The British Journal of Radiology, 80 (2007), 392–400

REVIEW ARTICLE

Vesicoureteric reflux in the adult

O BUCKLEY, MB, BCh, BAO, MRCPI, T GEOGHEGAN, MB, BCh, BAO, FRCR, J O’BRIEN, MB, BCh, BAO, MRCPI and
W C TORREGGIANI, MB, BCh, BAO, MRCPI, FRCR

Department of Radiology, Adelaide and Meath Hospitals incorporating the National Children’s Hospital (AMNCH),
Tallaght, Dublin 24, Ireland

ABSTRACT. Vesicoureteric reflux (VUR) is a well-recognized entity in the paediatric

population, but is not well described or understood in the adult population. This is
partly explained by the fact that its incidence declines with advancing age. Its diagnosis
is, however, still important, with VUR accounting for at least 10% of adult patients with Received 7 July 2006
Revised 24 September
end-stage renal disease. With early detection and careful management, the secondary 2006
complications of VUR such as renal failure can be prevented. Imaging plays a major role Accepted 20 November
in the detection and evaluation of VUR in the adult patient. Conventional techniques 2006
such as micturating cystourethrograms have now been supplemented by cross-sectional
DOI: 10.1259/bjr/60682848
imaging with CT and MRI. In this review article, we comprehensively review the up to
date status of imaging the adult patient with VUR and discuss important subgroups of ’ 2007 The British Institute of
patients such as pregnant and transplant patients. Radiology

Vesicoureteric reflux (VUR) is a well-recognized
condition in the paediatric population, but is less well
described in the adult population. The incidence of VUR
declines with advancing age and is 49% under 1 year,
26% under 12 years and only 4.4% in the adult
population [1, 2]. Despite this relatively low incidence,
it still accounts for at least 10% of adult patients
developing end-stage renal disease [3]. As well as renal
failure, VUR may also result in other secondary
complications such as hypertension, proteinuria, urinary
tract infections and renal calculi. Certain subgroups of
adults are particularly prone to VUR. These include
patients who have undergone cystectomy with ileal
conduit formation, transplant patients and patients with
a neuropathic bladder from spina bifida, for example. It
is also more common in pregnancy and more than half of
pregnant females with VUR experience complications
during pregnancy [4]. VUR is more common in the
female patient due to both the association of VUR with
pregnancy and the female urethra being predisposed to
infections. Females generally present with signs and
symptoms of urinary tract infection (UTI), whereas males
present with hypertension and signs of renal impair-
ment, such as proteinuria or hypertension.
Adults do not benefit from the childhood tendency for
VUR to improve with time and therefore secondary
complications will ensue over time if VUR remains
untreated [5]. With early detection and careful manage-
ment, the secondary complications of VUR, such as renal
failure, can be prevented. In this review, we describe the
presentation and diagnosis of VUR in adults, with
Address correspondence to: Dr William C Torreggiani, Department
of Radiology, Adelaide and Meath Hospital, Tallaght, Dublin 24,
Ireland. E-mail: william.torreggiani@amnch.ie or williammart@
hotmail.com
specific reference to subgroups of adult patients prone
to VUR such as pregnant females and transplant
patients. In addition, the role of the various imaging
modalities utilized in evaluating this disease will be
comprehensively reviewed.
Definition and incidence
VUR is defined as the retrograde flow of urine from
the bladder to the kidneys. It may be divided into
primary and secondary types, with primary VUR being
the predominant process. Primary VUR occurs in the
absence of any underlying pathology, while secondary
VUR in the adult occurs due to conditions such as
obstruction, previous surgical procedures or a neurolo-
gical disorder (Figure 1). It may also occur following
surgical procedures such as renal transplantation or
cystectomy with ileal conduit formation (Figure 2). VUR
is thought to occur in 1–2% of the general population,
with increased risk in siblings and children of affected
patients [6]. In most patients with congenital VUR, the
condition resolves before adolescence. The differentia-
tion between adult-onset and paediatric-onset VUR can
be difficult. However, many adults with VUR deny any
history of childhood UTI and report recent onset of
symptoms [7]. There is an estimated female:male ratio in
adults of up to 5:1 [8]. In the 60–70 year old age group,
there is a rise in the incidence of males with VUR, likely
to be due to the increased number of men under
investigation for bladder outlet obstruction [9, 10].
Renal transplant recipients can suffer from primary
and/or secondary reflux. VUR can occur into the native
kidneys and, if associated with persistent UTI, the
patient may have to undergo nephroureterectomy to
prevent an increased rate of infection post transplant

