Lippinccot

Vesicoureteral reflux is caused by primary or secondary

incompetence of the ureterovesical valve mechanism. During bladder
contraction, urine passes in a retrograde direction into the
ureter. The degree of reflux is graded according to the classification
system of the International Reflux Study (Table 19.3). Grading is
based on the appearance of contrast agent in the collecting system
during voiding cystourethrography (VCUG).
A. Incidence. Studies of asymptomatic children have estimated
an incidence of 17%, whereas vesicoureteral reflux is
present in 70% of infants with urinary tract infection. More importantly,
between 30% and 50% of children with reflux will
have renal scarring. Reflux is the second most common cause of
prenatal hydronephrosis and accounts for 37% of cases. Adults
with urinary tract infection (UTI) have a 5% incidence of reflux.
B. Etiology
1. Primary reflux is caused by lateral displacement of the
ureteral orifice during embryogenesis and a shorter intramural
tunnel for the ureter, resulting in a poor muscular backing.
A weaker valve mechanism is therefore available to close
the orifice during bladder contractions.
III. Vesicoureteral Reflux 357

2. Ureteral duplication is commonly associated with reflux

into the lower pole ureter, again owing to its abnormally
short intramural tunnel (see below).
3. Ureteral ectopia without ureterocele may be associated
with reflux.
4. Abnormalities of the bladder wall such as diverticula,
radiation cystitis, and cyclophosphamide (Cytoxan) cystitis
may predispose to vesicoureteral reflux. UTI may be associated
with transient reflux, due to the inflamed bladder wall.
5. Elevated intravesical pressure from any cause may
lead to reflux. Common causes are posterior urethral valves,
detrusor hyperreflexia, and prostatic enlargement in adults.
6. Prune-belly syndrome is a congenital condition characterized
by deficient anterior abdominal musculature, bilateral
cryptorchidism, bilateral megaureter, and often bilateral
vesicoureteral reflux.
7. Iatrogenic reflux may result from any surgical procedure
that disrupts the trigonal muscle, such as prostatectomy.
Resection of the ureteral orifice can also produce reflux.
8. Dysfunctional voiding or elimination syndromes can
lead to reflux. Voiding patterns should always be elicited in
the medical history.
C. Diagnosis. Vesicoureteral reflux rarely causes symptoms.
Most instances of reflux present as recurrent UTI or pyelonephritis.
In more advanced stages, the patient may present
with uremia or hypertension. The intravenous urography (IVU)
findings are usually normal in lower grades of reflux. The
VCUG is the definitive examination and must include a voiding
phase; in some cases, reflux may be seen only during the elevated
intravesical pressures associated with micturition. In addition,
in visualizing the urethra, the voiding phase of the VCUG
may allow the diagnosis of outflow obstruction to be made
(e.g., posterior urethral valves).
D. Treatment
1. Medical management is indicated in cases of low-grade
vesicoureteral reflux without outlet obstruction or another
abnormality. Good patient compliance is necessary. Longterm
antibiotic suppression with a regimen of amoxicillin
(neonate), trimethoprim/sulfamethoxazole, nitrofurantoin,
or other antibiotic agent at one-fourth to one-half the usual
dose daily is commonly used. Depending on the grade of reflux
as determined by VCUG, the age of the patient at diagnosis,
and unilateral versus bilateral disease, a considerable
number of instances of vesicoureteral reflux will resolve
spontaneously without surgical correction (Table 19.4). If the
patient remains asymptomatic, urine cultures are obtained
periodically (e.g., every 3 months) during treatment. US and
radionuclide cystogram should be obtained at yearly intervals.
If acute (“breakthrough”) infection occurs, a full course
of appropriate antibiotics is given and a prophylactic regimen
is then instituted. Some clinicians perform a dimercaptosuccinic
acid scan to look for renal scarring at this juncture.
Surgery is often recommended after breakthrough UTI.
2. Surgical therapy is indicated in patients with highgrade
primary reflux (grades 4 and 5), those with low-pressurereflux and significant hydroureter, and patients in whom medical
management has failed. Although failure can be defined
in various ways, most agree that persistence of reflux after
3 to 4 years of antibiotic prophylaxis, multiple “breakthrough”
infections, new or increased renal scarring, deterioration of
renal function, and noncompliance with medication are indications
for surgical therapy. In patients with minimal
hydroureter, creation of a ureteroneocystostomy with the
Leadbetter–Politano, Cohen, Glenn Anderson, or extravesical
techniques has a 98% cure rate. Approximately 1% of patients
have obstruction of the ureterovesical junction after ureteral
reimplantation that requires reoperation. In patients with
massive ureteral dilatation, tapering of the distal ureter may
be necessary during reimplantation. Rarely, temporary supravesical
diversion is necessary in patients who are severely
uremic.
.

