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 congenital defect of the terminal portion of the ureter. Bladder outlet obstruction, cystitis, and congenital ureteral anomalies (e.g., ureteral duplication, ectopic ureter) may cause secondary VUR. Children with VUR are usually asymptomatic until they develop a urinary tract infection (presenting with fever, dysuria, urgency, flank pain). Other manifestations include hypertension, uremia, and kidney failure in advanced cases of reflux nephropathy. The initial workup for VUR includes laboratory tests (creatinine levels, electrolytes) and renal ultrasound for evaluation of kidney function and possible structural damage. Voiding cystourethrogram is the diagnostic test of choice for demonstrating urinary reflux and the severity of the disease. Most cases of primary VUR resolve spontaneously as the child ages. Medical management with prophylactic antibiotics (e.g., trimethoprim-sulfamethoxazole, nitrofurantoin) and behavioral modification (timed micturition) has proven successful in treating and preventing complications. Patients with higher grades of primary VUR with ureteral dilation and hydronephrosis or with recurrent UTIs require endoscopic/surgical correction of the vesicoureteral junction. Treatment of the underlying cause corrects secondary VUR. Complications of VUR include hydronephrosis, obstructive nephropathy, pyelonephritis, and chronic kidney disease.

• Incidence: ∼ 1% of newborns ^[1]
• Age: : children < 2 years ^[2]
• Sex: ♀ > ♂ (2:1) ^[2]
• Race: more common in white children ^[2]

Epidemiological data refers to the US, unless otherwise specified.

Primary VUR (most common type) ^[3]

• Short intramural ureter → vesicoureteric junction (VUJ) fails to close completely during bladder contraction → VUR

Secondary VUR

• Bladder outlet obstruction (anatomic/functional): high pressure within the bladder → reflux of urine through the VUJ
  • Anatomic: posterior urethral valves; ; urethral meatal stenosis
  • Functional: bladder and bowel dysfunction ; neurogenic bladder ^[4]
  • Cystitis
• Congenital anomalies of the ureter
  • Ureteral duplication (most common renal abnormality; 1% of the population)
  • Ectopic ureter
  • Ureterocele
• Iatrogenic

• Suspected in the prenatal period when hydronephrosis is detected on routine antenatal ultrasound
• Postnatal presentation
  • Recurrent febrile urinary tract infections
    • Neonates: irritability, fever, and listlessness
    • Older children: urinary urgency, frequency, incontinence, and dysuria associated with fever
  • Reflux nephropathy : renovascular hypertension, kidney failure, uremia ^[5]
  • Flank or abdominal pain before or during voiding

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

Laboratory studies

• Urinalysis and urine culture: indicated in all children with hydronephrosis to rule out infection
• Renal function tests: serum creatinine, urea, and electrolytes

Imaging

Ultrasound

• Indicated in children with febrile UTI and for follow-ups
• Detection of hydronephrosis and dilated ureter

Contrast voiding cystourethrogram (micturating cystourethrogram)

• Indications
  • Children with ≥ 2 episodes of febrile UTIs or
  • First febrile UTI in a child and any of the following:
  • A renal anomaly detected on ultrasound
  • Fever ≥ 39°C (102.2°F) and a pathogen other than E. coli detected in urine culture
  • Hypertension
• Procedure: Contrast is instilled into the bladder through a urethral catheter; images are obtained via fluoroscopy while the child is voiding.
• Findings: Retrograde reflux of the contrast into the ureters during micturition is diagnostic of VUR.
• Grading: VUR is divided into 5 grades of severity based on the results of the voiding cystourethrogram.

DMSA renal scan ^[7]

• Nuclear imaging method based on the injection of radioactive dimercaptosuccinic acid
• Assessment of cortical tissue, renal function, and scarring (indicated in the case of hypodense photopenic lesions)
• Further indicated for follow-ups and treatment monitoring

MAG3 scan (radionuclear cystourethrography)

• A nuclear medicine scan using the radiolabelled isotope MAG3 (mercaptoacetyltriglycine)
• Detects VUR, especially if caused by obstructions , measures renal function
• Follow-ups

Urodynamic testing

• Indicated in the evaluation of secondary VUR

Conservative treatment

• Indications: VUR grades I–III in children < 5 years of age ^[8][9]
• Long-term prophylactic antibiotics
  • Children > 3 months: trimethoprim-sulfamethoxazole, nitrofurantoin
  • Infants < 2 months: amoxicillin
• Correction of voiding dysfunction: behavior modification (e.g., timed voiding (every 3 hours), prevention of constipation)
• Close surveillance: urinalysis, renal imaging ^[10]

Surgical treatment

• Indications
  • VUR ≥ grade IV
  • Bilateral grade III VUR, especially in children > 6 years
  • Worsening renal function/breakthrough urinary tract infections despite prophylactic antibiotics
• Subureteric transurethral injection (STING procedure) ^[11]
  • Cystoscopy-guided injection of dextranomer/hyaluronic acid below the mucosa of the ureterovesical junction keeps the intravesical ureter in place, alters its angle, and, thereby, corrects the VUR.
  • Day-care procedure
  • Success rates of up to 90%
• Surgery: ureteral reimplantation (ureteroneocystostomy)

• Infections
  • Urosepsis
  • Pyelonephritis
  • Perinephric abscess
• Renal complications
  • Megaureter
  • Hydronephrosis
  • Renal scarring
  • Chronic kidney disease

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