392 The British Journal of Radiology, June 2007

Vesicoureteric reflux in the adult
Figure 1. Micturating cystourethrogram in an adult patient
with known spina bifida and deteriorating renal function.
The bladder is irregular, in keeping with a neurogenic
bladder. There is free reflux seen in the left ureter (arrow).
[11]. In secondary cases, reflux of urine may occur
retrogradely up the newly implanted ureter (Figure 3)
and the clinical significance of this is controversial [12].
Pathophysiology
A family history of VUR is common, with a prevalence
of 4.7–51% in siblings of an affected child [13]. Advances
in genetic mapping have led to the localization of the
genetic abnormality to chromosome 1 [14]. The mechan-
ism of primary VUR is thought to be secondary to
weakness in the muscle of the trigone of the bladder,
which leads to the ureteric orifice lying in an abnormally
lateral position [15]. The ectopic location of the ureter
leads to a shortened course within the detrusor muscle.
Figure 2. Adult patient with previous cystectomy and ileal
conduit formation. Contrast has been infused into the ileal
conduit through a Foley catheter inserted into the proximal
portion of the conduit. Contrast is seen to reflux freely into
the right ureter and collecting system of the right kidney.
The British Journal of Radiology, June 2007
Figure 3. Single image from a micturating cystogram in a
patient post renal transplant. The transplant is located in the
right iliac fossa and contrast is seen to reflux into the
implanted ureter.
The valve becomes incompetent as a result when the
intravesical pressure rises on filling and micturition and
retrograde flow of urine ensues.
It is not well understood whether the pathophysiology
of primary VUR in the paediatric population is the same
as that found in the adult population, or whether adults
with VUR are simply congenital cases detected later in
life. About 35% of adults found to have VUR give a
history of previous UTI in childhood [14] and many
report recent onset of symptoms at the time of presenta-
tion [7]. Adults do not benefit from the childhood
tendency for VUR to improve with time [5]. In adults,
complications may often occur despite treatment as the
vesicoureteric junction does not develop as it does in
children and, as a result, the mechanism for reflux
persists [9]. The probability that the affected kidney will
become scarred is highest in infants and reduces with
age. The reason for this is not well understood. Theories
include a possible maturation process in the kidney that
protects from scarring, although this has not been
proven. With regard to adults, the onset and duration
of primary VUR is rarely known and secondary
complications such as scarring and nephropathy only
become apparent late in the disease process. Secondary
VUR results from disruption of the normal valve at the
ureteric orifice due to surgery or neurological problems.
In the renal transplant recipient, the likelihood of VUR
increases with time post transplant regardless of renal
implantation technique [16].
393
 O Buckley, T Geoghegan, J O’Brien et al

Clinical presentation
VUR may be asymptomatic. Overall, there are two
categories of adult presentation of patients with primary
VUR: (1) patients who have had VUR since childhood
that has remained undetected and presents in adulthood
with complications; and (2) patients who develop VUR
in adulthood de novo with no prior history of UTI. There
are differences in the way males and females present.
The majority of females diagnosed with VUR initially
present with a UTI [8]. Some females may be asympto-
matic and have incidental bacteriuria noted on urina-
lysis. The incidence of bacteriuria is more common in
females, probably due to the anatomy of the female
urethra [17]. Males more commonly present with
symptoms of complications of VUR and reflux nephro-
pathy such as hypertension and proteinuria [18]. Males
are often detected incidentally when they are being
investigated for other urinary symptoms [19]. When the
prevalence of VUR is assessed in patients undergoing
dialysis, the strong female-to-male preponderance is less
marked as many males present very late when already in
renal failure, whereas females are detected earlier. In-a
study of in-patients with hypertension and normal renal
Figure 4. Single image from a micturating cystogram in an
function, the incidence of VUR was as high as 19.1%,
adult female patient who presented with recurrent urinary
much higher than the incidence of VUR in the general tract infection (UTI) demonstrated unilateral reflux with
population (2%) [20]. This is a significant finding and dilatation of the right ureter.
should be considered when patients with hypertension
are being worked up as this is a potentially reversible according to a designated grading system. There are
condition. several classification systems of VUR. The International
Pregnancy and reflux nephropathy have profound Reflux Grading system is probably the best recognized.
effects on each other. More than half of pregnant females Depending on the degree of retrograde filling and
with VUR experience complications during pregnancy dilation of the renal collecting system as seen at
[4]. Physiological dilatation of the urinary tract and micturating cystogram, the International Reflux
increased glomerular filtration predispose the pregnant Grading system classifies VUR into five grades
woman with VUR to UTI, eclampsia and progression of (Figure 5) [23]. The severity of VUR is directly related
renal disease. Pre-conception renal function has a to the severity of scarring and the likelihood of
significant impact on pregnancy-related complications. complications. The limitations of this technique include
The detection of VUR in pregnancy should also prompt the fact that VUR is transient and the conditions that
the search for neonatal VUR in the subsequent offspring simulate it may not be reproduced at the time of MCUG.
due to the genetic nature of the condition.
N Grade I: Urine refluxes into the ureter only, with
normal renal pelvis and calyces
Imaging N Grade II: Urine refluxes into the ureter, renal pelvis
The best protocol for radiological investigation of VUR and calyces, but they appear normal
has been heavily debated over the years. Most of the N Grade III: Urine refluxes into the ureter and collecting
guidelines that do exist have been devised with reference system. The ureter appears mildly dilated and there is
to the screening for VUR in the paediatric population. evidence of some blunting of the calyces
With advances in radiology in non-ionizing modalities
such as ultrasound and MRI, the current guidelines may
gradually move to minimize the risk from ionizing
radiation [21]. Radiological techniques used to investi-
gate VUR include micturating cystourethrogram, radio-
nuclide cystography, intravenous pyelography,
ultrasound, CT and MRI.

