Residency · Residency · Urology

Vesicoureteral Reflux: Evaluation and Management

Definition and Epidemiology

Vesicoureteral reflux (VUR) is characterized by the backward flow of urine from the bladder into the ureter and potentially up to the kidney. It affects approximately 1% of the general pediatric population but is found in 30-50% of children who present with febrile urinary tract infections (UTIs). Clinically, females are more frequently diagnosed due to their higher incidence of UTIs, whereas males are more commonly identified prenatally. The prevalence among siblings of affected children is significant, ranging from 27-32%, which supports screening recommendations for siblings. Additionally, if a parent has VUR, the risk to offspring rises to about 66%. Most cases of primary VUR tend to resolve spontaneously as the child grows.

Pathophysiology

Normal Antireflux Mechanism

Under normal conditions, the ureter enters the bladder at an oblique angle through the detrusor muscle hiatus. This anatomical arrangement creates an intramural ureteral tunnel with a length-to-diameter ratio of approximately 5:1, which functions as a passive valve to prevent reflux. As the bladder fills and intravesical pressure rises, this pressure compresses the intramural tunnel, effectively closing it off and stopping urine from flowing backward. Additional support is provided by the Waldeyer sheath and the trigonal musculature, reinforcing the valve mechanism.

Primary VUR

Primary VUR arises from a congenital defect in this antireflux mechanism, specifically a deficiency in the intramural tunnel. This may manifest as a shortened tunnel or lateral displacement (ectopia) of the ureteral orifice. The morphology of the ureteral orifice correlates with the severity of reflux: a normal cone-shaped orifice is associated with no reflux, while abnormal shapes such as stadium, horseshoe, or golf-hole configurations correspond to increasing reflux grades. As the bladder grows and the intramural tunnel lengthens with maturation, many cases of primary VUR resolve spontaneously. The likelihood of resolution depends on factors such as reflux grade, patient age, whether reflux is unilateral or bilateral, and sex.

Secondary VUR

Secondary VUR results from elevated intravesical pressure or anatomical obstruction. Common causes include posterior urethral valves, neurogenic bladder, bladder dysfunctions such as dysfunctional voiding or overactive bladder, and prior surgical interventions. In these cases, identifying and treating the underlying cause is essential to managing reflux effectively.

<image>Cross-sectional anatomy of the normal ureterovesical junction showing the oblique intramural tunnel and valve mechanism, compared with a deficient tunnel in primary VUR</image>

Grading System (International Reflux Study Classification)

The International Reflux Study classification grades VUR from I to V based on the extent of reflux and dilation. Grade I involves reflux into a non-dilated ureter only. Grade II includes reflux into the ureter and collecting system without dilation, with normal calyces. Grade III shows mild to moderate dilation of the ureter and renal pelvis, with mild blunting of the calyces. Grade IV is characterized by moderate dilation with complete obliteration of calyceal angles, although papillary impressions remain visible. Grade V represents gross dilation and tortuosity of the ureter, loss of papillary impressions, and intrarenal reflux.

Evaluation

Voiding Cystourethrogram (VCUG)

The VCUG is the gold standard for diagnosing and grading VUR. This fluoroscopic study involves catheterization of the bladder and instillation of contrast material, with imaging performed during bladder filling and voiding phases. It allows visualization of reflux grade, bladder morphology including trabeculation and diverticula, and detection of posterior urethral valves in males. Cyclic VCUG, which involves multiple fill and void cycles, increases sensitivity for detecting reflux. Typically, the VCUG is performed 4-6 weeks after UTI treatment, although earlier timing is acceptable in some cases.

Radionuclide Cystogram (RNC)

The radionuclide cystogram uses technetium-99m instilled via catheter and provides continuous monitoring, resulting in higher sensitivity for detecting reflux compared to VCUG. It exposes the patient to lower radiation but cannot precisely grade reflux or assess bladder and urethral anatomy. Therefore, RNC is best suited for follow-up surveillance and screening of siblings.

DMSA Renal Scan

The DMSA renal scan is the gold standard for detecting renal cortical scarring. It identifies focal cortical defects indicative of scarring and assesses differential renal function. Acute DMSA scans can detect pyelonephritis by revealing photopenic areas corresponding to inflammation, while chronic scars represent permanent damage, often located at the upper or lower poles of the kidney. This scan is crucial for prognosis and guiding surgical decisions.

