Vesicoureteric Reflux

Departemen
FK Unpad/RSUP Hasan Sadikin
 Embryology of the Ureterovesical Junction
The events proceed simultaneously to govern the position and integrity of the UVJ.
1
The embryonic ureter buds from the 4
Seminal embryologic work also
mesonephric (or Wolffian) duct to form
rotate relative once they contact the
the metanephric duct or early fetal ureter
UGS/bladder wall, resulting in the
2 ureteric orifice being proximal to the
The Wolffian duct and early ureter ejaculatory duct orifice
forming the two upper arms of a Y
with the distal mesonephric duct as
the stem of the Y 5
3 If the ureteric bud reaches the UGS too
soon, overrotation → inadequate
Incorporation continues until the entire
incorporation, insufficient intramural
stem is absorbed, leaving the two arms of
length in the bladder wall, and reflux
the Y to enter the bladder separately
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 Functional Anatomy of Antireflux Mechanism
1. For the purposes of reflux 3 .The intramural ureter
prevention, the ureter 2. Anatomic design of the UVJ. remains passively compressed
represents a dynamic conduit, At the heart of this unique by the bladder wall during
which propels a bolus of urine mechanism lies an intramural bladder filling, preventing
antegrade by neuromuscular portion of ureter that travels urine from entering the ureter.
propagation of peristalsis. within the detrusor muscle as it
traverses the bladder wall.

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 Functional Anatomy of Antireflux Mechanism
A. A refluxing
ureterovesical junction
has the same anatomic
features as a non-
refluxing orifice, except
for inadequate length
of the intravesical
submucosal ureter.

B. Ureterovesical junction
in longitudinal section.
1, Photomicrograph;
2, diagrammatic
representation.

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 Definition
Vesicoureteral reflux (VUR) is the retrograde flow of
urine from the bladder to the upper urinary tract.

➔ Vesicoureteric reflux is an anatomical and/or

functional disorder with potentially serious
consequences, such as renal scarring,
hypertension and renal failure.

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 Epidemiology
● Among infants prenatally
identified with hydronephrosis
● Vesicoureteric reflux is a
on US, who were screened for
very common urological
VUR, the prevalence was
anomaly in children, with an
16.2% (7-35%).
incidence of nearly 1%.
● Siblings of children with VUR
● Prevalence of VUR in non-
had a 27.4% (3-51%) risk of
symptomatic children has
also having VUR, whereas the
been estimated at 0.4-1.8%.
offspring of parents with VUR
had a higher incidence of
35.7% (21.2-61.4%)

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 Demography
Prevalence Gender

● Incidence higher relative rate in infants ● Higher rates of VUR in males over
0 to 12 months of age compared with females earlier in life, with prevalence
children 1 to 5 years. rates shifting with age
● Prevalence of reflux was estimated to ● A confounding factor is the sex-driven
be approximately 30% in children with predisposition to UTI:
UTIs and 17% in those who had ○ There is a 10- to 12-fold
imaging cystography for other reasons, increased risk for UTI in
such as hydronephrosis. uncircumcised infant males
○ Females have a higher propensity
for UTI after the first year of life
and in childhood relative to
males
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 Age

Demography ● Reflux is significantly more common in

younger children and may resolve
spontaneously over time.
Reflux in Fetus

● A VCUG in the newborn period are

limited to those with findings on renal
bladder ultrasonography (RBUS)
indicative of higher risk for significant
VUR
● Infants were screened with VCUG,
VUR was found in 10% to 40% and up
Race
to 19% having bilateral VUR.
● In old studies Up to a 10-fold
reduction in VUR in female children of
African descent was observed. More
recently, this difference appears to
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 Etiology
Primary Reflux Secondary Reflux

Caused by a fundamental deficiency Implies reflux caused by

in the function of the UVJ antireflux overwhelming the antireflux
mechanism while the remaining function of the UVJ
factors (bladder and ureter) remain - Resulting from sustained and
normal or relatively noncontributory. repeated increases in
intravesical pressures
Primary reflux represents a - Anatomic anomalies, such as in
congenital defect in the structure the case of duplication
and therefore function of the UVJ. anomalies and periureteral
Reflux occurs despite an adequately diverticulae.
low-pressure urine storage profile in
the bladder.