Micturating cystourethrogram (MCUG)

MCUG is increasingly being used to investigate adults
with recurrent urinary tract infections to test for the Figure 5. Diagrammatic representation of the International
presence of reflux [9, 22]. Reflux can be unilateral Reflux Grading system. Vesicoureteric reflux (VUR) is classified
(Figure 4) or bilateral and the severity is classified into five grades. (Illustration courtesy of Tony Geoghegan.)

394 The British Journal of Radiology, June 2007

Vesicoureteric reflux in the adult
Figure 6. Spot film from a micturating cystogram in an adult
male who present with hypertension and renal impairment.
Urine refluxed freely into the ureters and collecting system,
and in this image the pelvis appears severely dilated and
calyces are severely blunted. The ureters appear very dilated
with a tortuous course.
N Grade IV: Urine refluxes into the ureter and collecting
system. Evidence of moderate dilatation of the ureter
and moderate blunting of the calyces
N Grade V: Urine refluxes into the ureter and collecting
system. The pelvis appears severely dilated and the
calyces are severely blunted. The ureter appears very
dilated with a tortuous course (Figure 6)
In cases of secondary VUR due to surgery such as ileal
conduit formation, contrast can be injected via the stoma
into the conduit, a procedure known as a loopogram. The
ureters can be affected by VUR with varying degrees of
severity, similar to that of primary VUR depending on
the calibre of the ureteric re-anastomosis (Figure 7).
Nuclear medicine
Nuclear medicine techniques permit direct and indir-
ect evaluation of VUR as well as assessment of renal
scarring secondary to VUR. With direct radionuclide
cystography, the bladder is infused with 500 ml of saline
mixed with 99mTechnetium-labelled sulphur colloid via a
catheter. The bladder is filled and the patient subse-
quently micturates under direct visualization of the
gamma camera. Any nuclide appearing in the ureters
and kidney is abnormal and diagnostic of reflux. Nuclear
medicine cystography is felt to be more sensitive than
conventional micturating cystography and has the
advantage of continuous imaging, unlike intermittent
fluoroscopy at MCUG [24]. With indirect radionuclide
cystography, a standard renogram is initially performed.
20 min following this, when the patient feels the need to
micturate, they are asked to do so in front of the gamma
camera. The radiolabelled urine in the bladder is
monitored and any amount of refilling at the end of
micturition is suggestive of VUR. This technique requires
the patient to have control of their bladder. Indirect
radionuclide cystography has been shown to be an
effective way of detecting VUR in young women who
The British Journal of Radiology, June 2007
Figure 7. Loopogram in a patient with an ileal conduit
performed following cystectomy for bladder cancer. There is
bilateral reflux into the ureters with evidence of ureteric
dilatation and calyceal clubbing secondary to the vesicoure-
teric reflux (VUR).
present with acute pyelonephritis [25]. With radio-
nuclide cystography, the severity can be assessed by
the levels of activities in the bladder, ureters and renal
pelvis. It is not easy, however, to transfer the grading
system used for assessing the severity of VUR on MCUG.
Technetium-labelled dimercaptosuccinic acid (DMSA)
is used to illustrate the size, shape and position of the
kidneys and also to identify scarring or thinning of the
cortex. DMSA scanning has a sensitivity of 79–86% in
detecting changes in the renal parenchyma of patients
with VUR and is more sensitive than ultrasound in this
regard [26, 27]. The changes seen at DMSA may be
transient in patients with acute pyelonephritis. DMSA
imaging also plays a complementary role to ultrasound
in the follow up of renal transplants. VUR is relatively
common in transplanted kidneys. Although it is con-
troversial as to whether VUR damages transplant
kidneys, both DMSA imaging for scarring and dynamic
renal scintigraphy scans using radiolabelled diethylene-
triamine pentaaceticacid (DTPA) or MAG-3 for renal
function are useful modalities to assess the transplanted
kidney.
Ultrasound
Ultrasound is an inexpensive, widely available tech-
nique that can be used to screen for reflux. Ultrasound
permits assessment of renal size, shape and cortical
abnormalities, as well as ureteric abnormalities
395

