Management of vesicoureteral reflux in children

INTRODUCTION — 

Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder into the ureter and kidney. Historically, management was based on the premise that VUR predisposes patients to acute pyelonephritis by transporting bacteria from the bladder to the kidney, which may lead to kidney scarring, hypertension, and end-stage kidney disease. Some aspects of this long-held belief have been increasingly questioned. As a result, there is controversy regarding the optimal management of patients with VUR and management has become more individualized and is often conservative for children with milder VUR.

The management of VUR will be reviewed here. Most of these children are initially diagnosed with VUR after they present with a urinary tract infection (UTI); others are identified during an evaluation for hydronephrosis or congenital anomaly of the kidney and urinary tract (CAKUT) or, less commonly, testing of asymptomatic siblings. The presentation, diagnosis, and clinical course of VUR are discussed elsewhere. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

GOALS — 

The goals of VUR management are to:

●Prevent recurrent febrile urinary tract infections (UTIs)

●Prevent kidney damage (eg, kidney scarring) and negative impact on kidney function

●Minimize the burden of treatment and follow-up

●Identify and treat children with bladder and bowel dysfunction (BBD)

ADDRESS ASSOCIATED RISK FACTORS

Bladder and bowel dysfunction — Bladder and bowel dysfunction (BBD) is a common finding in children (especially in girls) during and after toilet training (and possibly before) and may be associated with VUR [1-5]. Patients with both BBD and VUR have a higher incidence of breakthrough urinary tract infection (UTI; any UTI while on prophylactic antibiotic therapy), longer time for VUR resolution, and increased failure rate of endoscopic correction compared with patients with only VUR [1-3,6-8]. Thus, it is important to identify and treat BBD in any patient with VUR.

Symptoms of BBD include urinary symptoms (urinary incontinence, urinary urgency/frequency, infrequent voiding, recurrent UTI, and dysuria), as well as symptoms of abdominal pain, constipation, and fecal soiling. (See "Etiology and clinical features of bladder dysfunction in children" and "Evaluation and diagnosis of bladder dysfunction in children".)

Treatment of BBD improves bladder function and promotes VUR resolution, including some patients with grade V reflux [9,10]. Interventions include laxatives and stool-bulking agents, timed frequent voiding, pelvic floor exercises, behavioral modification, and, in some cases, anticholinergic therapy. (See "Management of bladder dysfunction in children".)

Uncircumcised males — For uncircumcised infant males, particularly those with a high-grade VUR, we offer treatment for physiologic phimosis with topical corticosteroid therapy or circumcision to reduce the risk of UTI. (See "Neonatal circumcision: Risks and benefits", section on 'Reduction in urinary tract infection' and "Care and complications of the uncircumcised penis in infants and children", section on 'Management of physiologic phimosis'.)

APPROACH BASED ON VESICOURETERAL REFLUX SEVERITY — 

Therapeutic choices to manage VUR include active surveillance (watchful waiting), antibiotic prophylaxis, and surgical correction. (See 'Therapeutic options' below.)

Consistent with consensus guidelines [8], our management approach is based, in part, on severity of VUR (figure 1) because more severe VUR is associated with increased risk of febrile urinary tract infection (UTI) and kidney scarring and decreased likelihood of spontaneous resolution. Additional individual factors that contribute to management decisions include the presence of bladder and bowel dysfunction (BBD; in toilet-trained children), risk factors for chronic kidney disease (eg, kidney scarring from congenital dysplasia or recurrent pyelonephritis), and parent/caregiver preferences regarding choice of intervention and burden of adhering to therapy and follow-up, as outlined in the following sections.

Grades I and II — Children with grades I or II reflux can be managed with either surveillance or antibiotic prophylaxis. These children are generally at low risk for pyelonephritis and kidney scarring and are very likely to have spontaneous resolution of their VUR. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

Accordingly, we provide the family/caregivers with information to help them choose between the following treatment options (algorithm 1):

●Surveillance – The surveillance approach (watchful waiting without prophylactic antibiotics) is a reasonable option if the family is able and willing to promptly seek care in case of fever or other signs/symptoms of UTI and commits to long-term follow-up. This approach may be more appropriate in toilet-trained, verbal children who can communicate their symptoms but also can be considered in the preverbal infant or child. When offering this option, we emphasize the need for prompt recognition and treatment of any subsequent urinary infection. Additional infections would trigger discussion of either antibiotic prophylaxis or surgical management. (See 'Surveillance' below.)

Surveillance is also an appropriate option for infants and young children with low-grade VUR who have no history of UTI [8]. These children may come to attention during an evaluation for prenatally diagnosed hydronephrosis. In some cases, the VUR is identified in an asymptomatic child who was evaluated because their sibling has VUR (however, routine screening for VUR is not recommended for asymptomatic siblings).

●Antibiotic prophylaxis – We suggest antibiotic prophylaxis for children with low-grade reflux and any of the following:

•History of recurrent UTI

•BBD (because of increased risk for infection)

•Unable to adhere to the requirements of surveillance therapy, including presenting promptly for evaluation of fever or other symptoms of possible UTI

•Kidney scarring (eg, on a dimercaptosuccinic acid [DMSA] renal scan, if performed)

•Congenital anomalies of the kidney and urinary tract (CAKUT), such as a solitary kidney

In addition, antibiotic prophylaxis may be preferred for infants or younger nontoilet-trained children; the surveillance approach is more difficult for this age group because they are often unable to communicate symptoms of an infection. (See 'Antibiotic prophylaxis' below.)