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 ➔ Sibling is male and the grade of reflux was high in the
index patient.

Risk Factor ➔ The incidence of VUR is much higher among children

with UTIs (30-50%, depending on age).
Defining and analysing the
risk factors for each patient ➔ Urinary tract infections are more common in girls than
(i.e. age, sex, reflux grade, boys due to anatomical differences.
LUTD, anatomical
abnormalities, and kidney ➔ Reflux trial has demonstrated LUTD in 34% of patients.
status).
➔ The presence of renal cortical abnormality, bladder
dysfunction, and breakthrough febrile UTIs are negative
predictive factors for reflux resolution.

➔ Patients with higher grades of VUR present with higher

rates of renal scars.

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Grading
Reflux
Five grades of reflux are used to depict the appearance of
the ureter, renal pelvis, and calyces as seen on the
radiographic contrast images generated by a VCUG.
Classification of
Ureteric Orifice Position
● Obstruction usually occurs in the caudo zone, and
ureters positioned in the cranio zone are likely to
result in reflux.
● Ureters positioned in the normal (N.) zone are
associated with normal kidneys.
● Because of ureteric bud abnormality, renal dysplasia
occurs with ureters projecting from both abnormal
positions.
Pathophysiology of
Renal Scarring Papillary Anatomy
The more polar calyces are composed preferentially
of compound papillae compared with the middle
Reflux provides a mechanical
calyces. The former are more commonly the site of
hydrodynamic mechanism that facilitates
the ascension of microorganisms from
intrarenal reflux (reflux into the ducts) and are the
the bladder to the kidneys. prime regions of susceptibility to scarring

Thus reflux may be considered an

accelerant for renal tissue infection after
bacterial colonization of the bladder.
Pathophysiology of
Renal Scarring

Hypertension
Host Susceptibility
Age There is obvious potential
for the cause of reflux- The fallout of these renal
The kidney’s predilection
associated hypertension to epithelial processes that is
for postpyelonephritic
rest with deranged renal the inflammatory response
scarring is inversely
microvascular mechanisms leads to local tissue
proportional to age.
associated with damage and scarring
parenchymal defects.
Pathophysiology of
Renal Scarring
Renal Growth
Correction of reflux will restore retarded
renal growth associated with reflux,
particularly when the growth defect is in
a unilaterally affected kidney
Renal Failure and Somatic Growth
The medical renal disease: hyperfiltration,
concentrating defects, proteinuria,
microalbuminuria, renal tubular acidosis,,
and increased fractional excretion of
sodium and magnesium.
Direct result of tubular and parenchymal
damage or dysplasia, concentrating defects
and increased concentrations of tubular
enzymes have been reported in the
presence of sterile reflux,
 Diagnostic Evaluation
1. Historical taking → medical history (including family history, and screening for LUTD
2. Physical exam
3. Laboratorium → urinalysis (assessing proteinuria), urine culture, and serum creatinine
4. Imaging
○ Standard imaging tests include renal and bladder US, VCUG and nuclear renal scans
○ Radionuclide studies for detection of reflux have lower radiation exposure than VCUG, but
the anatomical details depicted are inferior

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 Diagnostic Evaluation
Imaging (con’t)

● Dimercaptosuccinic acid
○ Best nuclear agent for visualising the cortical
tissue and differential function between both
kidneys.
● Video-urodynamic studies
○ Only important in patients in whom
secondary reflux is suspected
● Cystoscopy

