Vesicoureteral Reflux
Pediatric Conference
9/18/2006
Vesicoureteral Reflux (VUR)
• Definition
– Retrograde flow of urine from the bladder
through the incompetent UV valve
• Low-pressure reflux
– VUR that occurs during bladder filling
• High-pressure reflux
– VUR that occurs during micturition
– May occur during bladder filling, voiding or
both
Incidence
• Estimated at >10%
• Incidence of VUR in children with a UTI
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–
–
–
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Less than 1 year of age: 70%
4 years old:
25%
12 years old:
15%
Adult:
5.2%
Percent decrease likely due to spontaneous
resolution, resulting from bladder growth and
elongation of the ureteral tunnel
• 17.2% prevalence in children without UTI hx
Incidence
• Infants with antenatally detected VUR show a
male preponderance
• 85% of VUR detected later in life occurs in
females
• Males presenting with UTI are more likely to have
VUR
• Boys tend to present at younger age
– 25% during the first 3 months of life
– Often have more severe reflux
• During first few months of life, uncircumcised
males are 10x more likely to have a UTI.
Incidence
• As much as 80% of prenatally dx’d VUR
occurs in boys
• Usually high grade and bilateral in boys
• Caucasian 10x > African-American
– Grade and percent who resolve spontaneously
equal once diagnosed
Etiology - Primary VUR
• Congenital anomaly of the UVJ
• Deficiency of the longitudinal muscle of the
intravesical ureter results in an inadequate
valvular mechanism
• Length of the intramural ureter to ureteral
orifice diameter
– 5:1 normally
– Less than 5:1 ratio, reflux occurs
Etiology - Secondary VUR
• Bladder obstruction and increased pressure
• Anatomic causes
– Posterior Urethral Valves (50% have VUR)
• Most common anatomic cause
– Ureteroceles (can obstruct bladder neck)
Etiology - Secondary VUR
• Functional causes - more common in both sexes
– Neurogenic bladder
• Spina bifida, sacral agenesis
– Nonneurogenic neurogenic bladder
• Acquired due to abnormal voiding patterns in a
neurologically normal child
– Bladder instability
• Most common urodynamic abnormality
associated with VUR
International Classification
• Based upon contrast in the ureter & renal pelvis during VCUG
– Grade I:
– Grade II:
– Grade III:
– Grade IV:
– Grade V:
Ureter only
Ureter, pelvis, calyces, no dilation, normal
calyceal fornices
Mild or moderate dilation and/or tortuosity of the ureter,
and mild or moderate dilation of the pelvis, but no or
slight blunting of the fornices
Moderate dilation and/or tortuosity of the ureter and
mild dilation of renal pelvis and calyces; complete
obliteration of sharp angle of fornices but maintenance of
papillary impressions in majority of calyces, but no or
slight blunting of the fornices
Gross dilation and tortuosity of ureter; gross dilation of
renal pelvis and calyces; papillary impressions are no
longer visible in majority of calyces
Grade I- ureter only
Grade II-Ureter, pelvis, calyces, no dilation,
normal calyceal fornices
Grade III-Mild or moderate dilation and/or
tortuosity of the ureter, and mild or moderate dilation
of the pelvis, but no or slight blunting of the fornices
Grade IV- Moderate dilation and/or tortuosity of the
ureter and mild dilation of renal pelvis and calyces; complete
obliteration of sharp angle of fornices but maintenance of
papillary impressions in majority of calyces, but no or slight
blunting
Grade V- Gross dilation and tortuosity of ureter; gross
dilation of renal pelvis and calyces; papillary impressions
are no longer visible in majority of calyces
Grade I- ureter only
Grade II-Ureter, pelvis, calyces, no dilation,
normal calyceal fornices
Grade III-Mild or moderate dilation and/or
tortuosity of the ureter, and mild or moderate dilation
of the pelvis, but no or slight blunting of the fornices
Grade IV- Moderate dilation and/or tortuosity of the
ureter and mild dilation of renal pelvis and calyces; complete
obliteration of sharp angle of fornices but maintenance of
papillary impressions in majority of calyces, but no or slight
blunting
Grade V- Gross dilation and tortuosity of ureter; gross