For either of these strategies, we also address any associated BBD and offer counseling to reduce the risk of UTIs in uncircumcised males. (See 'Address associated risk factors' above.)

We do not suggest surgical correction as initial therapy for patients with grades I or II VUR, because there is a high likelihood of spontaneous resolution and a low risk of kidney scarring with medical management; the long-term risk of kidney scarring is similar with medical and surgical management. If the family/caregiver desires, we discuss the success rate, risks, and costs of surgical correction. Surgical correction remains an alternative for those who are not comfortable with either surveillance or continuous prophylaxis. Furthermore, surgical intervention is indicated for patients with persistent low-grade VUR who have one or more breakthrough infections on antibiotic prophylaxis or those who develop new kidney scarring or acute kidney injury. (See 'Surgical treatment' below.)

Grades III to V — For children with grades III to V reflux (figure 1), initial management is focused on reducing the risk of febrile UTIs and treating BBD (if present). This conservative approach is appropriate because VUR often improves by two or three years of age and/or with management of BBD.

Our approach is as follows:

●Antibiotic prophylaxis – For most children with grades III to V reflux, we suggest initial management with antibiotic prophylaxis rather than surveillance (algorithm 2). For these children, antibiotic prophylaxis reduces the risk of febrile UTIs and may reduce the risk of kidney scarring and chronic kidney disease. A possible exception is children with grade III VUR that was diagnosed by screening, rather than after presenting with a UTI, provided that they have no associated CAKUT. For these children, it would be reasonable to choose observation rather than antibiotic prophylaxis because they may be at lower risk for UTI. (See 'Antibiotic prophylaxis' below.)

●Detection and treatment of BBD – For children who are toilet trained, we monitor for symptoms of BBD, with further evaluation if indicated. If BBD is diagnosed, we initiate measures to improve bladder and bowel function, with ongoing monitoring to see whether VUR spontaneously resolves or improves. A trial of therapeutic intervention for BBD should be provided before considering any surgical intervention for VUR. (See 'Bladder and bowel dysfunction' above and "Management of bladder dysfunction in children".)

●Circumcision – For male infants who are uncircumcised, we offer treatment for physiologic phimosis with topical corticosteroid therapy or circumcision to reduce the risk of UTI. (See 'Uncircumcised males' above.)

●Candidates for surgery – Surgery should be considered for children with any of the following characteristics and without other urologic abnormalities (eg, ureterocele) (see 'Surgical treatment' below):

•Grade IV or V reflux that persists in children beyond two or three years of age (despite appropriate management of BBD, if present)

•One or more breakthrough UTIs (defined as a UTI that occurs despite adherence to prophylaxis regimen)

•Significant side effects from continuous prophylactic antibiotics (see 'Complications' below)

•Family unwilling or unable to adhere to medical management (prophylactic antibiotics, seeking medical attention for fever or symptoms suggesting UTI, and long-term follow-up)

•New kidney scarring or other evidence of acute or chronic kidney injury

●Family/caregivers preference – For all of the above decisions, we discuss the benefits, risks, and treatment burden with the family/caregivers, followed by shared decision-making. The preference of the family/caregivers plays a major role in the final therapeutic decision.

THERAPEUTIC OPTIONS

Surveillance — Active surveillance (watchful waiting) consists of observation and prompt treatment of any episodes of urinary tract infection (UTI). Families must seek medical attention when there are symptoms suggestive of UTI or unexplained fever.

●Indications – In our practice, we offer surveillance as an option for:

•Children with low-grade VUR (grades I and II (figure 1)) who are toilet trained and able to communicate the presence of UTI symptoms

•Selected infants and preverbal children with low-grade VUR whose families prefer this approach and are able and willing to promptly seek medical attention for symptoms that suggest a possible UTI

For patients with high-grade VUR (grades III to V), we generally prefer antibiotic prophylaxis because it is associated with a lower risk of recurrent UTI. (See 'Antibiotic prophylaxis' below.)

●Family counseling – If surveillance is selected, the family/caregiver needs to be vigilant and must seek medical attention whenever there are symptoms suggestive of UTI or unexplained fever. They should be informed that recurrent febrile UTI can lead to kidney scarring, which may lead to hypertension and chronic kidney disease, and that delayed initiation of treatment (eg, greater than 24 to 48 hours after onset of fever due to UTI) is associated with increased risk of kidney scarring [11]. Additional follow-up includes periodic imaging to monitor VUR, kidney growth, and development of scarring. The family's/caregiver's social situation should be assessed for any challenges that might interfere with their role in active surveillance and follow-up. (See 'Follow-up' below.)

●Evidence – Active surveillance has been promoted as a reasonable management option based on the results of two systematic reviews that reported antibiotic prophylaxis (medical therapy) versus placebo or no treatment did not reduce the risk of UTI or kidney scarring [12,13]. However, any conclusion based on these publications needs to be viewed with caution because of the degree of heterogeneity of the studies including significant differences in methodology (eg, definition of UTI, grade of reflux) and study populations (eg, circumcision status, patient age) [14].