Figure 8. Sagittal ultrasound image in the pelvis demon-
strating dilated duplex ureters (arrow; left ureter) in a
patient with vesicoureteric reflux (VUR). (Asterix on bladder).
(Figure 8). A dilated system and scarring in the appro-
priate clinical context are predictors of reflux and, if
needed, patients may proceed to a formal MCUG.
Sensitivities have been recorded as high as 93% in some
studies [28]. In the 1970s, Tremewan et al initially
reported the use of ultrasonography in adult patients
with severe VUR [29]. Since then, there have been
advances in ultrasound technology that make it a more
sensitive means of detecting VUR, such as wide band
harmonic imaging and echo enhanced cystosonography
in the diagnosis of reflux [30, 31]. With this method, a
galactose suspension of fluid is instilled into the bladder
Figure 9. Intravenous pyelogram (IVP) in a patient with
secondary vesicoureteric reflux (VUR) due to a neuropathic
extrophic bladder demonstrates calyceal clubbing as a result
of VUR.
396
O Buckley, T Geoghegan, J O’Brien et al
Figure 10. Intravenous pyelogram (IVP) in a patient with a
horseshoe kidney shows evidence of chronic reflux nephro-
pathy with scarring of the renal cortex, grossly dilated
ureters and clubbed calyces bilaterally.
and the presence of reflux is detected by continuous
scanning. Advantages of this technique include the
absence of ionizing radiation as well as better anatomic
resolution compared with radionuclide studies. This
technique has been found to be as sensitive as MCUG in
the detection of VUR [32]. This technique is of particular
use in the adult population as there is better patient
cooperation than in the paediatric age group [28].
Figure 11. Post-contrast image of an intravenous pyelogram
(IVP) in a patient with vesicoureteric reflux (VUR) and
consequent reflux nephropathy demonstrates thinning of
the upper poles bilaterally due to scarring.
The British Journal of Radiology, June 2007
Vesicoureteric reflux in the adult
Figure 12. Transverse CT image following oral and intrave-
nous contrast in a patient with a horseshoe kidney and
vesicoureteric reflux (VUR). There is dilatation of the
collecting systems and scarring bilaterally.
Limitations of voiding ultrasonography include poor
sensitivity at detecting Grade 1 reflux as well as the
length of time required for the procedure. As in radio-
nuclide cystography, the grading system for contrast-
enhanced voiding ultrasonography is estimated by the
degree of microbubbles found in the ureter and the
pelvis, and if any dilatation is noted.
Intravenous pyelogram (IVP)
The role of intravenous pyelogram is rapidly decreas-
ing in assessing the patient with VUR. It may detect
secondary changes of VUR, but does not provide a
dynamic assessment of the refluxing urine. Secondary
changes include evidence of parenchymal scarring,
Figure 13. Three-dimensional gadolinium-enhanced source
image using a fast low-angled shot (FLASH) protocol in a
patient with vesicoureteric reflux (VUR) demonstrates marked
scarring of the lower pole of the right kidney. Non-enhancing
simple cysts are incidentally noted in both kidneys.
The British Journal of Radiology, June 2007
Figure 14. Coronal maximum intensity projection (MIP) in a
patient with a known horseshoe kidney image using a fluid-
sensitive half-Fourier single-shot turbo spin-echo (HASTE)
magnetic resonance urography protocol demonstrates a
Foley catheter in the bladder with dilatation of both ureters
and the collecting system of the kidneys in keeping with
reflux disease.
calyceal clubbing, ureteric dilatation and mucosal stria-
tions (Figures 9–11).
CT/MRI
CT with multiformat reconstructions can illustrate the
renal tract and any secondary changes that have resulted
from chronic VUR. Scarring is well seen (Figure 12) and
areas of active pyelonephritis, which occurs secondary to
VUR, may also be visualized. CT is superior to both
ultrasound and IVP in detecting focal parenchymal
abnormalities, defining the extent of disease and detecting
perinephric fluid collections and abscesses [33, 34]. CT
does, however, expose the patient to considerably more
radiation than other techniques for the evaluation of this
condition and it is not routinely used as a tool or
investigation of VUR. MRI on the other hand is a
radiation-free technique — a particular advantage when
the pregnant female requires evaluation. Magnetic reso-
nance urography (MRU) is useful in defining any
anatomical anomalies of the urinary tract that can
contribute to VUR, as well as evaluating renal cortical
scarring. In our experience, the addition of heavily T2
weighted single-shot turbo spin-echo (HASTE) sequences
results in MR urographic images that are highly fluid
397