Renal Ultrasound

Renal ultrasound serves as an initial screening tool to detect hydronephrosis, asymmetry in renal size, cortical thinning, and ureteral dilation. However, it cannot diagnose or grade VUR, and a normal ultrasound does not exclude the presence of reflux. Ultrasound remains useful for ongoing monitoring.

Voiding Assessment

Assessment of voiding function is essential in all patients with VUR because dysfunctional voiding can worsen reflux and hinder its resolution. Evaluation includes screening for bladder bowel dysfunction (BBD), which encompasses constipation, encopresis, urinary frequency, urgency, and incontinence, as well as dysfunctional voiding characterized by incomplete relaxation of the pelvic floor during urination. Uroflowmetry combined with electromyography (EMG) is recommended in toilet-trained children. BBD is the strongest predictor of persistent VUR and breakthrough UTIs.

<image>VCUG images demonstrating grades I through V vesicoureteral reflux, showing progressive ureteral and collecting system dilation</image>

Natural History and Spontaneous Resolution

The overall spontaneous resolution rate for VUR is approximately 80% for grades I and II, around 50% for grade III, and less than 30% for grades IV and V. Factors that favor spontaneous resolution include lower reflux grade (I-III), unilateral reflux, younger age at diagnosis, female sex, absence of renal scarring, and absence of BBD. The annual resolution rate for lower grades is about 10-15%. Resolution becomes unlikely if reflux persists beyond 10-12 years of age or if high-grade reflux is present.

Management Options

Observation Alone

Observation without intervention is appropriate for patients with low-grade VUR (grades I-II) who have not experienced febrile UTIs, as well as those with prenatal hydronephrosis and VUR but no history of UTI. These patients should be monitored with renal ultrasound and clinical follow-up, with prompt treatment of any UTIs.

Continuous Antibiotic Prophylaxis (CAP)

Continuous antibiotic prophylaxis has historically been the mainstay of VUR management, aiming to prevent UTIs while awaiting spontaneous resolution. Common regimens include trimethoprim-sulfamethoxazole (TMP-SMX) at 2 mg/kg of trimethoprim given at bedtime for children older than two months, nitrofurantoin at 1-2 mg/kg at bedtime for children older than one month, and amoxicillin at 10 mg/kg at bedtime for neonates and infants younger than two months. CAP is continued until reflux resolves or surgical intervention is undertaken. The RIVUR Trial demonstrated that CAP with TMP-SMX reduces UTI recurrence by 50% compared to placebo in children with VUR grades I-IV, with a number needed to treat of eight to prevent one UTI over two years. However, CAP did not reduce renal scarring. Limitations of CAP include concerns about antibiotic resistance, compliance challenges, and side effects. The American Urological Association (AUA) recommends CAP for patients with grades I-IV VUR who experience breakthrough febrile UTIs.

Bladder Bowel Dysfunction Management

Management of bladder bowel dysfunction is a critical adjunct to any VUR treatment strategy. Aggressive treatment of constipation using agents such as polyethylene glycol (Miralax), dietary fiber, and adequate hydration is essential. Timed voiding every two to three hours and biofeedback therapy for dysfunctional voiding are also important. Successful resolution of BBD improves rates of VUR resolution and reduces UTI recurrence. Current VUR-specific guidelines mandate assessment and treatment of BBD.

Endoscopic Injection (STING/HIT Procedure)

Endoscopic injection using Deflux, a dextranomer/hyaluronic acid copolymer, is the most commonly used bulking agent to recreate the valve mechanism at the ureteral orifice. The STING procedure involves a single subureteric injection beneath the ureteral orifice. The HIT (hydrodistention-implantation technique) involves injecting within the ureteral tunnel under hydrodistention, and the Double-HIT technique combines intraorifice and submucosal injections for improved outcomes. These outpatient procedures have minimal morbidity. Success rates for a single injection vary by reflux grade: 80-90% for grades I-II, 70-80% for grade III, 50-60% for grade IV, and less than 50% for grade V. Repeat injections can improve cumulative success rates. However, endoscopic injection has lower durability than surgical reimplantation, with a 10-20% recurrence rate, making it less ideal for high-grade reflux.

