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Management of vesicoureteral reflux

Management of vesicoureteral reflux
Authors:
Tej K Mattoo, MD, DCH, FRCP
Saul P Greenfield, MD
Section Editors:
Laurence S Baskin, MD, FAAP
F Bruder Stapleton, MD
Deputy Editor:
Laurie Wilkie, MD, MS
Literature review current through: Dec 2022. | This topic last updated: Apr 09, 2021.

INTRODUCTION — Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder into the upper urinary tract. The clinical significance of VUR has been based on the premise that it predisposes patients to acute pyelonephritis by transporting bacteria from the bladder to the kidney, which may lead to renal scarring, hypertension, and end-stage renal disease (ESRD). However, aspects of this long-held belief have been increasingly questioned. As a result, there is controversy regarding the optimal management of patients with VUR.

The management of VUR will be reviewed here. The presentation, diagnosis, and clinical course of VUR are discussed elsewhere in the program. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

MANAGEMENT

Goal — The goals of VUR management include:

Prevention of recurrent urinary tract infections (UTIs)

Prevention of worsening renal damage (eg, renal scarring)

Minimization of morbidity of treatment and follow-up

Identification and treatment of children with bladder and bowel dysfunction (BBD)

Approach — The management of VUR varies from center to center because there are insufficient data to establish evidence-based consensus guidelines. Therapeutic choices to manage VUR include watchful waiting (surveillance), antibiotic prophylaxis, and surgical correction. In addition, it is important to identify and treat older, toilet-trained children with BBD because they are at risk for recurrent urinary tract infection, pyelonephritis, and worsening of VUR and are less likely to have spontaneous VUR resolution.

Our management approach is based on the available evidence and individualizes the management based on:

Presence of BBD in toilet-trained-age children

Likelihood of spontaneous resolution

Risk of renal scarring

Assessment of compliance

Preference of parents/caregivers regarding choice of intervention

We divide our management approach based on the severity of VUR (figure 1) since increasing severity of VUR is associated with increased risk of febrile UTI recurrence and renal scarring as well as a decreased likelihood of spontaneous resolution. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux".)

Bladder and bowel dysfunction — BBD is a common finding in patients with VUR in the toilet-trained age group and is more common in girls [1-5]. Patients with both BBD and VUR have a higher incidence of breakthrough UTI (any UTI while on prophylactic antibiotic therapy), longer time for VUR resolution, and increased failure rate of surgical correction than patients with only VUR [1-3,6]. Thus, it is important to identify and treat BBD in any patient with VUR.

Symptoms and clinical findings of BBD include urge incontinence, infrequent voiding, recurrent UTI, dysuria, abdominal pain, constipation, and 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 [7,8]. Interventions include laxatives, timed frequent voiding, pelvic floor exercises, behavioral modification, and, in some cases, anticholinergic therapy. (See "Management of bladder dysfunction in children".)

Grades III to V — We continue to treat children with grades III to V reflux (figure 1) since they are at risk for recurrent pyelonephritis and renal scarring and, potentially, chronic kidney disease (CKD) (algorithm 1). (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Kidney scarring'.)

Our approach is as follows:

Antibiotic prophylaxis – All patients regardless of age receive antibiotic prophylaxis. (See 'Antibiotic prophylaxis' below.)

Detection and treatment of BBD in the toilet-trained child – In patients with BBD, measures to improve bladder and bowel function are initiated with ongoing monitoring to see whether VUR spontaneously resolves or improves. A trial of therapeutic medical intervention should be provided before any surgical intervention is undertaken as the surgical failure rate is significant in patients with persistent BBD. (See 'Bladder and bowel dysfunction' above and "Management of bladder dysfunction in children".)

Indications for surgery – Surgical correction by open or endoscopic means for VUR that is not associated with other urologic abnormalities (eg, ureterocele) is considered and discussed with the family/caregivers for children with the following conditions. The choice of surgical intervention is dependent on the preference of the family/caregivers and expertise of each center. (See 'Surgical treatment' below.)

