treatment will
depend on several individual parameters such as gender,
age of the child, grade of reflux, laterality, symptoms, renal
function, renal damage, associated functional bladder and/
or bowel problems, compliance, and choice of the parents
[27]. There are mainly two methods of treatment:
conservative (waiting for spontaneous resolution) or
interventional (minimal or surgical). If a child presents
with breakthrough UTIs or renal damage several years after
conservative waiting, this will determine the treatment
option, with its advantages and disadvantages, that will be
chosen by the parents and the doctors (Table 4).
The AUA guidelines make a clear distinction for children
<1 yr of age (Table 2), whereas the EAU-ESPU guidelines
mention ‘‘childhood’’ and have three age categories: <1 yr
of age, 1–5 yr of age, and >5 yr of age (Table 3). It is
recommended that the possible advantages and disadvan-
tages of every treatment option be listed, as mentioned in
Table 4.
5. Surveillance
A surveillance treatment method combines watchful wait-
ing without medication or additional treatment as well as
antiseptic or antibiotic prophylaxis and treatment of the
dysfunctional elimination syndrome.
Prophylactic antiseptic or antibiotic treatment is based
on the hypothesis that neither VUR as such nor a lower UTI
20 EUROPEAN UROLOGY SUPPLEMENTS 11 (2012) 16–24

Table 2 – Management of the child with primary vesicoureteral reflux according to the American Urological Association guidelines [4]

<1 yr of age History febrile UTI grade I–V
No history febrile UTI grade III–V
No history febrile UTI grade I–II
>1 yr of age Grade I–V with bladder/bowel
dysfunction
Grade I–V without bladder/bowel
dysfunction
Continuous AB prophylaxis:
recommended
Continuous AB prophylaxis:
recommended
Continuous AB prophylaxis:
offered
Bladder/bowel dysfunction
treatment (not specified)
Continuous AB prophylaxis:
recommended
Continuous AB prophylaxis:
considered (in the event of renal
cortical abnormality)
Consider circumcision
Consider circumcision
Consider circumcision
If on AB prophylaxis plus breakthrough infection, then
option of endoscopic or surgical VUR correction (if no renal
scar possible, change AB prophylaxis);
if not on AB prophylaxis, then start AB prophylaxis
If on AB prophylaxis plus breakthrough infection, then option
of endoscopic or surgical VUR correction (if no renal scar
possible, change AB prophylaxis); if not on AB prophylaxis,
then start AB prophylaxis

AB = antibiotic; UTI = urinary tract infection; VUR = vesicoureteral reflux.

Table 3 – Management of the child with primary vesicoureteral reflux according to the European Association of Urology guidelines [3]

<1 yr of age Grade I–V Continuous AB prophylaxis: Advise circumcision in low-grade VUR
recommended
1–5 yr of age Grade I–III Continuous AB prophylaxis: If on AB prophylaxis plus breakthrough infection or noncompliance with AB
recommended prophylaxis or new renal scars or associated malformations, then recommend
endoscopic or surgical VUR correction
Grade IV–V Endoscopic or surgical –
VUR correction: recommended
>5 yr of age Boys No treatment If UTI, then recommend endoscopic or surgical VUR correction
Girls Endoscopic or surgical –
VUR correction: recommended

AB = antibiotic; UTI = urinary tract infection; VUR = vesicoureteral reflux.

is harmful to the kidney. However, a UTI in a situation of
VUR presents a real chance of renal damage. Recent
randomized controlled trials suggest that antibiotic pro-
phylaxis offers no advantage over intermittent antibiotic
therapy for UTIs in terms of prevention of recurrent UTIs or
new renal damage [28]. However, under the age of 1 yr, it is
recommended and has been demonstrated in the recent
prospective randomized controlled Swedish reflux trial that
UTIs can be prevented using prophylaxis [29]. Beyond the
age of 1 yr, mainly girls will benefit from prophylaxis [2,29].
The choice for antiseptic or antibiotic treatment is also
age dependent. For a child <3 mo, cefaclor 15 mg/kg of body
weight or trimethoprim 2 mg/kg of body weight should be
given once daily, preferably at night. For a child >3 mo,
nitrofurantoin 2 mg/kg of body weight or trimethoprim
2 mg/kg of body weight should be given once daily,
preferably at night. Trimethoprim is still recommended,
but a relative higher incidence of resistance toward
Escherichia coli of 33% is known [30].
Sillén et al have shown that bladder dysfunction in young
infants exists and is associated with a higher incidence of
UTI and renal scarring [7]. Schwab et al have clearly
demonstrated in a 15-yr retrospective study that the
spontaneous resolution rate in grade I–III is 13% per year
and drops thereafter to 3.5% (exponential curve); in grade
IV–V, it is only 5% [6]. The authors recommend performing
an early correction for grade IV–V from 18 mo on. Ismaili
et al concluded in an earlier report for the EAU-EBU Update
Series on VUR that long-term antibiotic prophylaxis does
not fully prevent UTI and renal scarring [24]. This has been