Surgical Reimplantation (Ureteral Reimplant)

Open Reimplantation

Open ureteral reimplantation remains the gold standard for definitive correction of VUR, with success rates between 95-99% regardless of reflux grade. The most common approach is the intravesical Cohen cross-trigonal technique, which tunnels the ureter across the trigone beneath the bladder mucosa. This method offers a high success rate but alters the ureteral orifice position, complicating future retrograde ureteral access such as stenting or ureteroscopy. The Politano-Leadbetter intravesical approach tunnels the ureter from a new hiatus superolaterally to an orifice near its normal position, preserving orifice location but carrying a higher complication risk, including ureteral kinking. The extravesical Lich-Gregoir approach creates a detrusor tunnel without opening the bladder, allowing faster recovery, no hematuria, and no bladder spasms. However, bilateral extravesical reimplantation may cause transient urinary retention in 5-10% of cases, so some surgeons avoid simultaneous bilateral procedures. This approach is increasingly favored for unilateral reflux.

Robotic-Assisted Reimplantation

Robotic-assisted reimplantation most commonly employs the extravesical Lich-Gregoir technique. Although an intravesical robotic approach has been described, it is technically demanding. Robotic surgery is gaining popularity, with outcomes approaching those of open surgery in experienced centers. Advantages include improved cosmesis and potentially shorter hospital stays, while disadvantages include longer operative times, higher costs, and a learning curve.

<image>Surgical diagrams comparing Cohen cross-trigonal reimplantation (intravesical), Politano-Leadbetter reimplantation, and Lich-Gregoir extravesical reimplantation techniques</image>

Indications for Surgical Intervention

Surgical intervention is indicated in cases of breakthrough febrile UTIs despite CAP, high-grade VUR (grades IV-V) unlikely to resolve spontaneously, renal scarring on DMSA scan with ongoing reflux, persistent VUR beyond an appropriate observation period, poor compliance with CAP or parental preference for surgery, non-resolution of reflux despite treatment of concurrent BBD, and VUR associated with anatomic abnormalities such as ureteral duplication or ureterocele.

Screening Recommendations

Screening is recommended for siblings of affected children due to a 27-32% prevalence of VUR, with the AUA advising screening for siblings under one year of age who have prenatal hydronephrosis or a history of UTI. The screening of asymptomatic siblings remains debated. Offspring of affected parents have a higher risk (66%) and should be screened if symptomatic. Children with prenatal hydronephrosis should undergo VCUG if postnatal hydronephrosis persists or if a UTI occurs.

Complications of VUR

Complications of VUR include reflux nephropathy, which is chronic pyelonephritis with scarring that can lead to chronic kidney disease (CKD). Historically, reflux nephropathy was a leading cause of pediatric end-stage renal disease (ESRD), although early diagnosis has reduced this incidence. Bilateral scarring increases the risk of hypertension. Recurrent febrile UTIs pose a risk of sepsis, and chronic infection and CKD can contribute to growth retardation.

Clinical Pearls

Bladder bowel dysfunction is the most important modifiable factor in managing VUR; therefore, assessment and treatment of constipation and dysfunctional voiding should always precede or accompany any VUR-specific intervention. The RIVUR trial demonstrated that continuous antibiotic prophylaxis reduces UTIs by 50% but does not prevent renal scarring, highlighting that the primary benefit of prophylaxis is UTI prevention rather than long-term renal protection. Open ureteral reimplantation remains the gold standard with a 95-99% success rate regardless of reflux grade, while Deflux injection is less durable, achieving 75-85% overall success but is less invasive. The Cohen cross-trigonal technique is the most commonly used open surgical method; however, it redirects the ureteral orifice, complicating future retrograde access such as stenting or ureteroscopy. It is essential to obtain a VCUG, not just a renal ultrasound, to diagnose and grade VUR, as a normal ultrasound does not exclude reflux. Most low-grade VUR (grades I-III) resolves spontaneously, and the clinical challenge lies in identifying which patients require intervention versus observation.

References

• AUA Guideline on Management of Primary VUR in Children, 2010 (amended 2017)
• EAU/ESPU Guidelines on Vesicoureteral Reflux, 2024 Update
• RIVUR Trial Investigators. "Antimicrobial prophylaxis for children with vesicoureteral reflux." NEJM. 2014;370(25):2367-2376.
• Kirsch AJ, et al. "The modified STING procedure for correction of VUR." J Urol. 2004;171(6 Pt 1):2413-2416.
• Elder JS, et al. "Management of VUR in children." AUA Update Series. 2018.
• Campbell-Walsh-Wein Urology, 12th Edition, Chapter on Vesicoureteral Reflux

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