(a)
Figure 15. (a) Coronal true FISP (fast imaging with steady-state precession) and (b) coronal maximum intensity projection (MIP)
image of a patient with unilateral vesicoureteric reflux (VUR) that has resulted in a small, shrunken right kidney.
sensitive and allow evaluation of the collecting system of
the urinary tract, particularly when the system is dilated
(Figures 13–16). Coronal and axial T1 and T2 weighted
sequences with and without intravenous gadolinium and/
or intravesical contrast provide both anatomical and
functional information. Voiding MR cystography is not
as sensitive as other techniques for detecting VUR, but it
can be useful where the risks of ionizing radiation must be
considered [35].
Treatment
Both surgical and medical options are available.
Surgical treatment includes reimplantation of the ureter
or injection of a synthetic polytetrafluoroethylene paste.
Medical treatment consists of antimicrobial treatment or
prophylaxis of UTI and treatment of hypertension. The
choice of treatment largely depends on the severity of the
nephropathy secondary to VUR and also the circum-
stances of the patient. Long-term antibiotic prophylaxis
may not be the ideal option for a younger patient in
whom more definitive treatment would be preferred. A
young patient with symptomatic UTI despite antimicro-
bial treatment is a relatively strong indication for surgical
intervention [36]. In a young female likely to become
pregnant, surgery may be the preferred option to avoid
potential pregnancy-related complications [37]. In cases
where severe renal scarring has already taken place,
398
O Buckley, T Geoghegan, J O’Brien et al
(b)
surgical treatment has not been shown to provide any
benefit [38, 39].
Clinical applications
No clinical guidelines exist for the evaluation of adult
VUR. In children, the American Academy of Paediatrics
advise MCUG and ultrasound for all young children
with first UTI [40, 41]. The role of DMSA in the
evaluation of first UTI in children remains controversial
[40]. Traditionally imaging of UTI in the adult is reserved
for those with complicated infections or immunocom-
promised patients [42]. The increased recognition of
adult VUR as a clinical entity should lead to physicians
investigating for the condition and the prevention of
VUR-related complications. Adult females with acute
pyelonephritis especially if of childbearing age represent
a group that would benefit from investigation for VUR
with ultrasound [43] and MCUG or direct radionuclide
cystography (DRC). Detection of VUR pre-conception
would enable treatment and/or careful management of
potential pregnancy-related complications. MRI and
ultrasound have an important role in the pregnant and
young adult female, and also in in utero detection of
VUR, as they have the advantage of lacking ionizing
radiation. Adult males with uncomplicated UTI may
benefit from investigation with ultrasound and MCUG
as, if VUR is missed, these males tend to present with
The British Journal of Radiology, June 2007
Vesicoureteric reflux in the adult
Figure 16. Coronal true FISP (fast imaging with steady-state
precession) image of a patient with spina bifida and
vesicoureteric reflux (VUR) secondary to a neuropathic
bladder, as evidenced by a dilated left ureter and clubbed
calyceal system.
significant delayed complications of VUR. Barai et al [20]
suggest that routine DRC should be included in the
evaluation of adults with hypertension as VUR is present
in 19% of adults with hypertension and normal renal
indices. Further studies on this subject are required to
create clearer guidelines for all.
Conclusion
Currently, there is great attention paid to both the
detection of VUR and the prevention of its secondary
complications in the paediatric population. It is generally
felt that children then outgrow the risks of VUR and that
this entity is not of major clinical importance in the adult
population. When the incidence of VUR is assessed in
adults with end-stage renal failure, it is found to be high
at 10%. Many of these adults have no prior history of UTI
or childhood VUR. Subgroups of the adult population
that suffer VUR and its complications include pregnant
females and renal transplant patients. Imaging plays a
key role in making the diagnosis and, although tradi-
tional modalities such as nuclear medicine studies and
micturating cystograms continue to play a key role in the
evaluation of VUR, cross-sectional imaging and espe-
cially MRI will likely play a greater role in the future.
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