Handbook
Vesicoureteral refl ux
Classifi cation and general information
VUR occurs when urine in the bladder fl ows retrograde
into the upper urinary tracts toward the
kidney(s). Infected urine can cause renal scarring and
renal insuffi ciency. The incidence of scarring is related
to the grade of refl ux. Sterile refl ux of urine does not
cause renal scarring after birth. However, antenatal
refl ux of urine can lead to renal dysplasia [11]. The
most common cause of pathologic antenatal hydronephrosis
is VUR, and children with a diagnosis of
persistent hydronephrosis after birth should undergo
VCUG to determine if VUR is present [12].
VUR is diagnosed by the visualization of contrast
in the upper urinary tracts on VCUG and is graded
as follows:
Grade I: distal segment of the ureter is visualized
Grade II: refl ux is visualized in the renal calices without
evidence of dilation
Grade III: mild dilation or blunting of the renal calices
Grade IV: dilated ureter and marked distention of the
renal pelves and calices
Grade V: severe tortuosity of the ureter and distention
of the calices and pelves
Epidemiology
VUR affects 1–5% of all children [13]. The age of
onset correlates to age of toilet training. VUR isp resent in 32% of affected individuals’ siblings [14].
Among daughters of affected females, 50% will have
VUR [15]. While males are more commonly found
to have VUR secondary to antenatal hydronephrosis,
the incidence of VUR is nearly four times higher in
females among those diagnosed after a UTI [16]. VUR
is found in 40% of children diagnosed with pyelonephritis
and 70% of infants diagnosed with UTI [17].
VUR is more prevalent among Caucasians compared
with African Americans.
Etiology
VUR is often secondary to a short intramural tunnel
length as the ureter enters the bladder. Normal filling
of the bladder causes mechanical compression of this
tunnel, thus preventing reflux. If the tunnel length is
too short or abnormally positioned, VUR may occur.
Secondary VUR occurs by increased intravesical
pressure from obstruction or inability to empty the
bladder. Treatment involves relief of the intravesical
pressure.
Renal scarring may occur in as much as 60% of
patients with UTI and VUR. Higher-grade refl ux
increases the likelihood of renal scarring. By- products
of infl ammation during infection result in local
ischemic changes direct tissue injury. If scarring is not
present by the age of 6 years, the risk of future scarring
is signifi cantly less. It is important to note that
renal scarring is the most common cause of pediatric
hypertension [18].
Diagnosis
Most commonly, VUR is diagnosed after the fi nding
of antenatal hydronephrosis or UTI. However,
careful history may also elicit other fi ndings commonly
associated with VUR, such as dysfunctional
voiding, constipation, fevers without diagnosis, and
fl ank pain.
Physical examination may reveal hypertension or
below-average height and weight secondary to renal
scarring. Other fi ndings include abdominal mass and
unrecognized neurological disease, such as sacral
depression or abnormal perineal sensation and/or
refl exes.
Urinalysis should be obtained in any patient suspected
of having UTI, VUR, or voiding dysfunction.
Pyuria and nitrites are indicators of infection andculture should be obtained. Proteinuria may be a
sign of renal damage. Rarely, serum creatinine can
be elevated in those children with profound renal
damage.
All children with a history of antenatal hydronephrosis
or UTI should undergo both renal ultrasonography
and VCUG. However, VCUG may be
traumatic for patients and requires radiation. The
decision to obtain a VCUG should be individualized
for each patient and his or her family. The diagnosis
of VUR can only be made after a VCUG is obtained
in suspected individuals. A nuclear cystogram can be
used to make the diagnosis; however, grading is only
