VUR

nature reviews | urology aDvanCe OnLine PuBLiCatiOn | 1
reviews
Department of Urology,
University of iowa, iowa
City, iA, UsA.
Correspondence:
University of iowa,
Department of Urology,
200 Hawkins Drive,
3 rCP, iowa City,
iA 52242‑1089, UsA
christopher‑cooper@
uiowa.edu
Diagnosis and management of vesicoureteral
reflux in children
Christopher S. Cooper
Abstract | Critical evaluation of previously accepted dogma regarding the evaluation and treatment of
vesicoureteral reflux (vUr) has raised significant questions regarding all aspects of vUr management.
whereas the standard of care previously consisted of antibiotic prophylaxis for any child with vUr, it is
now unclear which children, if any, truly benefit from antibiotic prophylaxis. Operative intervention for vUr
constitutes overtreatment in many children, yet there are limited data available to indicate which children
benefit from vUr correction through decreased rates of adverse long‑term clinical sequelae. studies with
longer follow‑up demonstrate decreased efficacy of endoscopic therapy that was previously hoped to approach
the success of ureteroneocystostomy. Prospective studies might identify risk factors for pyelonephritis and
renal scarring without antibiotic prophylaxis. Careful retrospective reviews of adults with a history of reflux
might allow childhood risk factors for adverse sequelae to be characterized. Through analysis of multiple
characteristics, better clinical management of vUr on an individualized basis will become the new standard
of care.
Cooper, C. s. Nat. Rev. Urol. advance online publication 11 August 2009; doi:10.1038/nrurol.2009.150
Introduction
Over the last decade there has been increased recognition
that many children with vesicoureteral reflux (vur) do
not benefit from either diagnosis or treatment of their
condition.1
the disease in these children is self-limiting
and innocuous; however, a subset of children with
vur will benefit from both diagnosis and treatment.
Clarification of which children constitute this subset
remains the greatest challenge to the advancement of
vur management.
this review presents an overview and update of key
developments and controversies in the management of
primary vur, including incidence, etiology, clinical fea-
tures, the use of different imaging techniques in diagnosis
and follow-up of vur, and treatment options.
Background, incidence and etiology
vur is the retrograde flow of urine from the bladder into
the ureter. it occurs in approximately 1–3% of children
and is associated with 7–17% of children diagnosed with
end-stage renal disease worldwide.2–5
treatment of vur
is aimed at preventing the sequelae of pyelonephritis,
renal parenchymal injury, hypertension, and chronic renal
insufficiency.aperiodof30–40yearscanpassbetweenthe
first renal-scarring pyelonephritis and the development of
hypertension or end-stage renal disease.6
if the challenge
of identifying children that will benefit from diagnosis
and treatment of vur is to be met, long-term follow-up
of patients over the duration between the initial renal
insult and the clinically apparent sequelae is essential.
an estimated 30–40% of children under the age of
5 years who develop a urinary tract infection (uti) have
vur.5,7
vur can be further categorized as either primary
Competing interests
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author declare no competing interests.
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learning objectives
Upon completion of this activity, participants should be able to:
1 Describe the prevalence of vesicoureteral reflux (vUr) in the
general pediatric population and in children with urinary tract
infections.
2 Describe the grading system of the international reflux
study for classification of vUr.
3 Describe the inheritance pattern of vUr and guidelines for
its management.
4 Describe the efficacy of surgery for the management of vUr.
5 identify the most reliable tests for the diagnosis of vUr.
© 2009 Macmillan Publishers Limited. All rights reserved

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or secondary. Primary vur in children is frequently
attributed to an abnormally short intravesical tunnel
at the ureterovesical junction (Figure 1); the more severe
the abnormality, the worse the vur.8
secondary vur
occurs when reflux is induced by abnormally increased
bladder pressures, such as those seen with urethral
obstruction or neurogenic bladder dysfunction.
the severity of vur has been most commonly
reported using the classification of the international
reflux study (Figure 2).9
this classification defines
grade i as reflux into the ureter only, and grade ii as
reflux into a non-dilated pyelocalyceal system. Grade iii
vur demonstrates dilatation of the collecting system.
