Vesicoureteral reflux

Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the ureter. Primary VUR is the most common type and is due to a developmental anomaly of the vesicoureteric junction (VUJ). Secondary VUR is caused by bladder outlet obstruction, congenital ureteral anomalies, or voiding dysfunction (e.g., neurogenic bladder). Children with VUR are usually asymptomatic or may present with a febrile urinary tract infection (UTI). Other manifestations include hypertension, uremia, and kidney failure in advanced cases of reflux nephropathy. VUR is diagnosed based on voiding cystourethrography findings. Treatment includes surveillance, continuous antibiotic prophylaxis, and/or surgery and is based on VUR grade, risk for kidney injury, and likelihood of spontaneous resolution. Children with VUR often have associated bladder and bowel dysfunction (BBD), which decreases the likelihood of spontaneous resolution and should be assessed for and treated. Complications of VUR include hydronephrosis, pyelonephritis, and chronic kidney disease (CKD).

• Prevalence
  • ∼ 2 % of all newborns
  • Approx. 40% of children with a UTI
  • Approx. 15% of infants with antenatally diagnosed hydronephrosis ^[1][2]
  • Prevalence decreases with age. ^[3]
• Peak incidence: children < 2 years of age ^[4]
• Sex
  • ♂ > ♀ in children < 2 years of age
  • ♀ > ♂ in older children
• Race: more common in White children than Black children

Epidemiological data refers to the US, unless otherwise specified.

Primary VUR (most common type)

• Developmental anomaly of the vesicoureteric junction (VUJ): short intramural ureter → VUJ fails to close completely during bladder contraction → VUR
• A hereditary component is likely. ^[5]

Secondary VUR ^[5]

• Bladder outlet obstruction: high pressure within the bladder → reflux of urine through the VUJ
  • Anatomical (e.g., posterior urethral valves, urethral meatal stenosis)
  • Functional (e.g., neurogenic bladder)
• Congenital anomalies of the ureter
  • Duplex collecting system: most common congenital renal abnormality (affects ∼ 1% of the population) ^[6]
  • Ectopic ureter
  • Ureterocele
• Iatrogenic: following surgery that involves the vesical trigone (e.g., transurethral bladder operations); renal transplant surgery ^[7][8]

• Suspected in the prenatal period when hydronephrosis is detected on routine antenatal ultrasound
• Postnatal presentation
  • Recurrent febrile urinary tract infections
    • Neonates: irritability, fever
    • Older children: urinary urgency, frequency, incontinence, and dysuria associated with fever
    • See also "Clinical features of UTI in children."
  • Reflux nephropathy
  • Flank or abdominal pain before or during voiding

VUR is generally asymptomatic until it causes a urinary tract infection.

General principles ^[5][9][10]

• VUR is typically diagnosed through either of the following:
  • Diagnostics for pediatric UTI
  • Follow-up of antenatally detected hydronephrosis
• Imaging is necessary to confirm diagnosis of VUR.
  • Renal and bladder ultrasound (RBUS) is typically performed as initial imaging to assess for structural abnormalities, but it is not diagnostic.
  • Voiding cystourethrography (VCUG) is the gold standard for diagnosis. ^[1][5]
• Laboratory studies and additional imaging are indicated to assess for:
  • Complications (e.g., UTI, kidney failure)
  • An underlying cause and/or associated BBD

Imaging

RBUS ^[9][10][11]

• Indications
  • Selected patients with UTI: See "Imaging for pediatric UTI." ^[9][10]
  • Postnatal follow-up of antenatally detected urinary tract dilation ^[1]
• Findings suggestive of VUR include: ^[5]
  • Hydronephrosis
  • Ureteral dilation
  • Changes to the renal parenchyma
  • Asymmetric kidney size
  • Bladder abnormalities (e.g., bladder wall thickening)
  • Congenital anomalies (e.g., duplex kidney)

RBUS has low sensitivity and specificity for detecting VUR. Normal findings on RBUS do not rule out VUR. ^[11]

VUR imaging ^[1][5]

• Indications ^[10][11]
  • Findings suggestive of VUR on RBUS
  • Any of the following (regardless of RBUS findings)
    • Atypical or complicated pediatric UTI
    • Recurrent febrile UTI
• Modalities
  • VCUG: gold standard ^[1][5]
  • Voiding urosonography: a radiation-free alternative to VCUG that uses a microbubble contrast to evaluate for VUR and associated renal anomalies ^[9][10]
  • Radionuclide cystography: uses a radioactive tracer (e.g., Tc-99m MAG3) to evaluate for VUR ^[12]
    • May be considered as an alternative to VCUG in girls ^[9]
    • Toilet-trained children may not require catheterization.
• Findings ^[10]
  • Retrograde flow of contrast into the ureters
  • Visualization of urinary tract dilation and congenital anomalies of the urinary tract
  • See also "VUR grading".