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The VCUG is a fluoroscopic study that provides
information on both the functional dynamics and
structural anatomy of the urinary tract.
● Bladder contrast is instilled by gravity after
urethral catheterization at a maximum height
of 70 cm of water
● Bladder capacity is recorded when contrast
influx ceases
● Static images record bladder contour,
presence of diverticula or ureteroceles,
volume at which reflux occurs, grade of
reflux, configuration and blunting of calyces,
and intrarenal reflux, if present.
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VCUG
One should consider the presence of UVJ:
1. Dilated proximal ureter/not necessarily
kidney
2. Transition area to distal, aperistaltic
juxtavesical segment
3. Decrease in contrast caused by mixing with
trapped, nonopaque urine
4. Delay in drainage on postvoid film above
aperistaltic distal ureteral segment
 Infants presenting with prenatally
diagnosed hydronephrosis
Ultrasound of the kidney The degree of
and bladder is the first hydronephrosis is not a
Monitoring: The first reliable indicator for the
standard evaluation tool
two US scans within the presence of VUR, even
for children with
first one to two months though cortical
prenatally diagnosed
of life are highly abnormalities are more
hydronephrosis.
accurate for defining the common in high-grade
presence or absence of hydronephrosis.
renal pathology
Ultrasound should be
delayed until the first When infants who are diagnosed
with prenatal hydronephrosis
week after birth because
become symptomatic with UTIs,
of early oliguria in the further evaluation with VCUG
neonate. should be considered

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 Siblings and Offspring of Reflux Patients
The screening of asymptomatic siblings and offspring is controversial.

Prevalence of VUR
27.4% in siblings
35.7% in Offspring
Although early screening and therefore early diagnosis and treatment appears to be more effective
than late screening in preventing further renal damage,

Screening in all siblings and offspring cannot be recommended based on the available evidence.
The lack of RCTs for screened patients to assess clinical health outcomes makes evidence-based
guideline recommendations difficult.

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 Recommendations for
Pediatric Screening of VUR

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 Children with Febrile Urinary Tract

A routine recommendation of VCUG at 0 - 2 years of age An alternative “top-down” approach is

after the first proven febrile UTI is the safest approach as also an option,
the evidence for the criteria to selecting patients for
reflux detection is weak. This approach carries out an initial
DMSA scan close to the time of a
Children with febrile infections and abnormal renal US febrile UTI,
findings may have higher risk of developing renal scars
and they should all be evaluated for reflux. to determine the presence of
pyelonephritis, which is then followed
If reflux is diagnosed, further evaluation has traditionally by VCUG if the DMSA scan reveals
consisted of a DMSA scan. kidney involvement

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 Children with Lower Urinary Tract Symptoms and
Vesicoureteric Reflux
Reflux with LUTD resolves faster after
LUTD correction If there are symptoms suggestive of LUTD

Patients with LUTD are at higher risk for

e.g. urgency, wetting, constipation
developing UTI and renal scarring.
or holding manoeuvres

In LUTD, VUR is often low-grade and US

findings are normal,
An extensive history and examination,
The co-existence of LUTD and VUR means it including voiding charts, uroflowmetry and
would be better to do a test covering both residual urine determination, will reliably
conditions, such as a VUDS. diagnose underlying LUTD.

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 Associated Anomalies
& Conditions Reflux and ureteropelvic junction (UPJ)
obstruction
Ureteropelvic Junction
Obstruction A) Significant reflux fills the left ureter to
the level of the UPJ. Minimal filling of the
pelvis can be a sign of obstruction at this
The incidence of VUR associated with UPJO
level.
ranges from 0.6% in historical studies to as
high as 5.2% to 8.2% in more contemporary
studies.

Most of the patients with these two conditions

had reflux that was coincidentally discovered,
was of low grade, and resolved spontaneously
with time.
(B) In a different patient, reflux
is seen as the bladder fills.
(C) Significant kinking of the
UPJ occurs with voiding.

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 Associated Anomalies
& Conditions
Ureteral Duplication

VUR is the most common abnormality associated

with complete ureteral duplications.

The embryologic origin of the duplicated ureter

supports the observation that reflux occurs most
commonly into the lower pole.

The incidence of reflux is increased in patients with

complete ureteral duplication

In a series of 105 patients with complete duplication,

36% were managed nonoperatively with
Reflux into both ureters of a complete duplication, as shown here, is less spontaneous rates of reflux resolution of 85% for
common than reflux into the lower pole ureter alone. grades I and II, and 36% for grade III

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 Ureteral ➔ The Weigert-Meyer law states that ‘In a complete
ureteral duplication, the ureter whose orifice is more

Duplication medial and caudal reaches the upper moiety and the
other ureter whose orifice is more lateral and cephalad
(Associated reaches the lower renal moiety’.
Anomalies and ➔ Possible complication is double ureter and duplex
Conditions) system include obstruction, lithiasis, ureterocele and
VUR.