Grade IV/V reflux that persists in children beyond two or three years of age. Surgical correction should be delayed until two or three years of age since it is possible that VUR will spontaneously resolve. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Likelihood of resolution'.)

Children who fail medical therapy with breakthrough infections.

Children who have significant side effects from continuous prophylactic antibiotics. (See 'Complications' below.)

Noncompliance with a long-term medical regimen (antibiotic prophylaxis or failed follow-up after a febrile illness).

Family/caregivers preference – In all cases, the benefits and potential adverse effects of surgical and medical therapy are discussed with the family/caregivers. The preference of the family/caregivers plays a major role in the final therapeutic decision.

Grade I and II — Children with grade I or II reflux are at a low risk for pyelonephritis and renal scarring and are more likely to have spontaneous resolution of their VUR. For patients with BBD, measures to improve bladder and bowel function are initiated with follow-up to see whether VUR spontaneously resolves (algorithm 2). (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Kidney scarring' and "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Likelihood of resolution' and "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Recurrent urinary tract infection' and 'Bladder and bowel dysfunction' above.)

We provide the family/caregivers with information about the different treatment options for VUR (antibiotic prophylaxis, surveillance, or surgical correction) as well as the potential advantages of circumcision in uncircumcised males (see "Neonatal circumcision: Risks and benefits", section on 'Reduction in urinary tract infection'). The preference of the family/caregivers plays a major role in the final therapeutic decision.

Surveillance – In our practice, we consider this approach only in toilet-trained, verbal children, who are able to communicate symptoms in the presence of an infection, and families who understand and will be compliant in following medical instructions for follow-up. The need for prompt recognition of any subsequent urinary infection is emphasized. Additional infections would trigger discussion of either antibiotic prophylaxis or surgical management. (See 'Watchful waiting (surveillance)' below.)

Antibiotic prophylaxis – We give antibiotic prophylaxis to children who are not toilet-trained, because they usually are unable to communicate symptoms in the presence of an infection. For toilet-trained children, antibiotic prophylaxis is also given to patients with a history of recurrent UTI, those with BBD who are at risk for infection, and patients who are unable to adhere to the requirements of surveillance therapy. (See 'Antibiotic prophylaxis' below.)

Surgical correction – We do not suggest surgical correction as initial therapy for patients with grade I and II VUR, because there is a high likelihood of spontaneous resolution and a low risk of renal scarring and the long-term risk of renal scarring in patients with surgical correction is similar to that of those treated with medical therapy. If the family/caregiver desires, we will 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 VUR who have breakthrough infections on antibiotic prophylaxis. (See 'Surgical treatment' below.)

THERAPEUTIC OPTIONS

Watchful waiting (surveillance) — Watchful waiting consists of a regimen of surveillance and prompt treatment of intercurrent episodes of urinary tract infection (UTI). Families must seek medical attention when there are symptoms suggestive of UTI or unexplained fever. In our practice, watchful waiting is an option for patients with low-grade reflux (grades I and II (figure 1)) and who are toilet-trained and able to communicate the presence of UTI symptoms. For patients with high-grade reflux (grades III to V), as well as children who are not toilet-trained or are not able to communicate symptoms in the presence of an infection, we prefer antibiotic prophylaxis because it is associated with a lower risk of recurrent UTI. (See 'Antibiotic prophylaxis' below.)

If watchful waiting is selected, family/caregivers need to be aware that renal scarring is a potential consequences of recurrent febrile UTI, which may lead to hypertension and chronic kidney disease. The family/caregiver needs to be vigilant and must seek medical attention whenever there are symptoms suggestive of UTI or unexplained fever. Additional follow-up includes monitoring of VUR and renal scarring. The family/caregiver's social situation should be assessed for compliance since surveillance puts the onus on caregivers to promptly recognize a potential UTI and seek medical attention. (See 'Follow-up' below.)

Watchful waiting 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 renal scarring [9,10]. 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) [11].