Other imaging

• DMSA scan: may be considered in selected patients to assess kidney function and evaluate for renal scarring ^[10][11]
• Urodynamic testing: may be used to evaluate patients with secondary VUR ^[5]

Laboratory studies ^[5]

Indicated in all patients as part of the initial assessment.

• Urinalysis and urine culture: to evaluate for pediatric UTI
• Kidney function tests: to assess for kidney disease

Vesicoureteral reflux is graded from I–V using the grading system from the International Reflux Study. Higher grades represent more severe disease. ^[5][13][14]

The goal of VUR management is to prevent complications (e.g., recurrent febrile UTI, reflux nephropathy).

Approach ^[5]

• All patients
  • Refer patients to specialists (e.g., urology) for management.
  • Identify and treat associated complications, e.g.:
    • UTI
    • Hypertension
    • Proteinuria
  • For secondary VUR, treat the underlying cause.
• Children
  • Choice of management depends on several factors, including the likelihood of spontaneous resolution and patient and/or family preference. ^[5]
  • VUR grades I and II without complications: typically managed with surveillance or continuous antibiotic prophylaxis
  • VUR grade ≥ 4 and/or complications: Surgery may be indicated.
• Adults ^[3]
  • There is insufficient evidence on management of VUR in adults.
  • Surgery may be considered for adults with VUR and recurrent UTIs and/or pyelonephritis.

VUR often resolves spontaneously, especially in children with primary VUR grades I or II. ^[5]

There is insufficient evidence to recommend routine screening of asymptomatic family members of patients with VUR. Educate family members on the increased risk for VUR and the need for prompt evaluation of UTI symptoms. ^[5]

Conservative management ^[5]

Surveillance

• Surveillance alone may be considered in children with lower grade VUR, low risk for recurrent febrile UTIs, and no known renal scarring.
• Educate caregivers on the symptoms of pediatric UTI and need for prompt treatment of pediatric UTI.
• Identify and treat BBD: voiding behavior modification, treatment of pediatric constipation
• Circumcision of male infants with VUR may be considered to decrease the risk of UTIs; use shared decision-making. ^[5]
• Serially monitor the following to assess for complications and disease status: ^[5]
  • Weight and height
  • Blood pressure
  • Kidney function tests
  • Imaging, e.g.: ^[9]
    • RBUS to assess kidney growth and scarring
    • VUR imaging for progression or resolution of VUR
    • DMSA scan as indicated for follow-up of abnormal imaging findings or other concerns for scarring

Up to 50% of infants and children with VUR have BBD, which increases the risk for complications and decreases the likelihood of spontaneous resolution of VUR.

Continuous antibiotic prophylaxis

• In addition to surveillance, consider continuous antibiotic prophylaxis in: ^[5]
  • Children < 1 year of age
  • Children with VUR grade IV or V and/or risk factors for pediatric UTI ^[5]
  • Children with febrile UTI during surveillance
• Options: low-dose trimethoprim/sulfamethoxazole, amoxicillin, nitrofurantoin ^[5]
• Duration: tailored to the individual ^[5]

Surgery

• Indications ^[5]
  • Persistent grade IV or V VUR ^[5]
  • Breakthrough febrile UTIs despite continuous antibiotic prophylaxis
  • Noncompliance with long-term prophylactic antibiotics
  • New renal scarring
  • Patient and/or family preference
• Options ^[5]
  • Endoscopic subureteric transurethral injection ^[5]
  • Ureteroneocystostomy (ureteral reimplantation) ^[5]

After surgery, follow up with patients through adolescence to evaluate for complications of VUR and assess kidney function. ^[5]

Treat BBD (voiding behavior modification, treatment of constipation) and monitor for resolution of VUR before considering surgical management of VUR.

• Infections ^[5]
  • Urosepsis
  • Pyelonephritis
  • Perinephric abscess
• Renal complications ^[5]
  • Megaureter
  • Hydronephrosis
  • Reflux nephropathy: renal scarring due to VUR ^[15]
    • Patients are often asymptomatic.
    • Can lead to hypertension, chronic kidney disease and, rarely, end-stage kidney disease ^[16]

We list the most important complications. The selection is not exhaustive.