Vesicoureteral Reflux

Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the upper urinary tract. Primary VUR often results from the incomplete closure of the ureterovesical junction, whereas secondary VUR is due to an anatomic or physiologic obstruction. Vesicoureteral reflux does not cause specific symptoms, but it is suspected after detecting hydronephrosis on prenatal ultrasonography or in a young child presenting with a urinary tract infection. A voiding cystourethrogram should be performed to diagnose the condition and assess its severity. The majority of patients will have spontaneous resolution of VUR. Some patients may require surgical management, particularly individuals with high-grade reflux.

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Overview

Definition

Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the upper urinary tract.

Epidemiology

  • The most common urinary finding in children:
    • Occurs in 1%–2% of children < 2 years of age
    • Prevalence is 15% in children with prenatal hydronephrosis
  • 3 times more common in white children than Black children
  • 2 times more common in girls than boys

Etiology

Primary VUR:

  • Genetic predisposition
  • Congenital defect of the terminal portion of the ureter (e.g., short intravesical ureter)

Secondary VUR:

  • Anatomic causes:
    • Posterior urethral valves
    • Congenital ureteral duplication
    • Bladder outlet obstruction
  • Functional bladder obstruction:
    • Neurogenic bladder (e.g., spina bifida)
    • Detrusor instability

Pathophysiology

Normal physiology

  • The distal ureters course through the bladder wall at an oblique angle.
  • During micturition, the bladder and the surrounding muscles contract and compress the intravesical ureter → prevention of urine reflux into the ureters
The normal function of the bladder and ureteres

Normal function of the bladder and ureters:
The ureters enter at an angle, allowing the bladder to squeeze the ureteral opening, which is closed during micturition to prevent reflux.

Image by Lecturio.

Primary VUR

  • A short intravesical ureter → ureter enters at a different angle
  • Malfunction of the valve-like mechanism during micturition → reflux of urine into the ureter and collecting system
The pathophysiology of primary vesicoureteral reflux

Pathophysiology of primary vesicoureteral reflux:
A defect in the terminal ureter and in the ability to close the ureterovesicular junction results in the antegrade flow up the ureters during micturition.

Image by Lecturio.

Potential consequences

  • Persistent intrarenal reflux → renal scarring → reflux nephropathy
  • VUR → ↑ risk of urinary tract infections (UTIs), including pyelonephritis

Clinical Presentation and Diagnosis

Clinical presentation

There are no specific signs or symptoms for VUR, and the condition may be suspected in the following circumstances:

  • Prenatal period: hydronephrosis noted on prenatal ultrasound (US)
  • Postnatal period:
    • UTI (often recurrent)
    • Bowel or bladder dysfunction

Supporting laboratory evaluation

There are no laboratory tests that can diagnose VUR. The following assessments may be performed to evaluate for complications:

  • BUN and creatinine → renal dysfunction
  • Urinalysis with culture → UTI

Imaging

Renal and bladder US:

  • Indications:
    • After 1st febrile UTI in all children aged 2–24 months
    • In all children with recurrent cases of UTIs
  • Potential findings:
    • Dilated ureters
    • Hydronephrosis

Voiding cystourethrogram:

  • Test of choice for the diagnosis and degree of VUR
  • Indications:
    • Bilateral hydronephrosis or renal scarring found on US 
    • 1st UTI with abnormal US
    • Recurrent UTIs
  • Technique:
    • Contrast is placed in the bladder through a catheter. 
    • Fluoroscopy images are taken during voiding.
    • Reflux of contrast into the ureter during voiding → VUR
Imaging findings in vesicoureteral reflux

Imaging findings in vesicoureteral reflux:
A: Postnatal ultrasound showing unilateral hydronephrosis
B: Voiding cystourethrogram showing contrast reflux in the right and left ureters and collecting systems (right: grade III, left: grade V)

Image: “Imaging findings in vesicoureteral reflux” by Department of Urology, Kles Kidney Foundation, Nehru Nagar, Belgaum, India. License: CC BY 2.0

Severity classification

Severity classification helps grade the severity of VUR based on imaging findings.