In contrast, the subsequently published Randomized Intervention for 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 [12]. However, there was no difference in the incidence of renal scarring between the two groups during the two-year follow-up period as initially reported. Of note, in this cohort, children with grade III or IV VUR were more likely to have febrile or symptomatic UTI than those with grade 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 grade 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 grade III or IV VUR, but this did not reach statistical significance (HR 0.66, 95% CI 0.40-1.09). A subsequent analysis reported the prophylactic intervention group had reduced scarring when compared with the control group [13]. (See "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis", section on 'Prophylactic antibiotics'.)

A systematic review that included the RIVUR trial also reported similar results that prophylactic antibiotics reduced the risk of febrile and symptomatic UTI in children with VUR [14]. 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 renal scars. In this analysis, there was considerable heterogeneity among the studies including study design and quality.

Antibiotic prophylaxis — Medical therapy for VUR consists of daily prophylactic administration of an antibiotic agent. It is based on the assumptions that use of continuous antibiotics results in sterile urine and the continued reflux of sterile urine does not cause renal damage, as well as the observation that reflux spontaneously resolves in most cases.

Indications — In our practice, antibiotic prophylaxis is given to the following:

Patients with a history of UTI

All patients who are not toilet-trained with VUR regardless of the severity of grade, unless the family/caregiver prefers surveillance and is compliant with medical advice and care

All patients with bladder and bowel dysfunction (BBD) regardless of the severity of VUR

All patients with high-grade reflux (grade III to IV)

However, surveillance is an option for parents/caregivers who prefer not to use prophylactic antibiotic therapy and are compliant with medical advice and follow-up.

As noted above, the best evidence supporting the use of antibiotic prophylaxis versus surveillance is from the RIVUR trial. In this multicenter trial of children diagnosed with VUR, the effectiveness of TMP-SMX and placebo were compared over a two-year follow-up period [12]. Overall, children in the TMP-SMX group were less likely to have recurrent febrile or symptomatic UTI than those in the placebo group (13 versus 24 percent) (HR 0.50, 95% CI 0.34-0.74). In subgroup analysis, antibiotic prophylaxis was most effective 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). In a subsequent publication, prophylactic antibiotic was reported to be even more beneficial in patients who were at high-risk for recurrent UTI [15]. High-risk was classified as uncircumcised males with VUR, any patient with VUR and BBD or constipation, and patients with grade IV VUR with or without BBD or constipation. In the original cohort, the number needed to treat to avoid a recurrent UTI was eight, which decreases to five in the high-risk group and increases to 18 in the low-risk group. These results will be useful to determine a selective approach that identifies children who would most benefit from antibiotic prophylaxis and avoid unnecessary therapy for others.

In an analysis of the RIVUR data, antimicrobial prophylaxis appeared to be most beneficial for toilet-trained children who have BBD and VUR with a decrease in recurrent UTI with antimicrobial prophylaxis [1].

This study highlights that uncircumcised males with any grade of reflux are at increased risk of UTI. For these boys, the family/caregivers should be aware of the risk and elective circumcision should be offered as an option, either initially or after a subsequent infection. In addition, if there is any evidence of physiologic phimosis, it is reasonable to suggest topical corticosteroid therapy to allow complete retraction of the foreskin. (See "Care of the uncircumcised penis in infants and children", section on 'Physiologic phimosis'.)

Data from clinical trials and a systematic review have demonstrated comparable long-term renal outcome (recurrent UTI and scarring) in patients treated with either prophylactic antibiotics or surgical correction [9,16-19]. In particular, the choice of therapy does not impact the long-term renal outcome in children with severe bilateral disease who are at increased risk for CKD (ie, hypertension, impaired renal function, and, in some, end-stage renal disease [ESRD]) [19].

The impact of adherence to antibiotic prophylaxis was reviewed by a secondary analysis of the RIVUR study that reported that the least adherent patients (adherence <70 percent of the time) compared with the most adherent patients (adherence >96 percent of the time) were 2.5 times more likely (95% CI 1.1-5.6) to have a recurrent UTI (95% CI 1.1-5.6) and were at the higher risk of renal scarring (odds ratio [OR] 24.2, 95% CI 3.0-197) [20].