Grade iv involves more-extensive dilation with blunting
of the calyces and tortuosity of the ureter, and grade v
vur is associated with massive dilation of the collecting
system and severe tortuosity of the ureter.
in general, the severity or grade of vur has been used
as the main factor to determine the likelihood of sponta-
neous reflux resolution and risk of renal injury. Higher
grades of reflux are associated with decreased resolu-
tion rates and increased prevalence of renal scars.10,11
in
addition to grade, other factors have been shown to be
Key points
Many children with vesicoureteral reflux (vUr) do not benefit from either■
diagnosis or treatment of their condition
Prospective studies have not demonstrated utility of antibiotic prophylaxis in■
preventing urinary tract infections in many children with vUr
Prospective studies generally showed no difference in renal function or growth,■
progression or development of new scars, or urinary tract infections in those
treated by operative intervention versus prophylactic antibiotics
increasing grades of reflux and renal scars identify a higher risk group for■
subsequent renal damage and long‑term clinical sequelae
Better definition of children likely to benefit from intervention remains the■
greatest challenge to the advancement of vUr management
Management decisions are complex and require an individualized approach,■
taking into account numerous variables
predictive of reflux resolution and/or the risk of renal
injury. these factors include age, sex, laterality, bladder
volume and pressure at the onset of reflux, presence
of renal scars, presence of voiding dysfunction, and a
history of uti.12–19
the importance of vur as a factor leading to renal
injury due to infection was originally discovered in
patients with spinal cord injuries. when vur was
surgically corrected, patients had fewer problems
with pyelonephritis and urosepsis.20
this association with
renal injury or scarring secondary to vur is what led to
its discovery as a primary factor in children developing
pyelonephritis. subsequent studies demonstrated a lower
rate of new scars developing in children with primary
reflux compared to those with secondary reflux due to
neurogenic bladders or voiding dysfunction.21,22
Children with voiding dysfunction or dysfunctional
elimination not only have a higher incidence of break-
through infections while on antibiotic prophylaxis, but
also more renal scarring, a lower spontaneous resolu-
tion rate, and a higher failure rate following anti-reflux
surgery.23
as the chance of reflux resolution or renal
injury with secondary reflux is dependent on the type
and extent of bladder abnormality, it is now recognized
that secondary vur is more appropriately prevented
by improvements in the management of bladder dys-
function. Discussion of the management of neurogenic
or non-neurogenic bladder dysfunction is beyond the
scope of this review, which focuses on primary vur.
a strong inheritance pattern exists for primary vur.
the chance of a sibling of a child with vur also having
reflux is about 25%, and the offspring of affected indivi-
duals have a 27–51% increased risk of having reflux.24
the utility of sibling screening for reflux is questionable;
however, one study has noted that renal damage is more
prevalent in screened siblings with vur and a history of
uti compared to those without a history of uti.24
this
finding is consistent with the known increased risk of renal
scars developing in children with febrile utis who have
reflux. it remains to be demonstrated that detection and
management of vur in an asymptomatic screened sibling
will result in significantly decreased adverse sequelae and,
therefore, there is currently no consensus regarding the
practice of asymptomatic sibling screening for vur.
a lack of consensus also exists regarding the need to
screen newborns with a history of low-grade prenatal
hydronephrosis for vur. a study demonstrated that in
childrenwithahistoryofprenatalhydronephrosiswhohad
persistent grade ii hydronephrosis, identification of vur
and use of prophylactic antibiotics significantly reduced
the risk of febrile utis.25
reviewing similar data, others
suggest that mass screening and treatment of asymptom-
atic siblings of those with prenatal hydronephrosis pro-
vides little, if any, benefit, and is not cost-effective.26,27
these controversies emphasize that appropriate clini-
cal assessment and management of children with vur
requiresthetreatingphysiciantodevelopanindividualized
approach that considers multiple factors.
a b
x
Figure 1 | Diagram of the bladder submucosal tunnel. a | Normal submucosal
tunnel. Pressure in the lumen of the bladder increases as the bladder fills with
urine, compressing the ureter within the bladder wall (arrows), stopping reflux
(indicated by x). b | A short submucosal tunnel permits reflux as the section of
ureter in the bladder wall is not long enough to be compressed by rising pressure
in the filling bladder (arrows).

