# Treatment of Vesicoureteral Reflux after Puberty

Authors: J. Christopher Austin
Journal: Advances in Urology
 (2008)

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## Abstract

Vesicoureteral reflux is uncommonly diagnosed and treated after puberty. The natural history of uncorrected VUR after puberty is not documented. Postpubertal patients with recurrent pyelonephritis and VUR should be considered for treatment. Ureteral reimplantation, endoscopic injections, and laparoscopic or robotic ureteral reimplantation may be utilized. Endoscopic injection is an appealing option for these patients. The role of laparoscopic or robotic ureteral reimplantation in these patients is evolving.


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## Body

## 1. Introduction

Vesicoureteral reflux (VUR) is a common finding in children with urinary
tract infections (UTIs). The incidence
of VUR associated with UTIs drops significantly in older children, particularly
after the age of 5 [1]. It has been a long-held dogma of pediatric urology that
unresolved VUR should be treated before a child progresses through
puberty. There is concern that females
with uncorrected VUR will have problems with pyelonephritis when they become
sexually active and during pregnancy. Pyelonephritis
during pregnancy increases the risks of the pregnancy and possibly to the
unborn child as well. If these children
have their reflux corrected before they go through puberty, these problems
could be prevented. While in theory this justifies the surgical correction of
all children who fail to resolve their reflux during a period of observation,
there is little evidence to support treating all children and no long-term
studies documenting the natural history of uncorrected VUR after puberty. This manuscript will review the association
of VUR and UTIs in patients treated after puberty and examine the role,
nuances, and outcomes of treating VUR after puberty.


## 2. Clinical Importance of VUR after Puberty

There has been a long-standing observation of the association of febrile UTIs and the
development of renal scarring [2]. The riskiest time for the development of
renal scarring due to febrile UTI associated with primary VUR is infancy and
the risk of developing new scars drops significantly after age of 5 [3]. It is
still common to follow and treat patients beyond this age. While severe
scarring may predispose to chronic kidney disease in a small percentage
(estimated at 2%), the majority of children with VUR are not at significant
risk for renal failure [4]. There is a higher incidence of hypertension in
patients with renal scarring, but severe complications due to VUR are
unusual. The only reliable benefit to
patients who's VUR is surgically corrected is a decreased risk of
pyelonephritis, but the incidence of UTIs is similar to those who reflux has
persisted. These findings have led some
to consider stopping antibiotic prophylaxis in selected children and ceasing surveillance for resolution [5, 6].
Voiding cystourethrograms (VCUG) can be perceived as traumatic by children and
simplifying their follow-up and avoiding these tests may be a major factor in
discontinuing follow-up for some parents. As a result of these practices more and more physicians are going to
allow children with persistent VUR to continue through puberty with uncorrected
VUR. As a group, these patients will
likely have lower grades of VUR, infrequent UTIs, and normal renal function.
There are currently no longitudinal studies documenting just what risks these
patients will face and whether their VUR will be a significant problem during
adolescences and adulthood. It is likely that some of these patients will have
future problems with UTIs and be considered for treatment of their VUR after
puberty.There has also been a change in VUR management by some pediatric urologists that is the
polar opposite of stopping prophylaxis and observing patients. Instead of
following patients for resolution of their VUR, primary therapy with endoscopic
injections after the diagnosis of VUR is being offered [7]. Touted as a
minimally invasive alternative, the “15-minute cure” is being used as upfront
therapy in patients after diagnosis to avoid the need to prolonged antibiotic
prophylaxis and prolonged follow-up while waiting for the VUR to resolve. While success rates greater than 90% are
reported by experienced surgeons, the follow-up in these series is generally
short with VCUGs being performed usually within 3 months of the procedure [8]. There is a known rate of relapse for this
method which is highest for collagen, and was reported to be greater than 50%
at 5 years [9]. The relapse rate is lower for other agents [10, 11]. If there
is a 10–15% relapse over 5–10 years (a
reasonable estimate given the few long-term studies available) it is likely that
there will be increasing numbers of late failures of endoscopic therapy. Of
these patients, some will present after puberty with pyelonephritis and
recurrent VUR.