Agents and dosing — Antimicrobial agents most commonly used for prophylaxis include TMP-SMZ, TMP alone, or nitrofurantoin [21]. One daily dose is administered at bedtime.

The following are single daily prophylactic doses of commonly used antimicrobial agents:

TMP-SMX or TMP alone – Dosing is based on TMP at 2 mg/kg

Nitrofurantoin – 1 to 2 mg/kg

Amoxicillin, ampicillin, and cephalosporins are not generally recommended, because of the increased likelihood of resistant organisms [22]. However, these agents are used in infants below two months of age because sulfonamides, trimethoprim, or nitrofurantoin are associated with serious adverse effects (eg, hyperbilirubinemia) in this age group and should be avoided. (See 'Complications' below.)

The following are single daily prophylactic doses for these agents:

Cephalexin – 10 mg/kg

Ampicillin – 20 mg/kg

Amoxicillin – 10 mg/kg

Antibiotic agents may be changed because of significant side effects or resistance of organisms to the initial antibiotic choice.

Discontinuation prophylactic antibiotics — Antibiotic prophylaxis is discontinued when VUR resolves spontaneously or is surgically corrected, which is documented by contrast-voiding cystourethrogram (VCUG), contrast-enhanced voiding urosonography (ceVUS), or radionuclide cystogram (RNC). Although the evidence is not conclusive, some experts stop prophylaxis therapy in select older children with persistent VUR because the risk of recurrent urinary infection diminishes with age [23-25]. However, the age of discontinuation is not well established, due to the lack of high-quality data. Besides age, the timing for discontinuation of prophylaxis also depends on absence of BBD, toilet-training status, lack of evidence of renal scarring, and no recent UTI. Furthermore, discontinuation may be dependent upon the social situation and history of compliance. Families need to be counseled regarding prompt diagnosis and treatment of any subsequent infections. Additional infections might require reimaging to see if VUR is present. If there is recurrent or persistent VUR, antibiotic prophylaxis is resumed and surgical correction may be considered. Finally, adolescent females with persistent VUR should be counseled about the higher risk of pyelonephritis during pregnancy and management options including surgical correction should be reviewed. (See 'Discontinuation of medical therapy' below and "Urinary tract infections and asymptomatic bacteriuria in pregnancy", section on 'Acute pyelonephritis'.)

Complications — Complications of medical therapy include:

Adverse effects of long-term administration of prophylactic antibiotics include nausea and vomiting, abdominal pain, increased antibiotic resistance, marrow suppression, and, rarely, Stevens-Johnson syndrome [26]. However, in the previously discussed RIVUR trial of 607 children, no serious adverse effects other than antimicrobial resistance were noted [12,27].

Neonates – In neonates, sulfonamides and nitrofurantoin are associated with increased risk of neonatal hyperbilirubinemia, and as a result are avoided in young infants under the age of two months. Other neonatal side effects of oral solutions of trimethoprim are due to the inclusion of sodium benzoate ("gasping syndrome") and propylene glycol (respiratory depression).

Subsequent infection because of antibiotic resistance or lack of compliance [12]. Prophylaxis increases the risk of multidrug resistance among recurrent infections [28].

The need for periodic monitoring of VUR either by VCUG or RNC.

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

Indications — Clinical trials comparing medical versus surgical management demonstrate a similar decrease in the incidence of UTI and pyelonephritis and the development of renal scarring [16,17]. 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 for patients with grade I and II VUR, because there is a high likelihood of spontaneous resolution and a low risk of renal scarring for this subgroup of patients.

In our practice, surgical correction is reserved for the following patients based on severity of reflux (figure 1 and algorithm 1):

Children with grade IV/V reflux that persists beyond two or three years of age. Surgery is delayed until this age because VUR may spontaneously resolve during the first two or three years of age and is less likely to resolve beyond this age range.

Children with grade III to IV reflux:

Who cannot tolerate prophylactic antibiotic therapy

Who are not compliant with medical management (eg, prophylactic antibiotic therapy or follow-up after a febrile illness)

With breakthrough infections on prophylactic antibiotic therapy

Procedures

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 [29-33]. These excellent outcomes are reported from major tertiary centers and are dependent upon the skills of an experienced surgical staff.