dilation of renal pelvis and calyces; papillary impressions
are no longer visible in majority of calyces
VCUG and US in newborn
VCUG: Bilateral reflux
Demographics of Reflux
•
•
•
•
•
•
Grade I:
5-8%
Grade II:
35%
Grade III:
25-35%
Grade IV:
15-25%
Grade V:5%
50% of children with reflux will have
bilateral VUR
Secondary VUR
• Treatment of Secondary VUR often allows
spontaneous resolution
• Treatment goals are to decrease uninhibited
contractions and lower pressure
– Ditropan contributes to resolution and
downgrading of VUR in 62%
Secondary VUR
• Strong association between intravesical pressures >
40cm H20 and VUR in MM and NGB
– VUR resolved or decreased in 55% of patients if leak point
pressures < 40
• If significant PVR is present, bladder emptying is
necessary
– Normal children without NGB
• Double and timed voiding
• Relaxation techniques
• Biofeedback
– Intermittent catheterization with anticholinergics
• If medical management fails to decrease pressure,
urinary diversion or augmentation may be necessary
Presentation & Diagnostic
Evaluation
• Most VUR patients present with infection
– Newborn: Failure to thrive, lethargy
– Older children: Fever, dysuria, frequency, lethargy, GI
symptoms
• Urine Culture in any child with fever or malaise
– Bag: most common, least reliable (high false positive with
contamination from skin and rectum)
– Mid-stream urine: if toilet-trained
– Catheterization = preferred
– Suprapubic aspiration = most sensitive
Etiology of VUR - Lower UTI
• Bladder inflammation decreases compliance
– VUR occurs due to increased pressure and distortion of the
UVJ
• Gram negative endotoxins can cause ureteral atony
– Some delay VCUG until UTI resolved
• Avoid false positive
– Sometimes VUR occurs only with UTI
• Some perform while on antibiotics
• VUR seen in 30 - 50% of children with UTI
• 30% already have evidence of parenchymal scar
• Scarring can occur after 1 UTI
– Fever not always present
Diagnosis
• VCUG and Renal U/S performed in:
– Any child < 5 with documented UTI
– Any child with febrile UTI regardless of age
– Any boy with UTI unless sexually active
• If no anatomic abnormalities are found
– Reassurance that UTIs do not pose serious threat to
upper urinary tract
– Improve toilet hygiene
Cystography
• VCUG
– Important to evaluate presence of VUR during filling and
voiding
– Evaluate UVJ and urethra, post void, delayed images for
drainage
– Accuracy is improved by repeating several cycles of voiding
and filling
• Nuclear cystography
– Less anatomic detail than VCUG
– Helpful during follow-up
– Less radiation (100-fold less)
Nuclear Cystography
Grade 1,2, and 3 Reflux
Upper Tract Assessment
• Ultrasound
– Diagnostic study of choice in the initial evaluation of the
upper tracts
– Cannot rule out reflux
– Assesses bladder and kidneys
– Renal size
– Parenchymal thickness
– Presence of scars, hydro, renal or ureteral anomalies
– Recommended annually for patients medically managed for
VUR, to detect evidence of scarring
IVP
• Less commonly used
• Roughly measures function
• Assess presence of scars and parenchymal
thinning
Renal Scan
• DMSA used to assess for pyelonephritis and
cortical renal scars
– 98% specific 92% sensitive in detection of renal
scars
– Valuable when pyelonephritis is suspected but has
not been proved
DMSA Scan: scarring in right kidney
Cystoscopy
• Limited role in diagnosis of VUR
• Orifice configuration does not predict VUR
• Indications for cystoscopy
– Nonvisualization of entire urethra on cystogram
– Uncertain about ureteral location or anomaly
– Inconclusive radiographic definition of lower or upper tracts
– Localization of paraureteral diverticulum
• Performed in concert with planned surgical repair
– Identify location of ectopic ureter
– Paraureteral diverticulum
Post-Infectious Scarring
• VUR predisposes the kidney to ascending UTI
– Pyelonephritis often occurs without VUR
• Patient Age
– Risk of scarring greatest < 1 year
– Uncommon > 5 years
• “Big bang” - most severe renal injury occurs
with first infection
Consequences of Reflux
Nephropathy
• Hypertension
– Most common cause of severe hypertension in
