Vesicoureteral Reflux

Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder into the upper urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. 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 Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis on prenatal ultrasonography or in a young child presenting with a urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. 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 Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. 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 Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. 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 Urinary tract infections Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections (UTIs), including pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess

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 Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis noted on prenatal ultrasound (US)
  • Postnatal period:
    • UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections (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 UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections

Imaging

Renal and bladder US:

  • Indications:
    • After 1st febrile UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections 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 Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis or renal scarring found on US 
    • 1st UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections 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 Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. 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 Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and 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 Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. 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 Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, hematuria,  UTI UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections, or failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. 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 UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections: a wide spectrum of diseases, ranging from self-limiting simple cystitis to severe pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess that can result in sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock and death. Depending on the location of the infection, patients can present with dysuria, urinary urgency, increased urinary frequency, suprapubic pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. 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 UTI Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections, diminished urinary stream, urinary incontinence Urinary incontinence Urinary incontinence (UI) is involuntary loss of bladder control or unintentional voiding, which represents a hygienic or social problem to the patient. Urinary incontinence is a symptom, a sign, and a disorder. The 5 types of UI include stress, urge, mixed, overflow, and functional. 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 Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis. The radiographic appearance of the calyces along with the normal caliber of the renal pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 "hip" bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. 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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