Open procedures are based on the basic technique, described by Politano and Leadbetter, and include the following approaches:

Intravesical approach – In the intravesical approach, the bladder is opened (intravesical approach) and the ureters are reimplanted by tunneling a ureteral segment through the detrusor (bladder wall muscle), thereby creating a submucosal tunnel that is long enough to act as a flap valve (figure 2) [34]. Modifications of the basic technique, described by Politano and Leadbetter, 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).

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 [33].

Robotic-assisted laparoscopic reimplantation — Robotic-assisted laparoscopy uses either the extravesical open approach or less commonly a transvesical approach (figure 3). Although 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 [35,36], multicenter reviews from United States tertiary centers reported a lower success rate and higher complication rate associated with robotic assisted reimplantation versus open reimplantation [37,38].

Further studies are needed to determine the relative cost/benefit of robotic-assisted reimplantation versus open surgical reimplantation.

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 [39]. 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) [40].

Hydrodistension implantation technique (HIT), which places the bulking agent within the ureteral tunnel

Subureteral transurethral injection (STING), which places the bulking agent outside the ureteral orifice

The success rate for correcting VUR with DEFLUX in one or more procedures ranges from 75 to over 90 percent [41-49]. 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 the literature of 7303 ureters from 89 selected reports [48]. 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 rate, with reported rates that range from 5 to 25 percent [39,47,50-52]. As an example, in the Swedish Reflux Trial of 203 children between one and two years of age with grade 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 [51,52].

The success rate of a second endoscopic procedure after an initial failed injection is high, ranging from 70 to 90 percent [45,46,53,54]. 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 [45].

Complications — Reported complications after endoscopic correction include the following [39]:

Postprocedure UTI and VUR recurrence – There appears to be a risk of postprocedure febrile UTIs in patients who develop recurrent reflux [55,56]. This was illustrated by a study of 167 that reported an episode of febrile UTI in seven patients with recurrent VUR [55]. 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 [57].

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 [58].

In addition, endoscopic implants may be identified as either high- or low-density lesions by subsequent computed tomography (CT) or magnetic resonance imaging (MRI) [59,60]. High-density lesions appear to be due to calcification of the implant and resemble urinary calculi on CT and ultrasonography [61], 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

Surveillance and antibiotic prophylaxis — In patients treated with antibiotic prophylaxis or watchful waiting, ongoing monitoring is needed to detect recurrent urinary tract infection (UTI), to detect when and if spontaneous resolution of reflux occurs, and to assess the general health of the child [62]. Long-term follow-up is also suggested as the long-term risk of renal 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 'Prognosis and complications'.)

General evaluation includes measurements of height, weight, and blood pressure.

Mandatory urine cultures and urinalysis are required whenever there are urinary symptoms suggestive of UTI or unexplained fever. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Laboratory evaluation and diagnosis'.)

Monitoring of reflux is done by either contrast-voiding cystourethrogram (VCUG) or radionuclide cystogram (RNC). Although there is little supportive evidence for the timing of follow-up for reflux for patients on medical therapy, evaluation is typically performed in our practice every 18 to 24 months.

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

Renal ultrasound – Renal ultrasonography can be used to monitor renal growth, but fails to detect most scars, unless there is gross atrophy. A follow-up study performed several years later may be helpful to assess renal growth, especially for patients with significant scarring based on renal scan.

Dimercaptosuccinic acid (DMSA) renal scan – Guidelines from the American Urology Association (AUA) suggest that selective monitoring for renal scarring by DMSA renal scan is advised for patients at risk for significant abnormalities that may affect their care [62]. In our practice, we selectively obtain DMSA renal scans at the time of presentation in patients with grade III to V reflux with or without UTI, while others may opt to perform initial baseline scans in all children, even those with lower VUR grades (I and II). It should be noted that while less common, DMSA scan evidence of renal scarring and pyelonephritis has been found in children at presentation with grades I and II VUR [12].