In contrast, the subsequently published Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial of 607 children (age range two months to six years) showed a lower risk of recurrent febrile or symptomatic UTI for children assigned to prophylactic antibiotics (trimethoprim-sulfamethoxazole [TMP-SMX]) versus those assigned to placebo [15]. However, there was no difference in the incidence of kidney scarring between the two groups during the two-year follow-up period as initially reported. Of note, in this cohort, children with grades III or IV VUR were more likely to have febrile or symptomatic UTI than those with grades I or II VUR (23 versus 14 percent). In subgroup analysis, TMP-SMX prophylaxis was associated with a lower risk of recurrent febrile or symptomatic UTI in patients with grades I or II VUR (hazard ratio [HR] 0.32, 95% CI 0.16-0.61). Antibiotic prophylaxis appeared to be associated with a lower risk of recurrent febrile or symptomatic UTI in patients with grades III or IV VUR, but this did not reach statistical significance (HR 0.66, 95% CI 0.40-1.09). A subsequent analysis reported that the prophylactic intervention group had reduced scarring compared with the control group [16].

A systematic review that included the RIVUR trial also concluded that prophylactic antibiotics reduced the risk of febrile and symptomatic UTI in children with VUR [17]. However, there was a higher risk of a UTI due to antibiotic-resistant bacteria and there appeared to be no effect on the risk of developing kidney scars. In this analysis, there was considerable heterogeneity among the studies including study design and quality. An additional study using data from the same cohort proposed a predictive model to identify which children with VUR might benefit from antibiotic prophylaxis, based on VUR grade, serum creatinine, age, sex, and presenting UTI symptoms [18]. Using this model, approximately 60 percent of children would qualify for watchful waiting rather than antibiotic prophylaxis, but these children still had some risk for recurrent UTI.

Antibiotic prophylaxis — Medical therapy for VUR consists of daily prophylactic administration of an antibiotic. It is based on the assumptions that daily antibiotic therapy results in sterile urine and the reflux of sterile urine does not cause kidney damage. This strategy often helps avoid surgery because VUR spontaneously resolves in most cases.

Indications — Decisions about antibiotic prophylaxis must be individualized, but the available evidence and clinical experience support giving antibiotics to the following groups of patients [19]:

●Children with moderate to severe VUR (grades III to IV)

●Children with mild VUR (grades I and II) and any of the following:

•History of recurrent UTIs

•Bladder and bowel dysfunction (BBD; because of increased risk for infection)

•Unable or unwilling to adhere to the requirements of surveillance therapy, including presenting promptly for evaluation of fever or other symptoms of possible UTI

•Kidney scarring (eg, on a dimercaptosuccinic acid [DMSA] renal scan, if performed)

•Congenital anomalies of the kidneys and urinary tract (CAKUT)

In addition, antibiotic prophylaxis may be preferred for infants or younger nontoilet-trained children with mild or moderate VUR; the surveillance approach is more difficult for this age group because they are often unable to communicate symptoms of an infection. However, surveillance without antibiotic prophylaxis is an option for parents/caregivers who prefer not to use prophylactic antibiotic therapy and are willing and able to present promptly for evaluation if the child develops symptoms of UTI and return for follow-up and monitoring, including periodic imaging to reassess VUR (contrast-voiding cystourethrogram [VCUG] or radionuclide cystogram [RNC]). (See 'Medically managed patients' below.)

Evidence — Large-scale studies continue to show an advantage to antibiotic prophylaxis, in that recurrent febrile UTIs are less common. A discussion with the families should determine whether they prefer a program of prophylaxis or surveillance. Socioeconomic considerations should also be considered, such as the availability of primary care, likelihood of close follow-up, and ability to pay for medication.

●Antibiotic prophylaxis versus surveillance – The relative efficacy of prophylactic antibiotic therapy versus no prophylaxis (surveillance) in children with VUR has been studied in clinical trials and meta-analyses [15,17,20]. The largest trial was the RIVUR trial, a multicenter trial involving 607 children diagnosed with VUR after a febrile UTI who were randomly assigned to receive daily TMP-SMX or placebo for two years [15]. Recurrent febrile or symptomatic UTIs occurred less frequently in children receiving TMP-SMX (13 versus 24 percent; HR 0.50, 95% CI 0.34-0.74).

Subgroup and post hoc analyses of the RIVUR trial explored factors predictive of greater benefit from antibiotic prophylaxis in children with VUR:

•In subgroup analysis, the treatment effect of antibiotic prophylaxis was greater in children with BBD (HR 0.21, 95% CI 0.08-0.58) and in children whose first UTI was febrile (HR 0.41, 95% CI 0.26-0.64) compared with the overall trial cohort [15]. Similar findings were seen in a separate analysis, in which antimicrobial prophylaxis was most beneficial for toilet-trained children with BBD [1].

•In a post hoc analysis of the RIVUR trial, researchers categorized patients as either high risk or low risk for recurrent UTI; the high-risk group included uncircumcised males, patients with associated BBD or constipation, and those with grade IV VUR [21]. In high-risk patients, prophylactic TMP-SMX was associated with a considerably lower rate of recurrent UTI (11 versus 32 percent; HR 0.27, 95% CI 0.13-0.57), whereas in low-risk patients, this intervention had a modest and statistically nonsignificant difference (14 versus 19 percent; HR 0.71, 95% CI 0.42-1.18). This study also highlights how uncircumcised males with any grade of reflux are at increased risk of UTI. (See 'Uncircumcised males' above.)