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Clinical management
Antibiotics versus operative intervention
several large prospective studies have attempted to
address the efficacy of operative intervention versus
antibiotic prophylaxis in children with vur.10,28–31
the
outcomes of these studies have generally demonstrated
that no significant differences exist in renal function or
growth, the progression or development of new scars,
or utis in patients treated with one intervention com-
pared to the other. Pyelonephritic symptoms, including
febrile utis, tended to be more common in the medically
treated groups compared with the surgical groups.32–34
in
general, new scars occurred earlier in children treated
surgically compared with those in the medical treatment
groups, but, as noted, no significant difference occurred
overall with longer follow-up in terms of new renal scars
in those treated with antibiotics compared to those
undergoing surgery.5,35
these observations suggested
that a potential benefit of anti-reflux surgery might be
a reduction in pyelonephritis in some patients; however,
other researchers suggested that, once renal scarring
occurs, the disease tends to run its course and operative
treatment has little benefit.6,36
a recent Cochrane review
concluded that nine re-implantation procedures would
be required in order to prevent one incidence of febrile
uti, with no reduction in the number of children devel-
oping any uti or renal damage.5
these studies reinforce
the need to better define the subset of children with vur
who might benefit from intervention.
Antibiotics versus observation
Multiple studies question the need for antibiotic pro-
phylaxis, indicating that, in selected individuals, the risk
of developing pyelonephritis and renal damage in the
absence of prophylactic antibiotics is low.32,37–39
Between
30% and 50% of children diagnosed with a uti will
suffer from a recurrence of infection. there is often an
incorrect assumption that vur is responsible for utis,
mainly because the diagnosis of reflux often follows a
uti. unless reflux is severe enough to induce stasis, it
does not predispose a child to developing utis.29,39
More
often, the infections are the result of predisposing condi-
tions, such as a previous history of utis, female sex,
constipation, infrequent voiding, incomplete emptying
and impaired host defenses.
although generally safe and well tolerated, daily anti-
biotic prophylaxis incurs financial costs and potential
health risks to children. antibiotic prophylaxis for reduc-
ing the likelihood of developing a uti has been associated
with a 24-fold increased risk of Escherichia coli devel-
oping resistance to trimethoprim–sulfamethoxazole.40
Other studies have demonstrated the emergence of
bacteria (aside from E. coli) with high rates of antibiotic
resistance in children receiving prophylactic antibiotics.41
Questions have also been raised as to the efficacy of
antibiotic prophylaxis for the prevention of utis.42,43
some investigators contend that antibiotic prophy-
laxis is safe and effective in the prevention of utis;44
however, antibiotic prophylaxis has not been proven
to reduce the incidence of pyelonephritis in children
with vur.
Because of the lack of proven efficacy and potential
adverse effects of antibiotic prophylaxis, several studies
have attempted to evaluate the efficacy of antibiotic
prophylaxis in children with vur. these studies have
included randomizing children with vur to observa-
tion or antibiotic prophylaxis.3,44–46
in general, these
studies failed to show a significant reduction in acute
pyelonephritis or renal scars in children with vur being
treated with antibiotic prophylaxis. some studies actu-
ally demonstrated an increased incidence of utis in
children receiving antibiotics, as well as an increase
in antibiotic-resistant bacteria causing the utis.3,44,45
By
subset analysis, other studies identified younger age and
increasing grade of reflux as risk factors for recurrent
febrile utis.44,47
Currently, there is an ongoing niH-
funded multicenter, randomized, placebo-controlled
trial (rivur trial) of prophylactic trimethoprim–sulfa-
methoxazole for children aged 2–72 months diagnosed
with grade i–iv vur after a first or second uti.23
it
seems likely that this large trial of 600 children will
confirm the findings of the smaller studies noted above,
and perhaps a subset analysis will identify characteristics
of children at the greatest risk for recurrent pyelonephritis
and development of new scars. unfortunately, as previ-
ously noted, the lag time between development of renal
injury and apparent clinical sequelae of hypertension
Normal Grade I Grade II
Grade VGrade III Grade IV
Figure 2 | international reflux Grading system.