For patients managed by observation alone, evidence of new scarring suggests the need for therapeutic intervention. In patients managed medically, new scarring on prophylaxis suggests that surgical correction should be considered. Follow-up DMSA renal scans can be obtained to document renal involvement after a breakthrough UTI (any UTI while on antibiotic prophylaxis). New renal scarring or evidence of pyelonephritis while on prophylaxis or surveillance without antibiotics would be a reason to suggest a change in management (eg, surgical correction or antibiotic prophylaxis for those managed by surveillance). DMSA renal scans are not routinely repeated in the absence of breakthrough infection, regardless of grade.

The Randomized Intervention for Vesicoureteral Reflux (RIVUR) trial reported significant interobserver variability in the reporting of DMSA renal scans [63].

If symptomatic breakthrough infection occurs, a change in the treatment regimen should be considered [62]. As an example, a child who is managed by observation may be changed to prophylactic antibiotics, whereas surgical correction may be considered in a child already on antibiotic prophylaxis.

Discontinuation of medical therapy — Because of the paucity of data addressing when medical therapy should be discontinued in patients initially treated with prophylactic antibiotics, indications of when to discontinue medical therapy are uncertain (see 'Discontinuation prophylactic antibiotics' above). Some experts will only discontinue therapy when the VCUG is negative. Others will discontinue therapy in older children or adolescents with grade I reflux who have been infection free for a year or so. In one author's practice (SG), discontinuation of antibiotic prophylaxis is delayed until early adolescence in patients with persistent grade I reflux. 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 [64,65].

Surgical therapy — Although some studies suggest that it is not necessary to document resolution after open surgical repair, in one author's center (SG), a postoperative VCUG or RNC is performed in patients who have undergone surgical correction to determine the success of the procedure. Both renal ultrasound and VCUG are repeated approximately six months after open surgical correction. Renal ultrasounds obtained too soon after correction demonstrate hydronephrosis that is transitory and of no clinical concern. Similarly, a renal ultrasound and VCUG are performed several months after endoscopic correction [62]. In other centers, VCUG is not performed unless there is a documented UTI following endoscopic reimplantation.

As discussed above, families whose children have undergone endoscopic therapy must be made aware of the fact that there can be later recurrence of reflux and UTIs, necessitating reimaging and possible retreatment. As a result, we perform cystograms for patients with recurrent febrile UTIs following endoscopic correction. In contrast, open surgical correction of reflux is permanent in close to 100 percent of children. Recurrent UTI in this population is much less likely to be associated with reappearance of reflux, and thus, repeat cystography is not often needed if there is one normal postoperative VCUG [66].

Long-term follow-up — Following the resolution of VUR either spontaneously or surgically, long-term follow-up should be provided for those with renal scarring. The AUA guidelines suggest annual assessments through adolescence, which include measurements of growth (height and weight) and blood pressure, and urinalysis to detect proteinuria or bacteria. Families should be made aware of the potential patient complications of hypertension and impaired renal function as well as the increased risk of VUR in first-degree relatives.

The frequency, utility, and method of detecting renal scarring have not been clearly defined. DMSA renal scan is the most sensitive measure for detecting renal scarring. Renal ultrasound is not as sensitive in detecting renal scars as DMSA scan and, as a result, has not been as useful in follow-up [67]. However, a renal ultrasound performed every two or three years may be helpful to monitor renal growth, especially for patients with significant scarring. The need for DMSA renal scan is determined on a case-by-case basis, dictated by if 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 5th to 6th 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 10th to 12th 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 e-mail 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 topics (see "Patient education: Vesicoureteral reflux in children (The Basics)")

SUMMARY AND RECOMMENDATIONS — Vesicoureteral reflux (VUR) is the retrograde passage of urine from the bladder into the upper urinary tract.

