Editing Pediatrics: Vesicoureteral Reflux (section)

=== 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