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or renal insufficiency will require decades of follow-up to
characterize the group of children who may truly benefit
from intervention.
Clinical evaluation
Assessment of reflux
the only tests that routinely and reliably detect reflux
are voiding cystourethrography (vCuG) and nuclear
cystography. an initial vCuG provides better ana-
tomic details regarding reflux, including the presence
or absence of periureteral diverticuli, ureteral duplica-
tion, and abnormalities of the bladder, such as trabecula-
tions or urethral obstruction (Figure 3). the vCuG also
allows more-precise grading of reflux. typically, follow-
up studies are performed with nuclear cystography, as
there is a decreased exposure to radioactivity with this
study. Despite concern regarding exposure of the pelvic
organs to ionizing radiation during cystography in chil-
dren, there is little or no reported evidence suggesting
any future effect on gonadal function or an increased risk
of pelvic malignancies.
nuclear cystography reliably detects all grades of
vur.48
at the university of iowa, bladder pressures
are routinely monitored through a dual-lumen catheter
during the filling phase of a nuclear cystogram providing
a nuclear cystometrogram; however, this technique is not
widely used.18
this technique permits the measurement
of the intravesical pressure at the onset of reflux. using
this information, bladder pressure at the onset of reflux
was demonstrated as a predictor of spontaneous vur
resolution independent of the grade of vur.17
in addi-
tion to higher bladder pressure, independent predictors
of vur resolution on nuclear cystometrogram included
the onset of reflux occurring at greater instilled bladder
volumes, as well as reflux occurring during voiding
compared to filling.16
Catheterization can be a traumatic experience for a
young child. efforts to decrease the traumatic nature of
the procedure include the use of lubricants containing
local anesthetics and conscious sedation.49,50
typically,
cystography is repeated on a yearly basis; however, it
has been suggested that, for children in whom vur
is less likely to resolve, the interval between cysto-
grams should be longer in order to reduce exposure
to radiation, the number of traumatic studies, and the
associated cost.51
advances in the ability to predict
timing of spontaneous vur resolution should assist
the physician in determining the duration between
follow-up visits in order to minimize the number of
repeat cystograms.15,16,52
Assessment of renal scars
in a meta-analysis examining the presence of renal
damage in children hospitalized with uti, one study
found that approximately 34% of children with pyelo-
nephritis had vur, and of those with vur and
pyelonephritis, 72% had an abnormal dimercapto-
succinic acid (DMsa) scintigraphy findings (Figure 4).53
DMsa scintigraphy has been found to be a more sensi-
tive study than intravenous pyelography (ivP) for the
detection of reflux nephropathy.54
in addition, the scan
can detect changes of acute pyelonephritis with greater
sensitivity and specificity than Ct, Mri, or ultrasono-
graphy.55
Mercaptoacetyltriglycine (MaG3) has also been
used for renal imaging and has an improved capability in
the detection of renal scarring compared to ivP. renal
scans obtained by MaG3 imaging enable physicians to
determine a patient’s relative renal function, and show a
high degree of correlation with the relative renal func-
tion results determined by other types of renal scan.56
the DMsa scan is considered by many as the most
sensitive test for detection of renal scars; however, the
reported sensitivity rate of MaG3 imaging compared
to DMsa scintigraphy varies from 88% to equal to or
slightly better than a DMsa scan.56–58
the advantages of
MaG3 imaging compared to DMsa scintigraphy include
reduced radiation exposure, lower cost, and shorter time
requirements, as well as improved visualization of the
collecting system, which might improve specificity com-
pared to DMsa scintigraphy in children with marked
dilation of the collecting system.56
a b
Figure 3 | voiding cystourethrogram, demonstrating right‑sided reflux with a
periureteral diverticulum (arrows). a | The bladder is filled with contrast medium.