  • Grade I: reflux into the ureter
  • Grade II: reflux into the entirety of the ureter
  • Grade III: Reflux fills and mildly dilates the ureter with mild blunting of the calyces.
  • Grade IV: Reflux results in grossly dilated ureters and calyces. Some tortuosity of the ureter is also seen.
  • Grade V: massive reflux causing significant dilation of the urinary collecting system and intrarenal reflux (“megaureter”)
Vesicoureteral reflux classification

Severity classification of vesicoureteral reflux

Image by Lecturio.

Management and Prognosis

Management

Conservative management:

  • Surveillance:
    • Most cases resolve spontaneously.
    • Appropriate for grades I and II
  • Prompt treatment of UTIs
  • Antibiotic prophylaxis:
    • Controversial 
    • The goal is to prevent recurrent UTIs.
    • Options:
      • Trimethoprim-sulfamethoxazole
      • Nitrofurantoin

Invasive management:

  • Goal is to improve the angle of the ureter → ↓ reflux
  • Indications:
    • Grades IV or V
    • Recurrent UTIs despite antibiotic prophylaxis
    • Declining renal function
  • Procedures:
    • Subureteric transurethral injection
    • Open surgical reimplantation of ureters

Prognosis

  • Most patients show spontaneous resolution of VUR.
  • Factors that increase the likelihood of resolution:
    • Lower severity of reflux
    • Age of diagnosis < 2 years
    • Unilateral disease

Differential Diagnosis

  • Ureteropelvic junction obstruction: the most common cause of pediatric hydronephrosis. An anatomic lesion or functional disturbance causes an obstruction where the ureter enters the kidney. Ureteropelvic junction obstruction usually presents as a palpable abdominal mass, flank pain, hematuria, UTI, or failure to thrive. The diagnosis is made with imaging. A voiding cystourethrogram should be performed to rule out VUR. Management may include surveillance or surgery.
  • UTI: a wide spectrum of diseases, ranging from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Depending on the location of the infection, patients can present with dysuria, urinary urgency, increased urinary frequency, suprapubic pain, and fever. Urinalysis and urine culture along with the clinical presentation help in the diagnosis of UTIs. Imaging should be ordered to rule out VUR in children. Management options include oral or IV antibiotics.
  • Posterior urethral valves: obstructing membranous folds within the lumen of the posterior urethra. Infants usually present with UTI, diminished urinary stream, urinary incontinence, and VUR. The diagnosis of posterior urethral valves can be made using US or a voiding cystourethrogram. Management is with surgery.
  • Congenital megacalyces: an incidental finding resulting from the underdevelopment of the renal medullary pyramids. The resulting enlargement of the calyces can mimic hydronephrosis. The radiographic appearance of the calyces along with the normal caliber of the renal pelvis and ureter aid in the diagnosis. No management is required.

References

  1. Baskin, L.S. (2020). Congenital ureteropelvic junction obstruction. UpToDate. Retrieved March 12, 2021, from https://www.uptodate.com/contents/congenital-ureteropelvic-junction-obstruction
  2. Holmes, N. (2020). Clinical presentation and diagnosis of posterior urethral valves. UpToDate. Retrieved March 12, 2021, from https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-posterior-urethral-valves
  3. Mattoo, T.K., Greenfield, S.P. (2021). Clinical presentation, diagnosis, and course of primary vesicoureteral reflux. UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/clinical-presentation-diagnosis-and-course-of-primary-vesicoureteral-reflux
  4. Mattoo, T.K., Greenfield, S.P. (2021). Management of vesicoureteral reflux. In Kim, M.S. (Ed.), UpToDate. Retrieved April 25, 2021, from https://www.uptodate.com/contents/management-of-vesicoureteral-reflux
  5. Van Why, S.K., Avner, E.D. (2016). Vesicoureteral Reflux. Nelson Textbook of Pediatrics, 2562–67.
  6. Estrada, Jr., C.R., Cendron, M. (2018). Vesicoureteral reflux. In Kim, E.D. (Ed.), Medscape. Retrieved April 25, 2021, from https://emedicine.medscape.com/article/439403-overview
  7. Banker, H., Aeddula, N.R. (2020). Vesicoureteral reflux. [online] StatPearls. Retrieved April 25, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK563262/

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