## 3. VUR and UTIs after Puberty

The primary motivation for treatment
of VUR before puberty has been over concerns of increased risk of UTIs when
female patients become sexually active or pregnant. To my knowledge, however, the natural history
of women with persistent VUR during pregnancy has not been documented. Pyelonephritis is a known risk to pregnant
women and strongly associated with bacteruria. Large series have reported rates of 2% of pregnant women [12]. In
pregnant women with a history of VUR or surgically corrected VUR, higher rates
of UTIs and pyelonephritis have been reported. Mansfield et al.
reported complications during pregnancy for patients who had undergone surgical
correction of VUR and a group with a history of VUR that did not undergo
surgery [13]. The rate of cystitis and
pyelonephritis was 22% and 18%, respectively, during pregnancy for the patients
with surgically corrected VUR. These rates were higher than the patients
without treatment of their VUR with cystitis in 15% and pyelonephritis in
1.5%. They also reported a high rate of
UTIs with the onset of sexual activity in 75% of patients with surgically
treated VUR and 62% of those with a history of VUR that was not treated. There is a significantly increased risk of
UTIs in women with a history of VUR. There could be multiple explanations for the differences in the two
groups including that the surgical procedure is the cause of the increased
UTIs. Due to the retrospective nature however, the authors point out that this
observation of higher rates of UTIs in the surgically treated patients does not
prove that the problem is due to the surgery. Other factors may be responsible for these differences, such as
selection bias. These patients likely had an increased susceptibility to UTIs,
which is likely what pushed them to surgical correction in the first place. The authors recommend that pregnant women with a history of ureteral reimplantation surgery undergo frequent screening for bacteruria during pregnancy and that prophylactic antibiotics be considered in these patients. Other series of long-term follow-up of patients with VUR treated with ureteral reimplantation surgery have similar findings. Beetz et al. reported a 25-year follow up in 158 patients [14]. Female patients reported subsequent UTIs in 74% after surgery versus 10% of males. 17% developed UTIs during pregnancy, however, they did not report whether these
patients had pyelonephritis or cystitis. Of the UTIs, most (66%) were afebrile
versus preoperatively where the UTIs were febrile. It remains unknown as to
whether patients experiencing continued problems with UTIs after surgery would
have fewer problems if they had not undergone surgery.


## 4. Which Patients Should Be Evaluated and Treated?

The incidence of VUR after puberty
is significantly lower than in young infants with febrile UTIs [1]. It has been
well established that VUR is a risk factor for pyelonephritis and that it
frequently is present as one of several risk factors for UTIs. Voiding dysfunction must always be considered
in this patient population and treated appropriately. With proper treatment and
modification of risk factors such as infrequent voiding, dysfunctional voiding,
constipation, and incomplete emptying the VUR may be eliminated without
surgical treatment [15].Most postpubertal patients with VUR will present with UTIs. Since the majority of patients will not have
VUR and assuming that VUR is an important risk factor for pyelonephritis, what
are the factors that should prompt an evaluation for VUR in a postpubertal
patient? First and foremost should be a history of recurrent febrile urinary
tract infections, as these patients if found to have reflux, have a good chance
of having their symptoms alleviated if VUR is found and treated. Suspicion
should be raised if there is a history of prior VUR, febrile infections as a
young child, or a family history of VUR. Due to the high association of renal scarring and VUR, patients who have
a history of recurrent febrile UTIs and evidence of renal scarring on imaging
studies should be evaluated for VUR. To evaluate for VUR a standard VUCG may be
performed, or if there are symptoms worrisome for voiding dysfunction a
videourodynamics study. In patients with evidence of renal scarring or a small
kidney on ultrasound, a DMSA renal scan should be obtained to evaluate for
renal scarring and the differential function. Typically, the grade of VUR is an important factor for predicting
resolution and risk of renal scarring; however, in postpubertal patients it has
not been studied as extensively. It is expected that the rates of spontaneous
resolution will be lower after puberty.


## 5. Surgical Treatment of VUR after Puberty

One of the more humbling experiences for a pediatric urologist is their first ureteral
reimplantation done on a female after puberty. These difficulties start as
females approach puberty. During puberty, the pelvis widens and deepens in the
female. The trigone assumes a deeper retropubic location which makes access to
the ureteral orifices and the mobilization of the ureters more difficult.
Additionally, the plexus of vein running across the surface of the bladder enlarge and are more prone
to troublesome bleeding during ureteral dissection. Though not well documented,
most pediatric urologists would agree that, if a child truly needed ureteral
reimplantation for correction of their VUR, then the operation is best
performed if they are operated on during childhood rather than after puberty.
Experience would tell us that they recover quicker and that technically the
surgery should be more successful, however, there are not series documenting
poorer results after ureteral reimplantation for patients treated after
puberty. Options for treatment of VUR in
patients after puberty include intra- or extra-vesical ureteral reimplantation,
endoscopic injection, and laparoscopic or robotic reimplantation. In patients with unilateral VUR to a poorly
functioning kidney nephrectomy may be an alternative choice to ureteral
reimplantation. This can be performed laparoscopically with rapid recovery and
short hospitalization.


## 6. Ureteral Reimplantation

As mentioned previously, the postpubertal changes in women make the surgical access to the
trigone more challenging and limit exposure; however, ureteral reimplantation
can be performed in women successfully. In males, the changes are less dramatic. Published results of ureteral reimplantation in postpubertal patients
are sparse due to the limited number of patients in whom this surgery is
indicated. From a technical standpoint,
it is prudent to position the patient over the break in the OR table. This allows
the table to be flexed if necessary to open the pelvis and improve retropubic
exposure. This is similar to the
positioning of a male undergoing radical retropubic prostatectomy. The size and body mass index will play a role
with obese patients creating more difficulties with exposure. Proper surgical
planning and the use of larger and more flexible fixed retractors such as a
Bookwalter rather than the Denis-Browne retractor will facilitate the
procedure. Both ureteral advancements and ureteroneocystotomy procedures (e.g.,
Cohen, Glenn-Anderson, and Politano-Leadbetter) can be performed but limited
data is available on their use in the treatment of VUR postpuberty [16–20]. There have
been reports of the use of trigonoplasty (Gil-Vernet) procedures, which in
postpubertal patients offer the advantage of less dissection and mobilization [21, 22].
Success rates of up to 97% have been reported but follow-up is limited to only
11 months.