b | The patient has voided and emptied the bladder of contrast medium, although
some remains within the diverticulum.
a b
% RT LTANT RTLT POST%
83 82
0 0
Figure 4 | Dimercaptosuccinic acid scintigraphy with single photon emission
computed tomography imaging demonstrating a cortical defect in the upper pole of
the left kidney.

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reflux nephropathy and renal scarring
One-third of patients with vur have renal scars.33,59
the
presence of scars implies regions of renal damage, and
increases the risk of long-term adverse sequelae. in the
newborn with vur, however, scars associated with high-
grade reflux have been detected before the occurrence
of infection.60
these ‘congenital scars’ are thought to be
regions of focal dysplasia or hypoplasia resulting from
abnormal nephrogenesis as opposed to damaged normal
tissue following pyelonephritis. it is not known what pro-
portion of renal scars attributed to infectious injury are
actually due to abnormalities of embryogenesis. the ulti-
mate significance of these regions of dysplasia remains to
be determined; however, they are regions of diminished
renal function and can be associated with significant
morbidity and mortality.61
Children with pre-existing renal scars are more likely
to develop additional scars than children without renal
scars.62–64
a retrospective study of 120 patients demon-
strated a significantly higher chance of developing a
breakthrough uti in children with grades iii to v reflux
and an abnormality on baseline DMsa scintigraphy
compared to those without an abnormality (60% versus
6%).65
in one study with a mean follow-up of 12 years
after anti-reflux surgery, children with unilateral renal
scars had an 11% chance of developing hypertension
and an 18.5% chance if they had bilateral renal scars.66
Other investigators have suggested the incidence of
hypertension in children with bilateral renal scars is
about 20%.67
Children with severe bilateral renal scars
are significantly more likely to develop proteinuria,
chronic renal insufficiency and failure than those with
unilateral scars or unscarred kidneys.68,69
these data
strongly suggest that children with renal scars are at
an increased risk for further development of scars and
long-term clinical sequelae.
grade of Vur and renal scarring
Children with vur and concomitant utis are at an
increased risk of developing renal scarring compared
to children without vur suffering with utis. in the
international reflux study, 50% of children with vur
grades iii or iv had scars at study entry.54
several studies
have demonstrated a direct correlation between increased
prevalence of renal scarring and higher grades of vur.70
renal scarring develops less often in non-dilating forms
of reflux.61,62,71
the chance of developing further renal
parenchymal loss has also been shown to be higher in
children with grade iii or higher vur than in those
with grade ii or lower vur.31,72
renal scars have also
been demonstrated to be a negative predictor of reflux
resolution, independent of reflux grade.13
the association of renal scars with higher grades of
reflux and risk for subsequent scars, as well as decreased
resolution of vur, led some investigators to conclude
that the standard initial evaluation of a child with a febrile
uti should begin with a renal scan rather than vCuG.