children and young adults
– Renal scarring leads to ischemia and elevated renin
– Hypertension is related to degree of VUR and
severity of scarring
– More profound with bilateral involvement
– Resolution of VUR does not reverse predisposition
to hypertension if scarring is present
Consequences of Reflux
• Renal Growth
– infection is the most likely cause of altered growth
– reimplantation can accelerate growth - not to normal size
• Renal Failure
– Uncommon due to VUR alone < 1%
– Implications of recurrent pyelonephritis
• 15-25% of children with ESRD in earlier studies
• currently accounts for 2% ESRD cases
• Somatic Growth
– Children with VUR are small for age
– Surgical correction of VUR and medically-controlled VUR
can positively affect growth
Associated Anomalies
• UPJ Obstruction
– 5-25% will have VUR
– 0.8%-14% of VUR patients also have UPJ
– Can not base management on VCUG alone (obstructed renal
pelvis can cause over-grading of VUR)
– High grade VUR can kink the ureter leading to UPJ
– When renal scan shows obstruction, pyeloplasty rather than
reimplantation
• Correcting reflux risks amplifying obstruction - edema
• Improve outflow may increase VUR resolution
• Re-implantation may be necessary later
Associated Anomalies
• Ureteral Duplication
– VUR is the most common abnormality associated
with complete ureteral duplication
– VUR is increased with duplication
– Resolution of VUR appears to be the same as single
systems
– VUR more often in the lower pole ureter
• Weigert-Meyer rule
• Lateral and superior position with short submucosal
tunnel
Associated Anomalies
• Bladder Diverticulum
– Lateral and cephalad to the orifice
– Disrupts UVJ anatomy - VUR
– Small diverticulum
• Resolution similar to primary VUR
– Large diverticulum
• Less likely to resolve
Pregnancy and Reflux
• Pregnancy causes decreased bladder tone and physiologic
dilation of upper tracts with increased urine volume and
decreased flow.
• Predisposes to bacteruria with propensity for
pyelonephritis
• In women with h/o reflux, increased risk of infectionrelated complications
• Increased risk for HTN
• With renal scarring, increased risk of preeclampsia
Spontaneous Resolution
• Age- and VUR grade- dependent
• Elongation of submucosal tunnel
– Bladder and ureteral growth
• Change of bladder dynamics
– Larger capacity
– Lower intravesical pressure
Spontaneous Resolution
• Low Grade
– Grade I: 82% at 5 years
– Grade II:80% at 5 years
• Intermediate Grade – III: 50% at 5 yrs
• Grade IV: 25% at 5 yrs
• Grade V
– 12% resolution
• Grade III & IV management presents the most
controversy
Spontaneous Resolution
• Age at diagnosis
– Younger children are more likely to have VUR
– VUR is more likely to resolve in younger children
– Intervals of significant growth and beneficial
urodynamic change are most likely to effect change
– Resolution usually occurs within the first few years
after diagnosis
– Rarely resolves if continued reflux after 5 years
Management Decision Making
• Spontaneous resolution of VUR occurs in many
infants and children - rarely at puberty
• More severe grades are less likely to resolve
• Sterile reflux does not appear to cause
significant nephropathy
• Extended courses of prophylactic antibiotics are
well tolerated by children
• Anti-Reflux surgery is highly successful in
capable hands
– 95-99% success rate
Management Decision Making
• Medical management initially recommended
for prepubertal children with I, II, III
• This also may be true for Grade IV - esp. in
younger children with unilateral disease
• If no trend in improvement is seen in 2 - 3
years, surgery is recommended
• Grade V is unlikely to resolve and surgery is
recommended after infancy
– Observation may be reasonable if diagnosed
perinatally
Management Decision Making
• Surgery recommended in most girls with
persistent VUR
– Implications for future pregnancies
– Especially if recurrent infections or scars present
• Some discontinue antibiotics at puberty in girls
– Surgery if UTI occurs
• Prophylaxis can be stopped at puberty in boys
– Less likely to develop UTIs
Medical Management
• Amoxicillin/Ampicillin
– Birth - 6 wks