•A cost-utility analysis of the same cohort suggested that long-term antibiotic prophylaxis was most cost effective for children with grade IV VUR [22]. By contrast, for children with grades I to III VUR, antibiotic prophylaxis was less cost effective; for those children, it was not clear whether surgical intervention or surveillance off of medication was the most cost-effective approach.

•The impact of treatment adherence was noted in a secondary analysis that compared the least adherent patients (adherence <70 percent of the time) to the most adherent patients (adherence >96 percent of the time) [23]. The least adherent group was more likely to have a recurrent UTI (odds ratio 2.5, 95% CI 1.1-5.6) and was at higher risk of kidney scarring (odds ratio 24.2, 95% CI 3.0-197).

For young infants with high-grade VUR and no history of UTI, benefits of primary antibiotic prophylaxis are supported by a separate randomized trial [24]. The trial enrolled 292 infants one to five months of age with high-grade VUR (grade III or above) and randomized them to treatment with antibiotics (most often amoxicillin-clavulanate) or observation for two years. Antibiotic prophylaxis reduced the incidence of first symptomatic UTI (21 versus 36 percent; HR 0.55, 95% CI 0.35-0.86), with no significant differences in new kidney scars or kidney function but increased occurrence of antibiotic-resistant organisms in urine cultures. In contrast with the RIVUR trial, this study population had no prior UTIs at study enrollment and participants were also younger and male predominant (mostly uncircumcised) and had more CAKUT. By contrast, RIVUR and other similar trials reflect a more common clinical population with VUR in North America, ie, primarily girls who present after a UTI [15,25].

●Antibiotics versus surgery – Data from clinical trials and a systematic review have demonstrated comparable long-term kidney outcomes (recurrent UTI and scarring) in patients treated with either prophylactic antibiotics or surgical correction [12,26-29]. In particular, the choice of therapy does not impact the long-term kidney outcome in children with severe bilateral disease who are at increased risk for chronic kidney disease (ie, hypertension, impaired kidney function, and, in some, end-stage kidney disease) [29].

Agents and dosing — Antimicrobial agents most commonly used for prophylaxis are (table 1):

●Age <2 months – For this age group, we use amoxicillin, unless the infant has a penicillin allergy. Cephalexin is a reasonable alternative. We use these antibiotics because alternative antibiotics should be avoided in this age group due to potentially serious adverse effects.

●Age ≥2 months – After two months of age, we switch to either TMP-SMX or nitrofurantoin. These antibiotics are preferred over amoxicillin, ampicillin, or cephalosporins because they have lower rates of antibiotic resistance. TMP alone is also an option, if available.

Antibiotic agents may be changed if significant side effects, breakthrough UTI, or antibiotic resistance develop.

Complications — Complications of medical therapy include:

●Adverse effects – Adverse effects of long-term administration of prophylactic antibiotics include nausea and vomiting, diarrhea, abdominal pain, increased antibiotic resistance, marrow suppression, and, rarely, Stevens-Johnson syndrome [30]. However, in the RIVUR trial, no serious adverse effects other than antimicrobial resistance were noted [15,31,32].

Sulfonamides and nitrofurantoin should be avoided in infants <2 months old because they are associated with increased risk of neonatal hyperbilirubinemia. Other side effects of oral solutions of TMP in neonates are due to the inclusion of sodium benzoate ("gasping syndrome") and propylene glycol (respiratory depression).

●Antibiotic resistance – When breakthrough infection occurs, the organism is more likely to demonstrate antibiotic resistance including multidrug resistance; poor adherence might increase the risk of both recurrent UTI and antibiotic resistance.

Duration of therapy — Antibiotic prophylaxis is discontinued when VUR resolves spontaneously or improves to the point of being not clinically significant (as documented by VCUG, RNC, or contrast-enhanced voiding urosonography) or is surgically corrected.

In addition, some experts stop prophylaxis therapy in older children with persistent mild or moderate VUR once they have completed toilet training because the risk of recurrent urinary infection diminishes with age [33-35]. However, the optimal age of discontinuation is not well established, due to the lack of high-quality data.

Besides age, discontinuation of prophylaxis generally also depends on [36]:

●Toilet trained

●No BBD

●No evidence of kidney scarring

●No recent UTI (eg, within the past year)

●Family is able and willing to adhere to surveillance, which requires vigilance for symptoms of possible UTI and prompt presentation for diagnosis and treatment

If the child develops a UTI after discontinuation of antibiotic prophylaxis, they might require reimaging to see if VUR is present. If there is recurrent or persistent VUR, antibiotic prophylaxis should be resumed and surgical correction may be considered. Adolescent females with persistent VUR should be counseled about the higher risk of pyelonephritis during pregnancy (particularly if kidney scarring is present), and management options including surgical correction should be reviewed. (See 'Medically managed patients' below and "Urinary tract infections and asymptomatic bacteriuria in pregnancy", section on 'Acute pyelonephritis'.)

Surgical treatment — Surgical treatment corrects the anatomy at the refluxing ureterovesical junction. The approaches used are surgical reimplantation (via open surgery, laparoscopy, or robotic-assisted laparoscopic approach) and endoscopic correction. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Definition and pathogenesis'.)