Table 4 – Advantages and disadvantages of treatment options

Advantages Disadvantages

Surveillance Chance of spontaneous resolution (grade I–III: 13% per year; Risk of renal damage (febrile UTI)
grade IV–V: 5% per year)
Continuous Chance of spontaneous resolution (grade I–III: 13% per year; Risk of renal damage (febrile UTI)
AB prophylaxis grade IV–V: 5% per year) Questionable intake compliance
Development AB resistance
Endoscopic correction Outpatient procedure Variable: 70–90% (long-term) success rate
Minimally invasive procedure Follow-up VCUG necessary
Surgical correction Immediate and permanent success 2–3 days in hospital
Low complication rate Surgical procedure morbidity
No follow-up VCUG necessary

AB = antibiotic; UTI = urinary tract infection; VCUG = voiding cystourethrogram.

 EUROPEAN UROLOGY SUPPLEMENTS 11 (2012) 16–24
confirmed in the RIVUR and the Swedish reflux study. Based
on the greater morbidity of UTIs in children <1 yr of age,
continuous prophylaxis is recommended [4].
Children with functional bladder and/or bowel dysfunc-
tion should undergo specific treatment, together with their
parents, with drinking and voiding recommendations,
relaxed and correct voiding conditions at regular intervals,
eventual double voiding, biofeedback of the pelvic floor
muscles, anticholinergic medication in the situation of
overactive bladder, healthy food recommendations, and
eventual pharmaceutical support for regular bowel move-
ments. These recommendations are part of ‘‘empathic
doctoring’’ and may require regular follow-up by a
urotherapist or doctor. However, whether treatment of
voiding dysfunction influences the resolution rate of VUR in
children remains unclear and would require prospective
randomized trials [31].
Possible advantages and disadvantages of conservative
treatment are summarized in Table 4.
A clear disadvantage or possible danger is the fact that
compliance of children with VUR taking (or should we
rather say, ‘‘being given by their parents’’) prophylaxis is as
low as 40% [32].
6. Minimally invasive treatment
O’Donnell and Puri in 1984 were the pioneers for the
endoscopic correction of VUR using Teflon as a bulking
agent [33]. Their original technique was called STING, for
subureteral polytetrafluoroethylene (Teflon) injection. Very
soon after the first injections, studies in animal models
found migration and granulomatous reaction after periur-
ethral injection of polytetrafluoroethylene [34]. Strangely
enough, this did not stop the original pioneers from
injecting polytetrafluoroethylene into ureters and bladders,
and years later, they reported continuous good results and
no complications [35]. However, the possibility of migration
has urged more suitable and safer bulking agents.
Collagen, crosslinked collagen, autologous lipocytes,
chondrocytes or myoblasts, coaptite, and several other
bulking agents have been tested and proposed. Today,
however, only dextranomer microspheres and hyaluronic
acid of nonanimal origin (Deflux) and solid silicone
elastomer suspended in a water-soluble, bioexcretable
carrier gel (Macroplastique) are approved by the US Food
and Drug Administration and are used commonly as bulking
agents. So far, both implants are stable long term, remain in
position, and do not disappear over time. In addition, the
particles are too large to be able to merge into capillaries or
lymphatics.
The success rates of the STING injection technique
(70–85%) have never reached those of surgical correction.
However, Kirsch et al [36] introduced the intraureteral
injection technique after hydrodistention of the ureter, a
technique they popularized while trying to categorize the
refluxing ureters by flushing the ureteral orifices with the
cystoscope and its flushing channel. Kirsch et al were able to
improve the success rates of the endoscopic injection
technique by another 10% (reported success rate up to 90%)
21
[37]. Depending on the grade of VUR, the ultimate success
rate for the individual patient will be determined by the
injection technique, the injected volume, the mound
morphology and location, the abnormal anatomy and/or
physiology (eg, as in renal duplication), the presence of
dysfunctional voiding, and the experience of the surgeon.
Another unanswered question in the endoscopic treat-
ment for VUR is the long-term efficacy of the bulking agent.
One of the unclear results from the recent Swedish reflux
study was the fact that the children in the endoscopic
treatment group with Deflux had the highest success rate of
VUR resolution and the lowest incidence of UTIs but with
one of five children presenting with a recurrence of dilating
VUR after 2 yr [38]. It is necessary for children having an
endoscopic treatment for VUR to undergo regular follow-up
with the possibility of VCUGs. It is also important to discuss