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 Associated Anomalies
& Conditions
Bladder Diverticula
The outpouching of mucosa between detrusor
muscle bundles, which lacks any true muscle backing
itself, commonly defining a bladder diverticulum, has
the theoretic potential to affect the natural history of
VUR.

Several retrospective studies demonstrate the high

rates of VUR in the presence of a paraureteral
bladder diverticulum and in a series of 131 children
with 202 refluxing ureters, 27% had a periureteral (A) Schematic representation of a bladder diverticulum
(2). A small amount of mucosa initially herniates through a congenital defect in the
diverticulum
bladder musculature. The defect enlarges with voiding.
Finally, the ureteric orifice (1) is incorporated into the diverticulum.

(B) Reflux into a right-sided paraureteral diverticulum and ureter seen on voiding
cystography

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 Associated Anomalies
& Conditions
Renal Anomalies
The development of both the UVJ and the kidney
itself are linked to the origin and fate of the ureteral
bud, it is reasonable to consider the existence of
reflux whenever an anomaly of renal form or number
is present.
Significant renal anomalies associated with reflux
are multicystic dysplastic kidney (MCDK) and renal
agenesis.
In the largest series to date, 75 patients with MCDK
showed a prevalence of contralateral reflux of 26%
(19 patients), and one-half of these were low grade
(1 to 2)
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Megacystic -Megaureter
Association
Massive bilateral VUR can cause a gradual
remodeling of the entire upper urinary tract. The
gross inefficiency of the bladder that expels urine to
both the exterior and the upper tracts results in
gradual bladder dilation as the refluxed urine returns
to the bladder.
This perpetuates marked ureteral dilation, leading to
the radiographic appearance of massive hydroureter
and a thin-walled enlarged bladder. The
phenomenon is referred to as the megacystis-
megaureter association or syndrome.
 Associated Anomalies
& Conditions
Other Anomalies
Some surveys reveals more than 40 different
syndromes in which VUR has been described. These
include :
VACTERL association (Vertebral, Anal, Cardiac,
Tracheo Esophageal, Renal, and Limb anoma- lies),
CHARGE syndrome (Coloboma, Heart disease,
Atresia choanae, Retarded development, Genital
hypoplasia, and Ear anomalies), and imperforate
anus.
In cases in which VUR is anticipated, a VCUG is the
initial study of choice to disclose both dysfunction at
the UVJ and overall bladder and bladder outlet
anatomy.
Pregnancy & Reflux
In summary, the majority of studies examining the
effects of VUR on pregnancy suggest that women
with a history of reflux have increased morbidity
during pregnancy because of infection- related
complications, whether the reflux has been
corrected or not.
Women with hypertension and moderate renal
impairment are also at risk for preterm birth. In
addition, 43% of their offspring who underwent a
VCUG had VUR.

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 Risk Factor and Risk Group
For Vesicoureteral Reflux
To better understand the specific child’s risk for infection in the context of
VUR and guide each patient’s care, identifying which factors need to be
modified to reduce each child’s risk profile, not only to prevent infection, but
also to decrease the intensity of treatment and follow-up when possible.

Example : An uncircumcised male child evaluated and found

to have BBD and intermediate grade VUR puts him at
intermediate risk for BUTI.

The clinician may opt to continue or start CAP until the BBD
and potential phimosis is confidently treated, at which point
the child’s risk might be considered to have been
downgraded and the risk for BUTI is sufficiently lowered
(from 28% to 8.6%) such that CAP can be safely
discontinued.

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 Disease Management

Non-Surgical Surgical
Therapy Therapy

Surgical treatment can be carried

The objective of conservative
out by endoscopic injection of
therapy is prevention of febrile UTI.
bulking agents or ureteral re-
implantation.