Indications — We generally suggest surgical correction for patients with (figure 1 and algorithm 2):

●Moderate or severe VUR (grades III to V) at any age, plus any of the following:

•One or more breakthrough UTIs despite adherence to optimized prophylactic antibiotic therapy

•New kidney scarring or kidney changes

•Cannot tolerate prophylactic antibiotic therapy

•Family unwilling or unable to adhere to medical management (prophylactic antibiotics, seeking medical attention for fever or symptoms suggesting UTI, and long-term follow-up)

●Moderate or severe VUR that persists for one or more years of follow-up (despite appropriate management of BBD, if present). For this group, we generally prefer surgery for those with grades IV or V reflux and offer it as an option to those with grade III VUR. Surgery is deferred initially because VUR may spontaneously resolve in some patients. However, it is less likely to resolve if it persists for a year or longer. The family's preferences are important to determine the timing of switching from medical management to surgery; different families have different thresholds for how long is "long enough."

Clinical trials indicate that medical and surgical management are equally effective in reducing the incidence of UTI, pyelonephritis, and kidney scarring [26,27]. However, surgical correction is more invasive and typically is not the initial intervention used for most children with VUR. In particular, surgical correction is not suggested as initial management for patients with grades I and II VUR, because there is a high likelihood of spontaneous resolution and a low risk of kidney scarring for this group of patients.

Procedures — If surgical intervention is chosen, any of the following procedures is reasonable. The choice is primarily driven by the surgeon's experience and comfort with the technique. It may also be influenced by the family's preference after discussing the modest differences in efficacy and risks, as outlined below.

Open surgical reimplantation — Open surgical reimplantation of ureters is a highly successful procedure, with reported correction rates of 95 to 99 percent regardless of the severity of VUR [37-41]. These excellent outcomes are reported from major tertiary centers and depend on the skills of an experienced surgical staff.

Open procedures are performed with the following approaches:

●Intravesical approach – In the intravesical approach, the bladder is opened and the ureters are reimplanted by tunneling a ureteral segment inside the detrusor (bladder wall muscle), thereby creating a submucosal tunnel that is long enough to act as a flap valve (figure 2) [42]. The basic technique was described by Politano and Leadbetter, and subsequent modifications are named after surgeons who developed each of the variants (eg, Cohen, Glenn-Anderson).

●Extravesical approach – In this approach, reimplantation is performed without opening the bladder and is known as the Lich-Gregoir procedure (figure 3). As with the intravesicular approach, the distal ureter is placed into a longer submucosal tunnel, which acts as a flap valve. The extravesical approach has been associated with shortened hospital stays. Bilateral extravesical ureteral reimplantation has been associated with postoperative urinary retention (although rare), requiring prolonged catheterization.

Regardless of technique, the patient may require postoperative bladder drainage via a urinary catheter and an in-hospital admission that usually lasts from one to several days. In a small percentage of patients, there may be persistent VUR on the initial postoperative VCUG; however, VUR generally resolves spontaneously without need for further intervention [41]. New contralateral low-grade reflux can be seen on the nonoperated side after unilateral reimplantation. It most often spontaneously resolves and is of little clinical consequence [43].

Laparoscopic and robotic-assisted laparoscopic reimplantation — Robotic-assisted laparoscopy uses an extravesical (or, less commonly, a transvesical) approach (figure 3) to reconfigure the ureterovesical junction in the same manner as in open reimplantation.

It is unclear if there are any advantages to laparoscopic surgery, given the low morbidity and high success rate of open surgery and mixed evidence regarding the relative success, risks, and costs of these techniques. Two case series reported comparable success rates between children who underwent robotic-assisted reimplantation compared with patients undergoing open surgical correction during the same time periods [44,45]. However, multicenter reviews from United States tertiary centers reported a lower success rate and higher complication rate associated with laparoscopic and robotic-assisted reimplantation versus open reimplantation [46-49].

Transvesical laparoscopic or so-called "vesicoscopic" ureteral reimplantation is one of the newer innovations. The surgery is done entirely within the bladder, as opposed to the more common laparoscopic approach via the abdominal cavity. Success rates of greater than 95 percent have been reported in early series [50,51]. It remains to be seen if this becomes more widely adopted.

Endoscopic correction — Endoscopic correction, a less invasive ambulatory procedure, injects a periureteral bulking agent via a cystoscope, which changes the angle and perhaps fixation of the intravesical ureter, thereby correcting VUR [52].

●Techniques – In the United States, the two most commonly used techniques use a copolymer of dextranomer/hyaluronic acid (Dx/HA or DEFLUX) but use different injection sites (figure 4) [53]:

•Hydrodistension implantation technique, which places the bulking agent within the ureteral tunnel

•Subureteral transurethral injection, which places the bulking agent just below the ureteral orifice

●Efficacy – The success rate for correcting VUR with DEFLUX in one or more procedures ranges from 75 to over 90 percent [8,54-62]. The success rate for initial correction of VUR (by ureter) varies by the severity of reflux and anatomic variables (figure 1).

This was illustrated by a systematic review of endoscopic procedures on 7303 ureters from 89 selected reports [61]. Although there was marked heterogeneity among the results primarily related to between-study variability, multiple regression analysis demonstrated that preoperative VUR grade was the single most important factor affecting successful correction outcome:

•Grade I – 89 percent (95% CI, 69-90 percent)

•Grade II – 83 percent (95% CI, 76-90 percent)

•Grade III – 71 percent (95% CI, 64-79 percent)

•Grade IV – 59 percent (95% CI, 59-66 percent)

•Grade V – 62 percent (95% CI, 54-72 percent)

However, one to two years postprocedure, there is an overall delayed failure (or recurrence) rate, with reported rates that range from 5 to 25 percent [49,52,60,63-65]. As an example, in the Swedish Reflux Trial of 203 children between one and two years of age with grades III to IV VUR, there was a 71 percent resolution of VUR in patients assigned to endoscopic correction, but recurrence occurred in 20 percent of corrected patients after a two-year follow-up [64,65]. The reasons for the delay in recurrence of VUR may be shifting of the implanted material from the initial injection site or resorption of the material over time in some patients.

