Editing Pediatrics: Vesicoureteral Reflux (section)

== Management ==

* '''See [[AUA: Vesicoureteral Reflux (2017)|2017 AUA Guidelines on Vesicoureteral Reflux]]'''

=== Principles of Reflux Management ===
# '''BBD is by far one of the most critical and modifiable variables that affect VUR management and attendant UTIs'''
#* '''Constipation must be recognized and eliminated as much as possible to establish optimal conditions for successful spontaneous or surgical resolution of reflux'''
#* BBD lowers VUR resolution rates.
# '''Parental perceptions of reflux management must be considered when treating a child with reflux'''
# '''Spontaneous resolution of reflux is very common'''
#* ≈80% of low-grade and ≈50% of grade 3 reflux will resolve spontaneously.
# '''High-grade reflux is less likely to resolve spontaneously'''
# '''Sterile reflux is benign'''
# "Extended use of prophylactic antibiotics is benign"
# Success of (open) surgical correction is very high
#* Ureteral reimplant is successful in correcting reflux in > 98% of cases

=== Options: ===
* '''Includes management of any bowel-bladder dysfunction'''
* '''First-line (classic approach): watchful waiting''' '''with''' '''daily low-dose antibiotic prophylaxis'''
* '''Second-line: intervention'''
** '''Options:'''
*** '''Endoscopic'''
*** '''Open/laparoscopic ureteral reimplant'''
** '''Failure to address voiding abnormalities can adversely affect outcome of anti-reflux surgery'''

=== Watchful waiting with daily low-dose antibiotic prophylaxis ===
* '''Underlying principle: every case of reflux should be offered time to resolve spontaneously, despite grade'''
* Maintaining urine sterility (through both prophylactic antibiotics and strict attention to bladder and bowel management) is the cornerstone of watchful waiting medical management
* '''Nighttime dosing allows for antibiotic concentration in the bladder urine over the longest period of expected physiologic retention, when infection is most likely to develop.'''
* '''For children age < 2 months, the most commonly used medications are trimethoprim and amoxicillin.'''
* '''In newborn patients, it is reasonable to wait until ≈5 years of age assuming no intercurrent breakthrough infections occur'''. Beyond this age, it is commonly believed that the kidneys become less prone to scarring after pyelonephritis. Thus, some withdraw prophylaxis as the child approaches the age of 5.
** '''After this age, boys with asymptomatic reflux will require little or no formal follow-up''' as long as lifelong attention to good bladder habits is reinforced, and they are counseled to seek prompt medical attention if a pyelonephritis were to occur in the future, as well as reassessment of their reflux status. 
*** Uncircumcised male children older than 1 year do not appear to be at higher risk for development of recurrent UTI after discontinuation of CAP.
** '''Girls have traditionally undergone open surgical correction, even for asymptomatic reflux that fails to resolve by the age of 5, on the premise that it will reduce maternal and fetal morbidity during a future pregnancy'''
*** '''Women with a history of VUR have increased morbidity during pregnancy because of infection-related complications, whether the reflux has been corrected or not.'''
**** '''Addintional risk factors that may lead to increased morbidity in pregnant patients with VUR:'''
****# '''Hypertension'''
****# '''Renal insufficiency'''
****#* Associated with increased risk for fetal demise and accelerated maternal renal disease
****# '''Renal scarring'''
****#* Associated with an increased incidence of hypertension, increased risk for preeclampsia, increased risk of developing acute pyelonephritis, and a higher rate of obstetric interventions
****# '''History of prior infections'''
****#* Associated with increased risk of bacteriuria during pregnancy
**** '''Persistent VUR is associated with increased risk of developing acute pyelonephritis'''
**** VUR with normal kidneys is associated with an increased risk for hypertension during the last trimester
**** Impaired renal function is
**** '''Most clinicians recommend surgical correction for females with reflux that persists beyond puberty to minimize maternal and fetal morbidity'''
* '''In patients diagnosed after one or more episodes of pyelonephritis, the presence of scarring on renal scintigraphy may temper a decision for extended prophylaxis and observation''', particularly if:
** Scarring is extensive
** Reflux is high grade
** Renal function is already globally depressed
** Congenital dysmorphism of one or both kidneys is present
* '''Breakthrough febrile UTIs or pyelonephritis while on antibiotic prophylaxis are generally considered an indication for termination of watchful waiting and correcting the reflux.''' Anxiety related to ongoing reflux also warrants strong consideration for reflux correction
** '''BBD is associated with higher breakthrough infection rates.'''
* '''Adult patients who present with non-obstructive flank pain, febrile UTIs, or pyelonephritis and are found to have VUR have traditionally been offered antireflux surgery'''
* '''Cystoscopy'''
** '''Cystoscopy in the course of conservative management of VUR is indicated only to confirm or manage abnormalities found on other imaging modalities'''
* '''Landmark Studies'''
** '''International Reflux Study in Children'''
*** '''Population: 306 children aged < 11 years with high-grade reflux from North America and Europe'''
*** '''Randomized to watchful waiting with antibiotic prophylaxis vs. corrective open surgery'''
*** '''Primary end points: new renal scars and renal growth'''
*** '''Results:'''
**** '''No siginificant difference in risk of new renal scars'''
***** '''Antibiotic prophylaxis and surgery equally effective in reducing, but not eliminating, new scar formation'''
**** '''Surgery more effective than antibiotic prophylaxis in reducing, but not eliminating, the risk of pyelonephritis'''
**** '''Nosiginificant difference in risk of incident UTI (38%)'''
*** Jodal, Ulf, et al."Ten-year results of randomized treatment of children with severe vesicoureteral reflux. Final report of the International Reflux Study in Children." ''Pediatric Nephrology'' 21.6 (2006): 785.
** '''RIVUR'''
*** '''Population: 607 children with''' dilated and non-dilated '''VUR that was diagnosed after''' a first or second '''febrile or symptomatic UTI'''
**** Population was overwhelmingly female (91%)
**** Half of the study participants were < 11 months of age
*** '''Randomized to trimethoprim-sulfamethoxazole prophylaxis vs. placebo'''
*** '''Primary outcome: recurrence of UTI'''
*** '''Results:'''
**** '''45% significant decrease in UTI recurrence with antibiotic prophylaxis''' (RR: 0.55; 95% CI: 0.38-0.78)
***** When stratified into dilated and non-dilated groups, children with dilated VUR were more likely to have symptomatic recurrences than those with non-dilated VUR
***** Prophylaxis was particularly effective in children whose index infection was febrile and in those with baseline BBD.
**** '''No difference in the occurrence of renal scarring'''
**** '''Adverse reactions to antibiotics were reported in 2% of both the antibiotic prophylaxis and placebo groups.'''
*** '''Criticisms:'''
**** '''Population may not reflect typical patient in practice'''
***** '''Majority female and half under age 11 months'''
***** '''Trial does not address patients with VUR and no history of UTI'''
*** '''RIVUR Trial Investigators. Antimicrobial prophylaxis for children with vesicoureteral reflux. NEJM 2014; 370: 2367.''' <nowiki>https://www.nejm.org/doi/full/10.1056/NEJMoa1401811</nowiki>
* '''Antibiotic Controversies and Potential New Approaches'''
** There was a belief that the ''first'' febrile UTI, in the presence of reflux, will create the greater proportion of clinically significant post-infection scarring, This belief, in turn, spawned the now routine and widespread US follow-up of prenatal hydronephrosis for evidence of postnatal hydronephrosis, which, if present, then triggers the documentation of reflux by cystography to prevent the first febrile UTI by instituting immediate antibiotic prophylaxis if reflux is found.
** Antibiotic prophylaxis is destined to fail without adequate teaching and periodic review of perineal hygiene techniques, timely bladder emptying habits, and anticonstipation measures
** Prophylactic antibiotics are more likely to benefit patients with:
*** Higher grade reflux
*** Baseline bladder dysfunction
*** Bowel and bladder dysfunction
*** Febrile UTI