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 Non-Surgical
Therapy
VUR resolves
spontaneously, mostly in
young patients with low-
grade reflux.
VUR does not damage the
kidney when patients are free
of infection and have normal
LUT function.
Circumcision during early infancy → reducing the risk of infection
It is based on the understanding that:
Resolution is nearly 80% in
Spontaneous resolution is
VUR grades I and II and 30-
low for bilateral high-grade
50% in grades III-V within 4-
reflux.
5 years of follow-up.
Watchful waiting, intermittent or
No evidence that small scars
continuous antibiotic
can cause hypertension, renal
prophylaxis,
insufficiency or problems during
and bladder rehabilitation in
pregnancy.
those with LUTD
 Non-Surgical
Therapy

Regular follow-up with imaging studies (e.g. VCUG, nuclear cystography,

Follow Up or DMSA scan) to monitor spontaneous resolution and kidney status.

Prevention of recurrent UTI and renal scarring.

Trials show that, the benefit of CAP :

Continuous Antibiotic In low-grade reflux : NONE or MINIMAL

Prophylaxis In patients with grade III and IV reflux : USEFUL in preventing

recurrent infections but NOT PROVEN for preventing further
renal damage

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 Commonly Used
Prophylactic Antibiotics

Often, antibiotics Nighttime : allows antibiotic

The hallmark of observational therapy attempts
are given as oral concentration in the bladder
to decrease certain risk factors to prevent
suspensions once urine over the longest period of
infection and maintain urinary sterility through
per day and expected physiologic retention,
the judicious use of single daily low-dose CAP.
preferably at night. when infection is most likely
to develop.
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 Surgical
Therapy
Subureteric Injection of Bulking Materials
Using cystoscopy, a bulking material is
injected beneath the intramural part of the
ureter in a submucosal location. The
injected bulking agent elevates the ureteral
orifice and the distal ureter, so that
coaptation is increased → narrowing of the
lumen, which prevents reflux of urine into
the ureter, while still allowing its antegrade
flow.
The recurrence rate at two years after endoscopic treatment was
20%. The occurrence of febrile UTIs and scar formation was
highest in the surveillance group at 57% and 11%.

EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam 2022. ISBN 978-94-92671-16-5
Sung, J., & Skoog, S. (2012). Surgical management of vesicoureteral reflux in children. Pediatric nephrology (Berlin, Germany), 27(4), 551–561.
https://doi.org/10.1007/s00467-011-1933-7
 Surgical
Open Surgical Technique Therapy
The most popular and reliable open procedure is cross
trigonal re-implantation described by Cohen.

The ureters (the procedure is often bilateral) are mobilized

intravesically, and two separate submucosal tunnels are
created so that each ureter opens on the opposite side from
its hiatus.

The only disadvantage of the Cohen procedure is in the

event a ureteral retrograde catheterization becomes
necessary (for instance, to remove stones) due to the
orientation of the ureteral orifices.

Overall, all surgical procedures offer very high and similar

success rates for correcting VUR.
a Cohen procedure. The ureter is mobilized intravesically.
b Ureteral orifice at the end of the submucosal tunnel
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https://link.springer.com/article/10.1007/s00467-006-0415-9/figures/2
 The Other Procedures of
Open Surgical Technique Surgical
Therapy

EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam 2022. ISBN 978-94-92671-16-5
Sung, J., & Skoog, S. (2012). Surgical management of vesicoureteral reflux in children. Pediatric nephrology (Berlin,
Germany), 27(4), 551–561. https://doi.org/10.1007/s00467-011-1933-7
 Laparoscopy and Surgical
Robot-Assisted
The extravesical approach is the most commonly
Therapy
used.

Extravesical reimplantation does not differ from the

“open” Lich–Gregoir method (The juxtavesical
ureter is isolated, and the detrusor is incised
superior and lateral to the ureteral hiatus, creating
a submucosal bed of the ureter; the detrusor is
then sutured over the ureter)

Poor compared to open surgery and more invasive. Patient positioning and port placement. Ureteral Dissection
Operative times, costs and post-operative
complications leading to secondary interventions
are higher, but post-operative pain and hospital
stay is less compared to open surgery.