The success rate of a second endoscopic procedure after an initial failed injection is high, ranging from 70 to 90 percent [58,59,66,67]. The endoscopic approach also has been rarely utilized as a salvage procedure, correcting VUR in patients who failed a previous open surgical reimplantation, with a reported success rate as high as 65 percent [58].

●Complications – Reported complications after endoscopic correction include [52]:

•Postprocedure UTI and VUR recurrence – There appears to be a risk of postprocedure febrile UTIs in patients who develop recurrent reflux [68,69]. This was illustrated by a study of 167 patients that reported an episode of febrile UTI in seven patients with recurrent VUR [68]. This finding suggests that febrile UTI after endoscopic correction should be an indication for reevaluation by cystography.

•Contralateral VUR – VUR in the contralateral untreated side has been reported following endoscopic treatment [70]. Similar to contralateral reflux after open surgery, this is usually mild and resolves spontaneously.

•Ureteral obstruction – In a retrospective review of 745 patients with 1155 ureters who underwent correction, the incidence of postoperative ureteral obstruction was less than 1 percent of treated patients [71].

Awareness of the history of prior endoscopic treatment for VUR is important to avoid misdiagnosis of nephrolithiasis on imaging later in life. If computed tomography (CT) or magnetic resonance imaging (MRI) is performed, the endoscopic implants may be identified as either high- or low-density lesions [72,73]. High-density lesions, which are due to calcification of the implant, resemble urinary calculi on CT and ultrasonography [74], whereas a low-density implant may be mistaken as an ureterocele or a seminal vesicle cyst on MRI. Although the long-term significance of calcification of implants is unknown, there have been no reports of symptoms related to these lesions.

FOLLOW-UP

Medically managed patients — In patients treated with antibiotic prophylaxis or surveillance (watchful waiting), ongoing monitoring is needed to detect recurrent urinary tract infection (UTI), detect when and if spontaneous resolution of reflux occurs, and assess the general health of the child [19]. Long-term follow-up is also suggested as the long-term risk of kidney scarring and its potential sequelae remain uncertain. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Further evaluation' and "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Complications'.)

●General measures – Follow-up consists of:

•General evaluation – Measurements of height, weight, and blood pressure.

•Urine cultures and urinalysis – Required whenever there are urinary symptoms suggestive of UTI or unexplained fever. (See "Urinary tract infections in infants older than one month and children younger than two years: Clinical features and diagnosis", section on 'Laboratory evaluation and diagnosis'.)

•Monitoring of reflux – This is done by either contrast-voiding cystourethrogram (VCUG) or radionuclide cystogram (RNC). Contrast-enhanced voiding urosonography, which is available in some centers, is another option. We typically perform one of these studies every 12 to 24 months, but practice varies and there is little supportive evidence to guide timing. Some families and clinicians may opt for observation without prophylaxis or radiographic reevaluation for children with low-grade reflux who have remained infection free for a period of time (algorithm 1). This may be most appropriate for older children who can report the symptoms of a UTI. (See 'Duration of therapy' above.)

●Other imaging – The need for and value of ongoing imaging of the kidneys remains uncertain.

•Dimercaptosuccinic acid (DMSA) renal scan – Selective monitoring for kidney scarring by DMSA renal scan is advised for patients at risk for significant abnormalities that may affect their care, as outlined in a guideline from the American Urology Association [75]. In our practice, we selectively obtain DMSA renal scans at the time of presentation in patients with grades III to V reflux if there are kidney parenchymal or size abnormalities on ultrasound or a history of multiple episodes of pyelonephritis. Some other clinicians may opt to perform initial baseline scans in all children, even those with lower VUR grades (I and II). DMSA scan evidence of kidney scarring and pyelonephritis has been found in children at presentation with grades I and II VUR, although this is less common than in those with higher-grade VUR [15].

During follow-up, DMSA renal scans are not routinely repeated. However, follow-up DMSA renal scans may be indicated for selected patients with concerns for kidney scarring on ultrasound (abnormal kidney contour, small kidney size) or VCUG (such as severe blunting of the calyces or intrarenal reflux) or those with a history of UTI who develop hypertension. New kidney scarring or evidence of pyelonephritis would be a reason to suggest a change in management (eg, antibiotic prophylaxis for those managed by surveillance, surgical correction for those managed by antibiotic prophylaxis). The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial reported significant interobserver variability in the reporting of DMSA renal scans [76].

•Kidney ultrasound – We do not perform kidney ultrasound during routine monitoring of VUR, because it has low sensitivity both for VUR and for detecting scarring, unless there is gross atrophy [77]. However, a follow-up ultrasound performed several years later may be helpful to assess kidney growth, especially for patients with significant scarring based on renal scan.

●Recurrent or breakthrough UTI – If symptomatic infection occurs, a change in the treatment regimen should be considered [75]. As examples:

•For children who develop UTI recurrence while being managed by surveillance, we suggest starting prophylactic antibiotics.