Only in those children with an abnormal scan should
vCuG be performed. the benefit of such an approach
would be a reduction in the number of children under-
going vCuG and the identification of reflux in a higher
risk group. the use of ultrasonography instead of a renal
scan has been questioned because of the lower sensitivity
of the former, compared to renal scans, in diagnosing
renal scars. One study noted that up to 25% of patients
with cortical defects on DMsa scintigraphy had normal
ultrasound findings, providing further data regarding the
utility of renal scans in the evaluation of children with
febrile utis.73
Operative management
Endoscopic treatment of Vur
Following FDa approval of the use of dextranomer/
hyaluronic acid copolymer (DX/Ha) (Deflux®, Q-Med,
uppsalla, sweden) for the treatment of primary vur,
a growing number of parents and physicians began to
view endoscopic treatment of vur as an alternative
to beginning their child on an undefined duration of
prophylactic antibiotics (Figure 5).74
DX/Ha, a syn-
thetic mixture of dextran microspheres in a hyaluronic
acid gel, is the only commercially available injectable
treatment for vur in the us. the dextranomer par-
ticle size is larger than that of polytetrafluoroethylene
particles, which should prevent the complication of
lymphatic migration previously demonstrated with
polytetrafluoroethylene.75
although not as effective as open ureteral re-implanta-
tion, endoscopic correction of vur offers a mini-
mally invasive, outpatient procedure with a low risk of
complications. although a seemingly simple procedure,
several studies have demonstrated that a considerable
learning curve exists, with improved results obtained
with increasing experience.76–78
Other factors associ-
ated with successful endoscopic correction include a
lower grade of vur, lack of lower urinary tract voiding
dysfunction symptoms, increased volume of DX/Ha
injected, mound configuration following injection, and
surgical technique.78–80
a b
Needle
Bladder
Ureter
DX/HA
Figure 5 | endoscopic injection for vesicoureteral reflux. reproduced from Deflux®
patient education brochure (Q‑Med, Uppsala, sweden). Abbreviation: DX/HA,
dextranomer/hyaluronic acid copolymer.

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the short-term results of vur resolution following
a single endoscopic treatment with DX/Ha range from
59% to 95% per ureter treated.78
if patients undergo a
second injection for persistent vur, the success rate
is improved; however, studies have demonstrated that
a third injection is rarely curative.74,76,81
the long-term
efficacy of the endoscopic correction of reflux is not well
documented. a single long-term study documented a
persistent 95% efficacy in vur resolution in patients
treated with endoscopic polytetrafluoroethylene, with
a mean follow-up of 14 years.82
Most studies of DX/Ha
only report the results of cystography at 3 months or
1 year following the procedure. in studies using bovine
cross-linked collagen, the high failure rate did not occur
until years later, raising concerns regarding the long-
term efficacy of DX/Ha.83
Despite the relatively short
follow-up, recurrent reflux rates of between 11% and
26% occurring between 3 months and 12 months fol-
lowing a single DX/Ha injection have already been
reported.84,85
in a longer-term study of 49 patients who
had resolution of reflux at both 3 months and 12 months
after DX/Ha injection, 13% recurred at a mean of
3 years post-injection.76
the lack of durable success with DX/Ha has led some
researchers to suggest a need for continued monitoring
of children treated in this manner. aside from potential
failure of DX/Ha, calcification of the implant has been
reported as another potential long-term factor requiring
recognition.86
Mound calcification is not unique to DX/
Ha, and has been described with many endoscopically
injected agents.87,88
the chance of ureteral obstruction
following DX/Ha seems to be about 0.6%.89
ureteral re-implantation
the surgical treatment of vur has evolved over the past
50 years. a lower abdominal transverse incision is now
typically used, leaving a small scar in the skin crease
that frequently becomes inconspicuous. while multi-
ple different techniques for ureteral re-implantation
have been performed, most fall under one of two main
categories: intravesical surgery, in which the bladder
is opened and the ureters are dissected intravesically
(Figure 6a); and extravesical re-implantation (Figure 6b),
where the ureters are dissected away from the bladder
wall without opening the bladder and are left attached
1 2 3
1 2 3 4
a
b
Figure 6 | Common ureteral re‑implantation techniques for correction of
vesicoureteral reflux. a | intravesical Cohen ureteral re‑implantation.
b | extravesical Lich–Gregoir ureteral re‑implantation.
Figure 7 | User interface of a neural network for predicting
the chance and timing of spontaneous resolution of
vesicoureteral reflux based on a 2‑year resolution model.