=== Endoscopic ===
* '''A reasonable alternative for children being considered for surgical correction'''
* '''Success rates vary across centers and that outcomes may not be durable.'''
** Higher success rates associated with:
**# Volume of Dx/HA used
**# Surgeon experience
**# Volcano-shaped mound with no hydrodistention
**# Utilization of the double hydrodistention-implantation technique
**# Accurate needle entry point during endoscopic injection, as well as the needle placement
*** Negative intraoperative cystogram is not associated with endoscopic success rates
* '''Untreated BBD is associated with decreased resolution rates of VUR at initial follow-up in children treated with endoscopic surgery'''
* The learning curve for endoscopic injection is believed to be different from that of open surgical reimplantation, but studies have compared these two approaches
* Indications for treatment are the same as that of open surgical reimplantation
* '''Materials used for endoscopic correction of reflux'''
** Characteristics of an ideal injectable biomaterial (4):
**# Non-toxic and stable without migration to vital organs
**# Cause minimal local inflammation, while at the same time be well encapsulated by normal fibrous tissue and fibrocytes
**# Easy to inject through a long needle that passes easily through most standard endoscopic instruments
**# Viscous enough to prevent leakage from the puncture site and maintain its injected volume and the mound shape after the normal process of exchange and excretion of any carrier molecules.
** '''Classified as particulate vs. degradable and autologous vs. non-autologous'''
*** '''Disadvantage of particulate agents is risk of migration'''
*** '''Disadvantage of degradable agents is less durability'''
**** '''Deflux is biodegradable, the carrier gel is reabsorbed''', and the dextranomer microspheres become capsulated by fibroblast migration and collagen ingrowth
**** '''DX/HA loses ≈23% of its volume beyond 3 months of follow-up'''
*** '''Autologous Materials'''
**** '''Fat, collagen, muscle, and chondrocytes have been evaluated as bulking agents'''
* '''Follow-Up after Endoscopic Treatment'''
** '''The child is maintained on antibiotics for 3 months.'''
** '''US and VCUG are obtained at 3 months.'''
*** '''If reflux is persistent, a repeat injection can be considered 6 months after the initial injection'''
*** '''If there is still no resolution, open surgery is recommended.'''
**** '''Most reports to date have not indicated any additional difficulty with open surgery after endoscopic correction using Deflux'''