possible with VCUG. Ultrasonography is useful only
to diagnose hydronephrosis and conspicuous renal
abnormalities. Suspicion of scarring can be diagnosed
with a DMSA renogram.
Treatment
Goals in the treatment of VUR include prevention
of UTI and renal scarring. Oftentimes, VUR will
resolve spontaneously. Generally, higher grade and
advanced age at diagnosis portend poorer resolution
rates compared to those who are diagnosed at
an earlier age or with lower grades of refl ux. VUR
in males is also more likely to resolve compared
to females. VUR is closely related to bladder and
bowel dysfunction. Those without bladder and
bowel dysfunction or those who have been successfully
treated also have a greater chance of spontaneous
resolution.
All children diagnosed with VUR should be
placed on antimicrobial prophylaxis until resolution
of VUR, surgical treatment, or among children
of advanced age who have no evidence of UTIs,
renal scarring, or bladder and bowel dysfunction.
Antimicrobial prophylaxis is effective in lowering
the occurrence of febrile UTIs among children with
VUR. Infants can be safely placed on amoxicillin
until 2 months of age. At that time, either nitrofurantoin
or trimethoprim–sulfamethoxazole can
be used with equal effectiveness. The choice of antimicrobial
may depend upon the patient’s allergies,
tolerance, side effects, resistance, and cost. While
other antimicrobials have been used successfully as
prophylaxis, it should be noted that nitrofurantoin
is the only antimicrobial agent that does not lead to
increased resistance among uropathogens. Surgical management is another treatment option
and represents defi nitive treatment. Indications
include breakthrough infections while on antimicrobial
prophylaxis, lack of compliance, failure of
VUR to resolve spontaneously with time, high-grade
refl ux with renal scarring or renal insuffi ciency, and
parental preference. The success rates of surgical correction
are high. Traditionally, ureteroneocystostomy
(UNC) or “ureteral reimplant” is performed either
through an intravesical or extravesical approach. The
principle of UNC is to ensure that the ureter passes
through the bladder wall with a length-to-diameter
ratio of at least 5:1. Success rates are roughly 98%
with this method [13]. The procedure can also be
accomplished with laparoscopy or robotic assistance
in experienced hands. UNC usually requires hospitalization
and urinary catheter following surgery. While
the procedure is usually well tolerated, complications
may occur along with prolonged hospitalization and
patient discomfort.
A less-invasive form of surgical treatment has
been used successfully in patients with VUR. Subureteric
injection of a bulking agent can be accomplished
endoscopically with minimal morbidity and
can be performed as an outpatient. The principle of
the procedure is to inject a bulking agent under the
mucosa of the ureteral orifi ce to improve coaptation.
Success rates range from 65% to 90% [19].
Generally, it is less effective with higher grades of
refl ux. Agents used for this procedure include dextranomer/
hyaluronic acid, collagen, Tefl on, and
silicone microspheres.
Treatment of VUR should be individualized for
each patient. Most young patients with low-grade
refl ux can be observed or maintained on antimicrobial
prophylaxis until resolution of refl ux. Children who
are older with high-grade refl ux usually will require
defi nitive surgical correction of the refl ux. Any child
with breakthrough UTIs or new renal scarring should
also undergo surgical correction.

Campbell

Intravesically, the inner muscle of the ureter merges with detrusor muscle to contribute to the superficial
trigone. Some of these inner ureteral fibers pass medially to contribute to the intraureteric ridge (Mercier bar).

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