•For children who develop UTI recurrence while on antibiotic prophylaxis (breakthrough UTI), the UTI is first treated with an appropriate regimen, then:

-If the VUR is mild, we suggest changing antibiotics (or prophylaxis with two antibiotics) if the organism is resistant to the current regimen. Surgical correction should be considered after one or more breakthrough infections despite appropriate prophylaxis, using shared decision-making with the family.

-If the VUR is severe, we suggest surgical correction.

●Discontinuation of antibiotics – Because of the paucity of data, indications of when to discontinue prophylactic antibiotics are uncertain, as described above. However, the presence of kidney scarring argues against discontinuation of antibiotic prophylaxis in those with persistent reflux. (See 'Duration of therapy' above.)

Teenage girls should be made aware that the presence of reflux increases the risk of pyelonephritis during pregnancy and that they should be carefully monitored at that time unless they opt for surgical correction [78,79]. (See "Urinary tract infections and asymptomatic bacteriuria in pregnancy".)

Surgically treated patients

●After open or laparoscopic surgery – Most surgeons obtain a kidney and bladder ultrasound approximately four to six weeks after surgery to evaluate for silent obstruction from the procedure, which is fortunately rare. Ultrasound performed early after surgery (ie, one to two weeks postoperatively) may show transient worsening of hydroureteronephrosis, so imaging during this initial time period is discouraged unless the patient is not doing well clinically.

Many centers perform postoperative VCUG or RNC only if there is a documented UTI following surgical correction, given the recognized high success rates for these procedures. However, some other centers routinely perform one of these studies to determine the success of the procedure [75]. If performed, the study should be done at least three to six months after surgical correction. If there is one normal VCUG or RNC, repeat studies are generally unnecessary because VUR is unlikely to reappear, including after recurrent UTI [80,81]. However, those with recurrent UTIs should be evaluated for associated bladder and bowel dysfunction (BBD). (See "Evaluation and diagnosis of bladder dysfunction in children".)

●After endoscopic therapy – As with open antireflux surgery, most surgeons also obtain a kidney and bladder ultrasound four to six weeks after endoscopic treatment to assess for silent obstruction.

Children treated with endoscopic therapy have a moderate risk of recurrent VUR (see 'Endoscopic correction' above). As a result, we perform a VCUG approximately three to six months after endoscopic correction. For patients with recurrent febrile UTIs, we repeat the imaging in addition to evaluating and managing any associated BBD. When considering endoscopic therapy, families should be counseled that this approach is associated with a higher risk of recurrent VUR and UTIs compared with open or laparoscopic surgery, necessitating reimaging and possible retreatment.

Long-term follow-up — Following the resolution of VUR either spontaneously or surgically, long-term follow-up should be provided for those with kidney scarring. This includes annual assessments through adolescence, which include measurements of growth (height and weight) and blood pressure, as well as urinalysis to detect proteinuria or bacteria, as recommended in an American Urology Association guideline [8]. In addition, patients with resolved VUR should be reevaluated if they have a febrile UTI, including evaluation for BBD and recurrent VUR. Families should be made aware of the potential patient complications of hypertension and impaired kidney function as well as the increased risk of VUR in first-degree relatives.

The frequency, utility, and method of detecting kidney scarring have not been clearly defined. DMSA renal scan is the most sensitive measure for detecting kidney scarring. Kidney ultrasound is not as sensitive in detecting kidney scars as DMSA scan and, as a result, has not been as useful in follow-up [77,82]. However, a kidney ultrasound performed every two or three years may help monitor kidney growth, especially for patients with significant scarring. People with kidney scarring require lifelong monitoring for recurrent UTI, proteinuria, hypertension, and chronic kidney disease [83]. The need for DMSA renal scan is determined on a case-by-case basis, depending on how the information would affect clinical management. For example, nephrectomy may be considered for a patient with severe hypertension if the DMSA renal scan demonstrates a significant differential function, with the affected kidney demonstrating less than 10 to 15 percent function.

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vesicoureteral reflux".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Vesicoureteral reflux in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder into the ureter and kidney. Management is directed at minimizing the risk of recurrent urinary tract infections (UTIs), which can cause kidney scarring.

●Treatment options – Therapeutic options for VUR include:

•Surveillance (watchful waiting), consisting of observation and prompt treatment of intercurrent episodes of UTI. This can be difficult in infants because symptoms can be subtle and nonspecific. Close monitoring is important because delayed initiation of treatment for pyelonephritis is associated with increased risk of kidney scarring. (See 'Surveillance' above.)

•Antibiotic prophylaxis to lower the risk of recurrent UTI, consisting of a single daily dose of antibiotic. (See 'Antibiotic prophylaxis' above.)

•Surgical treatment correcting the anatomy at the refluxing ureterovesical junction. Surgical approaches include open or laparoscopic surgical reimplantation (typically requiring overnight hospitalization) and endoscopic correction (typically ambulatory). Endoscopic correction is less invasive but is also associated with somewhat lower initial success and greater risk of VUR recurrence. (See 'Surgical treatment' above.)

●Address associated risk factors, if present

•Bladder and bowel dysfunction (BBD) – BBD is a common finding in older children (toilet trained) with VUR. Children with VUR and BBD are at increased risk for breakthrough UTI, longer time for VUR resolution, and increased failure rate of surgical correction compared with patients with only VUR. Thus, identification and treatment of BBD are required for any patient with VUR; management is discussed separately. (See 'Bladder and bowel dysfunction' above and "Management of bladder dysfunction in children".)