Management of VUR has been based upon the premise that VUR predisposes patients to acute pyelonephritis (upper urinary tract infection [UTI]) by allowing the transport of bacteria upward, exposing the renal parenchyma and diminishing the clearance of bacteria from the urinary tract with each void. Although data are inconclusive regarding optimal management of VUR, the approach used should fulfill the following goals (see 'Goal' above):

Prevent recurrent episodes of symptomatic UTIs or pyelonephritis

Prevent further renal damage resulting from infection and inflammation

Minimize morbidity of treatment and follow-up

Identify and manage children with bladder and bowel dysfunction (BBD) who are at-risk for recurrent pyelonephritis and VUR

BBD is a common finding in patients with VUR. Patients with VUR and BBD are at increased risk for breakthrough UTI, longer time for VUR resolution, and increased failure rate of surgical correction than patients with only VUR. As a result, we screen all patients with VUR for BBD. For patients with BBD, interventions include the use of laxatives, timed frequent voiding, pelvic floor exercises, and behavioral modification, which can both improve bladder function and lead to VUR resolution, which are discussed separately. (See 'Bladder and bowel dysfunction' above and "Management of bladder dysfunction in children".)

Therapeutic options for VUR include:

Watchful waiting consisting of a regimen of surveillance and prompt treatment of intercurrent episodes of UTI. (See 'Watchful waiting (surveillance)' above.)

Antibiotic prophylaxis to lower the risk of recurrent UTI consisting of a single daily dose of antibiotic typically given at bedtime. Antimicrobial agents most commonly used are trimethoprim-sulfamethoxazole (TMP-SMZ), TMP alone, or nitrofurantoin. (See 'Antibiotic prophylaxis' above.)

Surgical treatment correcting the anatomy at the refluxing ureterovesical junction. Surgical approaches include open surgical reimplantation, which typically requires an in-hospital admission, and ambulatory day endoscopic correction. (See 'Surgical treatment' above.)

Our management is based upon the available data and divides the choice of treatment on the severity of VUR since increasing severity of VUR is associated with increasing risk of febrile UTI recurrence and renal scarring as well as a decreased likelihood of spontaneous resolution (algorithm 1 and algorithm 2). (See 'Management' above.)

We suggest that all children with grades III through V reflux be treated (algorithm 1) (Grade 2B).We initially place all patients on prophylactic antibiotic therapy. In these patients, surgical correction is reserved for all patients with grades III to IV with breakthrough infection or who have serious adverse effects from prophylactic antibiotic therapy. In addition, surgical correction is performed in patients with persistent grade IV and V beyond two or three years of age. (See 'Grades III to V' above.)

Children with grade I to II reflux are at the lowest risk for renal scarring but remain at risk for recurrent UTI. The different treatment options of observation or antibiotic prophylaxis are presented to the family/caregivers, who play a major role in the final therapeutic decision (algorithm 2). However, we suggest prophylactic antibiotic therapy for patients with BBD as it reduces the risk of UTI (Grade 2B). We also suggest prophylactic antibiotic therapy for patients who are not toilet-trained (Grade 2C).

We do not initially recommend surgical correction in patients with low-grade reflux unless there is breakthrough UTI on medical therapy, as there is a high likelihood of spontaneous resolution (Grade 1B). (See 'Grade I and II' above.)

Patients who are treated with antibiotic prophylaxis or by "watchful waiting" require mandatory urine cultures whenever there are symptoms suggestive of UTI or unexplained fever and monitoring by repeat cystogram for the continued presence of VUR. Following a breakthrough or additional UTI, while under observation or antibiotic prophylactic management, DMSA scans can be obtained, looking for evidence of new renal scarring. These scans can be compared with any prior scans if they were performed at the time of presentation. New scarring would be compelling evidence for a change in management. (See 'Follow-up' above.)

Following surgical correction, a renal ultrasound is performed to assess for obstruction. In many centers, a cystogram may also be performed to demonstrate a successful operative outcome. In addition, reimaging should be considered in patients who undergo endoscopic correction, given the lower success rate, and certainly if there is subsequent recurrence of febrile UTIs.

Long-term follow-up includes annual assessment of linear growth, measurement of blood pressure, and urinalysis. Families should be aware of the association of VUR with increased risk of chronic kidney disease (CKD; eg, hypertension, renal impairment, or 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 an earlier version of this topic review.

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