all possible advantages and disadvantages of the endoscopic
technique with the child and his or her parents (Table 4). In
summary, the endoscopic treatment was initially developed
as an alternative to open surgical correction, but today it
is considered an alternative to long-term prophylactic
treatment [27].
7. Surgical treatment
The first surgical treatment one should think of in the event
of a newborn boy with VUR should be circumcision. Singh-
Grewal et al found in a meta-analysis of 12 studies that
circumcision definitely reduces the risk of UTI [39].
However, in normal boys, the number needed to treat
(NNT) to prevent one UTI is 111. In boys with recurrent UTI
or high-grade VUR, the risk of UTI recurrence is 10% and 30%,
respectively, and the NNTs are 11 and 4, respectively. The
authors concluded that, assuming equal utility of benefits
and harms, net clinical benefit is likely only in boys at high
risk of UTI.
Surgical correction of VUR, by definition, creates an
antirefluxive valve mechanism for the ureter. Placing the
ureter in a long or longer channel between the submucosal
layer and the detrusor can create this antireflux valve
mechanism. Dewan described in a review article how the
different ureteral reimplantation techniques have evolved
over time [40]. Creation of a longer intramucosal tunnel can
be performed intra- or extravesically, by open surgery,
laparoscopically, or by using robotic instrumentation. This
is the fastest and most successful method to correct VUR in
>95% of cases. The main benefit of surgical correction is the
fact that the incidence of febrile UTIs is significantly
decreased, and this has been shown in studies comparing
different treatment strategies [41,42].
Indications for surgical correction are breakthrough UTIs,
renal function impairment (preexisting or developing under
surveillance or prophylactic treatment), associated ana-
tomic anomalies (renal duplication with upper pole
ureterocoele, paraureteral diverticulum), problematic pa-
rental compliance, and parental preference.
The intravesical cross-trigonal ureteral reimplantation
(Cohen) is probably the safest and perhaps the most widely
used surgical technique for the correction of VUR [43].
22 EUROPEAN UROLOGY SUPPLEMENTS 11 (2012) 16–24
However, this technique is always on the table for
discussion, along with possible difficulties for eventual
ureterorenoscopy later in life. The incidence of ‘‘later in life’’
issues that would require endoscopic intervention are
extremely rare but are nevertheless possible [44]. The
technique described by Politano-Leadbetter is an excellent
method for ureteral reimplantation, but its complication
rate is higher (up to 7–10%) than the cross-trigonal
technique [45]. The psoas-hitch ureteral reimplantation
deals with an even higher rate and more severe complica-
tions and should be reserved for repeat interventions or
specific indications [46,47].
The extravesical ureteral reimplantation technique
described by Lich-Grégoir is very popular because it has
excellent success rates and is associated with low morbidity
[48]. However, due to the possible pelvic plexus damage
during the extravesical dissection and the consequent
possible temporary voiding dysfunction, it is recommended
that this technique be performed unilaterally and eventu-
ally repeated in a second step on the contralateral side [49].
Intravesical cross-trigonal and extravesical ureteral
reimplantation have been performed successfully using
laparoscopic techniques [50,51]. Recently, these techniques
have also been performed using the assistance of robotic
techniques [52,53]. It has been proven that it is feasible to
perform surgical correction using laparoscopy or robotic
assistance, although it has to be proven if there is any
benefit for the patient.
8. Outcome, follow-up, and recommendations
The risks and benefits of diagnosing VUR are questioned
today in terms of health and financial impact: What is the
benefit of prescribing long-term prophylaxis? VUR is a
clinical symptom that is not based on a simple disease but
on a number of factors influencing the expression of the
symptom and its consequences. Sex, age, renal function,
voiding dysfunction, grade, laterality, associated anatomic
anomalies, and genetic factors will determine how danger-
ous VUR will be for renal development and function
[54–56]. The management of children with VUR has
changed, and large studies (the International Reflux Study
in Children, the PRIVENT study, the RIVUR study, and the
Swedish reflux study) have helped influence our current
opinion and treatment strategy [57–60].
The treatment strategy for children with VUR should be
individual for every child. It should be based on several
coexisting factors such as age, sex, laterality, grade of reflux,
presence of voiding dysfunction, and renal damage.