## 7. Endoscopic Injection

Although controversy remains about the role of endoscopic injection for VUR as an
alternative to ureteral reimplantation in young children, there are few
“reimplanters” who would completely dismiss this option in patients after
puberty. This technique has been practiced for over 20 years and a variety of bulking
agents have been injected including polytetrafluoroethylene paste,
gluteraldehyde cross-linked bovine collagen, polydimethysiloxane, and detranomer/hyaluronic acid copolymer (D/HA) [23]. In the United
States the D/HA copolymer is the only agent that has been FDA approved for use
in children. A recent series by Okeke et
al. reported 9 women (mean age of 26) with symptomatic VUR associated
with acute pyelonephritis who were treated endoscopically with D/HA [24]. All
were treated successfully with no reflux by VCUGs at 3 months postoperatively,
although 1 did require a second injection for persistent VUR. Two patients had
transient flank pain immediately postoperatively which resolved after a few
days. At a mean follow-up of 14 months, none of the patients had further
infections or symptoms. In children, the treatment of VUR with D/HA injections
has been associated with a lower incidence of UTIs postoperatively [25]. It is
unknown whether or not postpubertal patients are at the same risk for late
failures of endoscopic injection as was described in some of the original
series of children.


## 8. Laparoscopic and Robotic Ureteral Reimplantation

Minimally invasive ureteral reimplantation for VUR has been performed for over a decade;
however its widespread uses have been slow to spread. Proponents of
laparoscopic surgery would cite the limited laparoscopic experience of most
pediatric urologists as a primary factor for this slow adaptation. However,
many would argue against relearning to do a procedure which has rapid recovery,
high success rate, low complication rate, and is done through an inconspicuous
incision. A low, transverse abdominal incision leaves a scar that often blends
into the natural creases of the abdominal skin leaving a barely visible mark. If
placed low enough it is covered by undergarments and is not disfiguring. Given
the questionable benefits and technical difficulties the laparoscopic technique
has been slow to gain acceptance. One
population where this approach actually may be a real asset is in treating VUR
after puberty.Both intra- and extra-vesical laparoscopic techniques for reimplantation have been described in children [26–28]. In the
postpubertal female, the advantage for laparoscopy is that the scope and
instruments can reach deep into the pelvis with good visualization. Shu et
al. reported a series of laparoscopic extravesical reimplantations
performed for VUR in postpubertal females at a mean age of 18 [29]. One patient
underwent bilateral and the other 5 unilateral reimplantation. 1 patient had
transient ureteral obstruction requiring a temporary stent placement. All had
resolution of their VUR postoperatively.Robotic assisted laparoscopic surgery has become a widely practiced urologic technique
for performing radical prostatectomy [30]. The surgeons utilizing the robot for
prostatectomies tout the increased magnification, 3D visualization, and
precision movements the wristed instruments as advantages over the open
surgical procedure. The neurovascular
bundles are well visualized, as is the apical dissection of the prostate and
urethra. Performing deep pelvic surgery such as ureteral reimplantation in
postpubertal patients is a situation where the robotic approach may have an
advantage over traditional open surgical reimplantation. There are limited
reports of robotic ureteral reimplantations being performed in children [31].
The robot allows a surgeon with good open surgical skills to perform complex
laparoscopic procedures. Extravesical ureteral reimplantation has been associated
with postoperative urinary retention when performed bilaterally [32]. This is felt to be due to injury to the pelvic
plexus during the dissection of the ureter extravesically [33]. Casale et
al. reported a series of 41 children with a mean age of 33 months
treated with bilateral robotic “nerve-sparing” extravesical reimplantation [34]. All children voided well after catheter
removal on postoperative day number 1. No patient had retention as documented
by ultrasonic bladder scanning. Reflux was cured in 97% and no ureters were
obstructed. If these impressive results can be achieved by other surgeons and
applied to postpubertal patients, this could become the preferred approach to ureteral
reimplantation surgery after puberty.


## 9. Conclusions

The natural history of untreated VUR
in postpubertal patients is unknown. Treatment of VUR should be considered in those patients with VUR and
recurrent febrile UTIs. The optimal method to treat VUR is not clear.
Endoscopic injection is a minimally invasive approach which has a good success
rate for treating VUR and offers some benefits over ureteral reimplantation.
The role of laparoscopic and robotic ureteral reimplantation is evolving and
may offer some advantages over open ureteral reimplantation in postpubertal
patients.



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