•Uncircumcised males – For uncircumcised males, we discuss strategies to reduce the risk of UTI, which include the option of interventions to manage phimosis, if present, or circumcision. These considerations are especially important for those with high-grade VUR. Families who opt not to circumcise should be made aware of the association of UTIs and the intact foreskin. (See "Neonatal circumcision: Risks and benefits", section on 'Reduction in urinary tract infection' and "Care and complications of the uncircumcised penis in infants and children", section on 'Management of physiologic phimosis'.)

●Management of VUR according to severity – Our management approach is based, in part, on the severity of VUR (figure 1). Additional individual factors that contribute to management decisions include the presence of BBD (in toilet-trained children), individual risk factors for chronic kidney disease (eg, kidney scarring from congenital dysplasia or recurrent pyelonephritis), and parent/caregiver preferences. (See 'Approach based on vesicoureteral reflux severity' above.)

•Mild VUR – Our suggested approach for infants and children with mild (grades I to II) VUR is as follows (algorithm 1) (see 'Grades I and II' above):

-Patients with associated BBD or other risk factors – For patients with mild VUR and associated BBD, recurrent UTIs, kidney scarring, or congenital anomalies of the kidney and urinary tract (CAKUT), we suggest prophylactic antibiotic therapy (table 1) rather than surveillance (Grade 2B). Children with BBD are at increased risk for febrile UTI, and antibiotic prophylaxis reduces this risk. Prophylactic antibiotics also may be advantageous for infants and children who are not toilet trained, because surveillance is more challenging.

-Children without BBD or other risk factors – For children with mild VUR without BBD or other risk factors, either prophylactic antibiotic therapy or surveillance is a reasonable option and we make decisions collaboratively with the family. Antibiotic prophylaxis is appropriate if the family is unable or prefers not to adhere to the requirements for surveillance, especially presenting promptly for evaluation of suspected UTI. (See 'Surveillance' above and 'Antibiotic prophylaxis' above.)

•Moderate or severe VUR – For most children with grades III to V reflux, we suggest initial treatment with antibiotic prophylaxis rather than surveillance (algorithm 2 and table 1) (Grade 2B). Compared with surveillance, antibiotic therapy reduces the risk for febrile UTIs, although the benefits for preventing kidney scarring are uncertain. (See 'Grades III to V' above and 'Evidence' above.)

Subsequently, we suggest surgical correction rather than ongoing antibiotic prophylaxis for patients with any of the following (Grade 2C):

-Recurrent UTI

-Intolerance or difficulty with adherence to prophylactic antibiotic therapy

-New kidney scarring

-Grade IV or V reflux that persists for one or more years of follow-up (despite appropriate management of BBD, if present)

Children with these features are at risk for recurrent UTIs, kidney scarring, and chronic kidney disease. Surgery is highly effective for resolving VUR. Furthermore, moderate or severe VUR is less likely to resolve spontaneously with advancing age. Surgery is also a reasonable option for other children whose families choose to proceed with definitive treatment rather than ongoing antibiotic prophylaxis. (See 'Surgical treatment' above.)

●Recurrent UTI – For children who experience a recurrent UTI during follow-up, the first step is to treat the acute infection, as discussed separately. (See "Urinary tract infections in infants older than one month and children younger than two years: Acute management, imaging, and prognosis" and "Acute simple cystitis in children older than two years and adolescents: Management".)

In addition, modification of the ongoing treatment plan is generally warranted (see 'Medically managed patients' above):

•For children who develop UTI recurrence while being managed by surveillance, we suggest starting prophylactic antibiotics (table 1) (Grade 2B).

•For children who develop UTI recurrence while on antibiotic prophylaxis (breakthrough UTI), we suggest changing antibiotics if the VUR is mild and the organism is resistant to the current regimen (Grade 2C), as well as surgical correction if the VUR is moderate or severe (as outlined above).

●Follow-up

•During antibiotic prophylaxis or surveillance – Patients who are treated with antibiotic prophylaxis or surveillance require urine testing (urinalysis and properly collected urine culture) whenever there are symptoms suggestive of UTI or unexplained fever. They also require periodic reevaluation with voiding cystourethrogram (VCUG) or radionuclide cystogram (RNC) to monitor for resolution of the VUR. (See 'Medically managed patients' above.)

Antibiotic prophylaxis can be discontinued if (see 'Duration of therapy' above):

-The VUR resolves, or

-The child is toilet trained and has mild reflux with no BBD, kidney scarring, or recent UTIs (see 'Duration of therapy' above)

•After surgery – Following surgical correction, a kidney ultrasound is performed approximately four to six weeks postoperatively to assess for obstruction. Children treated with an endoscopic procedure are at risk for recurrent VUR. Accordingly, they should be reevaluated with VCUG or RNC if they have a postoperative febrile UTI and some centers routinely perform a VCUG or RNC several months after the procedure. (See 'Surgically treated patients' above.)

•Long term – Long-term follow-up in children includes annual assessment of linear growth, measurement of blood pressure, and urinalysis. Families should be made aware of the association of VUR and kidney scarring, with long-term increased risk of chronic kidney disease (eg, hypertension, kidney function impairment, proteinuria). (See 'Long-term follow-up' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Gordon McLorie, MD, FRCSC, FAAP, and John Herrin, MBBS, FRACP, who contributed to earlier versions of this topic review.