• Bactrim
– >6 wks
– Biliary system matured
• Macrodantin
– > 2 months
– Minimizes fecal resistance
• Intermittent treatment not effective
Medical Management
• Treat dysfunctional voiding
– timed voids/double voids
– constipation
• Yearly Radiologic Studies
– U/S and Nuclear Cystography
– D/C prophylaxis when Cystography shows no VUR
• Complete reevaluation if develop
pyelonephritis
Surgical Management:
Indications for Surgery
• Breakthrough UTIs on prophylactic antibiotics
• Noncompliance with medical management
• Severe VUR (Grade IV & V), especially with
pyelonephrotic changes (evidence of scarring)
• Failure of renal growth, new renal scars, or
deterioration of renal function on serial studies
• Persistent VUR in girls at puberty
• Reflux associated with congenital abnormalities at the
UVJ (e.g. bladder diverticulum)
Surgical Management
• Decreases the incidence of pyelonephritis
– 50% to 10%
• UTI’s may persist
– Bacteriuria in 40% of post-op patients
Surgical Management
• Creates valvular mechanism
– Ureteral compression with bladder filling and
contraction
– Sufficient length and muscular backing
– 5:1 length to diameter
Surgical Management
• Techniques--infravesical
– Leadbetter-Politano
• Supra hiatal
• Intravesical
• 97 - 99% success rate
– Cohen
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Cross-trigonal
Intravesical
Useful for correcting VUR in thickened small or neuropathic bladder
Procedure of choice with BN reconstruction
96 - 99% success rate
Downside is difficulty with catheterizing UO’s
– Glenn-Anderson: infrahiatal, intravesical; 97-98% success
– Gil-Vernet: infrahiatal; 94% success
Cohen Cross-trigonal Technique
Cohen Cross-trigonal Technique:
Bilateral Reimplantation
Glenn-Anderson technique
Gil-Vernet Technique
Surgical Management
– Lich-Gregoir
• Extravesical
• 90 - 98% success rate
• Advantages are
– Does not involve urinary contamination
– Less chance of bladder spasm/hematuria
– Less invasive, shorter hospital stay
• Disadvantages include potential for damage to
nerves, leading to urinary retention in 4-36% of
cases
Lich-Gregoir
Extravesical
Technique
Endoscopic Management
• Deflux (Detranomer microspheres with sodium
hyaluronan, a polysaccharide)
– 62-88% success for Grade III and IV reflux,
respectively in short term follow-up2
• Silicone Microimplants
– Migration and safety concerns exist
• Teflon
– Not widely used due to concerns regarding local and
distant migration
• Collagen
– Not approved in the US
2 Stenberg and Lackgren. J. Urol, 1995, 154: 800-803
Laparoscopic Management
• Advantages
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Smaller Incisions
Less Discomfort
Brief Hospitalization
Quicker convalescence
• Disadvantages
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Learning curve
Intraperitoneal vs. extraperitoneal
Instrumentation limited for pediatric use
Increased operative time
Increased cost with length of procedure and disposable
equipment
Post-Operative Care & Evaluation
• Renal U/S
– 6 weeks
• VCUG
– 3-6 months
• Periodic F/U
– 18 months, 3 years, 5 years
– check U/A, BP, U/S
Early Complications
• Reflux
– Contralateral or ipsilateral ureter
– Trigonal edema, bladder dysfunction
– Majority are low grade
• Obstruction
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–
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Edema, spasms, blood clots
Most are mild
Occur 1-2 weeks post-op - pain, N/V, rarely fever
Renal scan shows delay in excretion
Nephrostomy tubes or ureteral stents if symptoms
persist
Late Complications
• Reflux
– Short length to diameter ratio
– Weak muscular backing
– Failure to treat secondary causes of VUR
• CIC and anticholinergics
• Treatment of dysfunctional voiding
• Obstruction
– Complete obstruction
• Ischemia or hiatal angulation
– Intermittent obstruction
• Lateral placement of orifice obstructs with filling
Reflux: Conclusions
• Common
• Indications for correction continue to
change
• Natural history of VUR changing with
perinatal diagnosis
• High resolution rate, medical management
• Surgical interventions highly successful
• New methods of surgical treatment evolving