=== Ureteral reimplant ===
* '''The principles of ureteral reimiplant for reflux include the following:'''
*# '''Exclusion of causes of secondary VUR'''
*# Adequate mobilization of the distal ureter without tension or damage to its delicate blood supply
*# '''Creation of a submucosal tunnel that is generous in caliber and satisfies the 5:1 ratio of length to width'''
*# Attention to the entry point of the ureter into the bladder (hiatus), the direction of the submucosal tunnel, and the ureteromucosal anastomosis to prevent stenosis, angulation, or twisting of the ureter
*# '''Attention to the muscular backing of the ureter to achieve an effective anti-reflux mechanism'''
*# Gentle handling of the bladder to reduce postoperative hematuria and bladder spasms
** '''Common to each type of open surgical repair for reflux is the creation of a valvular mechanism that enables ureteral compression with bladder filling and contraction, thus reenacting normal anatomy and function.'''
* '''Ureteral duplication'''
** Approximately 10% of children undergoing antireflux surgery have an element of ureteral duplication. The most common configuration is a complete duplication that results in two separate orifices. This is best managed by preserving a cuff of bladder mucosa that encompasses both orifices. Because the pair typically share blood supply along their adjoining wall, mobilization as one unit with a “common sheath” preserves vascularity and minimizes trauma.
* '''Success rate for ureteroneocystostomy in patients with low-grade primary VUR approaches 100%'''
** '''BBD does not alter surgical resolution rates in children treated with open surgery'''
** '''BBD is associated with increased incidence of UTI after surgery.'''
* '''Follow-Up after Ureteral Reimplant'''
** '''An US is necessary at 6-12 weeks postoperatively'''
*** Ureteral obstruction can be clinically silent, and therefore, the absence of ureteral obstruction must be documented.
*** '''Minimal ureteral dilation and low-grade hydronephrosis on early post-operative ultrasonography is not unusual'''
**** '''Persistence of this dilation > 3 months or its progression should be further investigated'''
** '''Postoperative VCUG can be avoided in patients with:'''
**# '''Low-grade primary reflux initially'''
**# '''Normal preoperative and post-operative US examinations'''
*** Recall that follow-up after endoscopic management includes post-operative antbiotics for 3 months and imaging with US and VCUG
** Children with renal scarring should have their blood pressure measured at every visit with their family physician
* '''Complications of Ureteral Reimplantation'''
** '''Early Complications'''
*** '''Persistent Reflux'''
**** '''Early reflux after ureteroneocystostomy usually is not a significant clinical problem and commonly resolves by 1 year on repeat cystography'''
*** '''De novo contralateral Reflux'''
**** '''Prophylactic bilateral reimplantation for unilateral reflux, to avoid contralateral reflux, is not warranted on the basis of the high spontaneous resolution rates'''
*** '''Obstruction at the anastamosis'''
**** Early after surgery, various degrees of obstruction can be expected of the reimplanted ureter. Edema, subtrigonal bleeding, and bladder spasms all possibly contribute. Mucus plugs and blood clots are other causes.
**** '''Most postoperative obstructions are mild and asymptomatic and resolve spontaneously without requiring additional surgery.''' More significant obstructions are usually symptomatic.
***** Affected children typically present 1 to 2 weeks after surgery with acute abdominal pain, nausea, and vomiting
***** '''In the more significant cases, drainage of the system either by retrograde insertion of a double-J stent or a percutaneous nephrostomy tube may be necessary'''
**** '''Many of these cases resolve without requiring additional surgery'''
** '''Late complications'''
*** '''Obstruction at the anastamosis'''
*** '''Recurrent or Persistent Reflux'''
**** '''Causes (4):'''
****# '''High-grade reflux'''
****# '''Inadequate ratio of tunnel length to ureteral diameter'''
****#* Development of a short tunnel and failure to taper the excessively wide ureter are important factors
****# '''Failure to recognize secondary reflux''', especially associated with neurogenic bladders and PUV bladders.
****# '''Bladder and bowel function''' preoperatively, as well as in all cases of persistent or recurrent reflux.
* '''Laparoscopic approach'''
** Should theoretically provide the success rate and durability of open surgery while avoiding its morbidity.
** Procedures have been attempted laparoscopically (3)
**# Extravesical reimplant
**# Gil-Vernet procedure
**# Cohen cross-trigonal reimplant.