Computer models and nomograms should be used to
analyze the child’s specific situation and should be
discussed with the parents.
The computer-based model was created using a large
database of VUR patients. It can be used to predict VUR
resolution at 2 yr of age and is available on the UroComp
Web site (http://www.urocomp.org/; select SVM/VUR out-
comes) [61]. This computer model was validated in a
separate patient population in Japan and was found to have
81% accuracy with a receiver operating characteristic value
of 0.79 [62]. In addition, an updated version, using
additional renal scan data, further improves the predictive
accuracy (http://www.urocomp.org/; select SVM/VUR out-
comes using renal scan data [updated]) [63].
Nomograms predicting the percentage of VUR resolution
at 1–5 yr are based on a large patient population at Children’s
Hospital Boston [56]. These nomograms use age, sex,
laterality, clinical presentation, ureter anatomy, and grade
of reflux and are available through a Web-based calculator
(http://www.childrenshospital.org/vurcalculator).
Wheeler and colleagues in a 2004 Cochrane review [41]
and Nagler and colleagues in an updated review in 2011 on
the interventions for VUR [42] performed meta-analyses of
combined long-term antibiotic prophylaxis and surgical
corrections. Both groups found that with the end points of
UTI incidence, new or progressive renal damage, renal
growth, hypertension, and GFR, the only difference was that
surgical treatment resulted in a 60% reduction in febrile
UTIs by 5 yr compared with antibiotic prophylaxis alone.
However, this difference did not result in a difference in the
risk of parenchymal injury. It is not clear whether any
intervention does more good than harm, although some
data show a dramatic decrease in reflux-related morbidity
with an aggressive approach [64].
Should the first investigation following a febrile UTI be a
DMSA scan or a VCUG? Regarding the diagnostic approach
or suspicion of VUR, after the obligatory renal ultrasound, it
is still requisite to perform a radiographic VCUG and a
DMSA scan, regardless of the results of either. Febrile UTIs
and acquired cortical defects can occur without VUR,
cortical defects in children with VUR will predict recurrent
UTI, and a positive DMSA scan identifies significant VUR in
most instances [65]. However, better knowledge of which
patients might benefit from early treatment may limit the
number of children required to undergo VCUG [66]. The
exact indication and value of the PIC cystography has to be
determined. In addition, alternative noninvasive methods
may identify the correct patients [12]. In the event of a
family history or siblings with VUR, if asymptomatic and
under the age of 5 yr, a renal ultrasound should be
recommended. However, if a child with a family history of
VUR becomes symptomatic, a classic VCUG and an isotope
DMSA scan should be an immediate part of the evaluation.
In the follow-up of children with VUR, as few procedures as
possible and as minimally invasive procedures as possible
should be the absolute rule [65].
With regard to increasing resistance of E. coli strains and
the relatively low compliance with prophylaxis intake, the
treatment strategy should include options such as circum-
cision and subureteral or intraureteral injections in an early
phase of diagnosis. Girls, more frequently a little older,
should receive empathic doctoring, consisting of modified
drinking habits, appropriate voiding and bowel recommen-
dations, and close follow-up.
It is interesting that the AUA and EAU-ESPU guidelines
for VUR mention endoscopic treatment as a possible
surgical correction, whereas it is clear from all studies that
an endoscopic treatment is an alternative to the antibiotic
prophylaxis [27]. A lot of studies and publications on VUR
 EUROPEAN UROLOGY SUPPLEMENTS 11 (2012) 16–24
are known, but good prospective and randomized con-
trolled studies are still necessary to improve the work-up
and the optimal management of children with VUR [42].
9. Conclusions
VUR and its evolution will depend on different factors;
therefore, VUR is an individual problem for every single
patient. Work-up with renal and bladder ultrasound;
VCUG, including voiding images; a DMSA scan; and
eventual voiding and bowel diary will facilitate the correct
diagnosis. In the first year of life, circumcision should be
offered for boys and antiseptic or antibiotic prophylaxis
should be recommended. Thereafter, individual calculation
of the chance of spontaneous resolution using computer
models and nomograms will help the clinician and the
parents of children with VUR choose the best option for
treatment.
Conflicts of interest
The authors have nothing to disclose.
Funding support
None.
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