Data input page.98

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to the bladder mucosa and re-implanted under flaps of
bladder muscle. there is no clear documentation of any
of the multiple techniques being superior to the others
in terms of vur resolution.10
improvements in analgesia, surgical techniques, and
the understanding that children undergoing ureteral re-
implantation for primary vur rarely need ureteral stents
or prolonged catheterization has reduced the length of
hospital stay and decreased morbidity associated with
the procedure.90
series of patients undergoing intra-
vesical and extravesical ureteral re-implantation surgery
as outpatients have been reported.91–93
recent studies
have documented the use of laparoscopic and robotic
ureteroneocystostomy in attempts to further reduce
perioperative morbidity.94
results of multiple series docu-
ment success rates with open ureteral re-implantation of
>95%, and close to 100% for lower grades of reflux.95–97
the procedures, however, carry the risks associated with
anesthesia and potential complications, including ureteral
obstruction, persistent reflux, infection and bleeding.10
Individualized management
the answers to many questions regarding vur remain
unknown; however, it is clear that definitive treatment
and even diagnosis of vur is unnecessary for many
patients. at present, the decision to operate on a child
with reflux or to continue or stop antibiotic prophy-
laxis is based on physician and parent assessment of the
associated risks and benefits. although this decision has
traditionally been based predominantly on the grade of
reflux, a truly informed decision must consider other
variables, including the patient’s age, sex, history of utis,
renal status, and the chance and likely timing of sponta-
neous resolution. a patient’s social situation and parental
preferences must also be factored in to the individualized
management analysis for a given child with vur.
in attempts to improve individualized patient manage-
ment, several reports from the university of iowa further
defined multiple prognostic factors relative to a child’s
chance of spontaneous vur resolution.12,13,16,17
One of
the predictive factors in these studies, independent
of vur grade identified by vCuG and nuclear cysto-
graphy, included the instilled bladder volume at the onset
of reflux. reporting the bladder volume at the onset of
reflux as additional predictive information should
become standard practice for those performing vCuG
or nuclear cystography.
trying to determine the chance and timing of sponta-
neous vur resolution in a given individual taking into
account multiple prognostic variables, such as age, sex,
grade of vur, bladder volume at onset of reflux, pres-
ence of dysfunctional voiding, history of utis, laterality
and duplication, becomes extremely complex. to this
end, a user-friendly neural network has been created and
is available online (Figure 7).15,98
the utility and accuracy
of this model was recently validated on an international
basis in a group of Japanese children.52
For children who
have had a renal scan, an updated computer model has
been generated that incorporates the additional renal
scan data to improve prognostic accuracy, and is available
at the same website.16
Conclusions
although improved accuracy regarding the chance and
timing of spontaneous vur resolution permits better
management decisions, additional information is needed.
Further studies are necessary in order to define an indivi-
dual child’s risk of subsequent pyelonephritis, renal
damage, and, ultimately, clinical sequelae. while ongoing
prospective studies, such as the rivur (randomized
intervention for Children with vur) trial, should help
define which children benefit from antibiotic prophy-
laxis, retrospective studies assessing long-term outcomes
in adults with a history of vur should be initiated in
order to better define those at the greatest risk of develop-
ing clinical sequelae. although retrospective studies have
limitations relative to prospective studies, well-designed
retrospective studies might minimize these limitations
and have the advantage of providing the information
required now as opposed to in 30–40 years’ time.
Review criteria
references were obtained by searching PubMed with
terms including “vesicoureteral reflux”, “children”,
“outcomes”, “incidence”, “etiology”, and “treatment”.
The references content and relevance to the points made
in this manuscript, as well as the author’s previously
published studies, personal experiences and interests also
influenced selection of the papers cited in this review.
1. Cooper, C. s. & Austin, J. C. vesicoureteral
reflux: who benefits from surgery? Urol. Clin.
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Acknowledgments
Désirée Lie, University of California, irvine, CA, is the
author of and is solely responsible for the content of
the learning objectives, questions and answers of the
MedscapeCMe‑accredited continuing medical
education activity associated with this article.

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