Highlighting the Length of detrusor tunnel, Placement of running detrusorraphy

placement of U stitch, and use of Apical alignment suture, with inclusion of the ureteral
EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam 2022. ISBN 978-94-92671-16-5 suture. Adventitia.
Gundeti, M.S., Boysen, W.R., & Shah, A.B. (2016). Robot-assisted Laparoscopic Extravesical Ureteral Reimplantation:
Technique Modifications Contribute to Optimized Outcomes. European urology, 70 5, 818-823 .
 Complications Surgical
Complications of open surgical repair include obstruction (2%) and contralateral
Therapy
reflux (9%).

Two cases of clinically significant complications following the endoscopic

treatment of vesicoureteral reflux, showed that the reflux persisted, advanced
clinically and was accompanied by persistent UTI, which was resistant to
pharmacotherapy. The histopathological examination of the abnormal masses
removed from the area of the VUJ confirmed the presence of a long-lasting
inflammation, the formation of granulomas, and pseudocysts around the
Deflux® (the frequently used synthetic material) injection site.

Laparoscopic Procedure complications including ureteral injury/obstruction,

urine leak, and fistula, have precluded widespread adoption.

Sung, J., & Skoog, S. (2012). Surgical management of vesicoureteral reflux in children. Pediatric nephrology (Berlin,
Germany), 27(4), 551–561. https://doi.org/10.1007/s00467-011-1933-7

Zyczkowski, M., Prokopowicz, G., Zajęcki, W., & Paradysz, A. (2012). Complications following endoscopic treatment of
vesicoureteric reflux with Deflux(®) - two case studies. Central European journal of urology, 65(4), 230–231.
https://doi.org/10.5173/ceju.2012.04.art12
Resolution
Spontaneous Resolution
At birth, the probability of spontaneous
resolution of primary reflux is roughly inversely
proportional to the initial grade.
If a patient is encountered at a later age,
resolution from any point in time forward will
depend on initial grade of reflux, if it is known,
and age at presentation.
Reflux likely resolves spontaneously as a result of
remodeling of the UVJ over time
Resolution by Grading
Most cases of low-grade reflux (grade I and II) will
resolve. Several studies have documented this high rate
of spontaneous resolution (Variance for grade II : 63%,
80%, and 85%)
Grade 3 reflux will resolve in approximately 50% of
cases
Very few cases of higher-grade reflux (grades 4 and 5,
and bilateral grade 3) will resolve spontaneously (no
more than 25% and as little as 9%)

Resolution
Resolution by Age
The age at which reflux begins or is first encountered will
play a more important role in the management of the
patient with reflux than the grade itself.
Reflux is a congenital disorder → most prevalent in
neonates and young children → demonstrate the greatest
tendency to resolve in this group.
Other large studies suggest that diagnosis at 5 years of
age and in infancy is associated with a similar resolution
rate (20% per year), regardless of age (Connolly et al.,
2001)
The initial 1997 AUA guidelines provided a synthesis of
large numbers and reasonable statistical estimates of
resolution rates segregated by age and grade →
revised in 2010 → validated in 2017
(A) Percent chance of persistence of
grades 1, 2, and 4 reflux for 1 to 5
years after initial evaluation.
(B) Percent chance of persistence of
grade 3 reflux by age for 1 to 5 years
after initial evaluation.
Provide a similar picture for resolution rates of VUR and
refocus the importance of identifying patients that would
benefit from screening based on several potential risk factors,
beyond age
 The Essential Tenets of
Reflux Management
1. Spontaneous resolution of reflux is very common and facilitated by correction of BBD.
2. Higher grades of reflux are less likely to resolve spontaneously, especially when diagnosed in
older children after UTI.
3. Sterile reflux is unlikely to cause significant renal damage.
4. Prevention of UTI is more important than VUR resolution.
5. The use of prophylactic antibiotics is safe and beneficial, particularly in high-risk patients.
6. There is a role for medical management for most forms of reflux.
Summary of Evidence and Recommednation for the
Management of Vesicoureteric Reflux in Childhood
2. Examples
By the end of this section, your audience should be
able to visualize:

➔ What
What is the pain you cure with your solution?

➔ Who
Show them a specific person who would
benefit from your solution.
Thank You!