AUA: Vesicoureteral Reflux (2017)

See Original Guideline

See Vesicoureteral Reflux Chapter Notes

See 2017 CUA Guidelines on Antenatal Hydronephrosis

Background

• Vesicoureteral reflux (VUR) and urinary tract infections may detrimentally affect the overall health and renal function in affected children.
• VUR is diagnosed by
  1. Voiding cystourethrogram (VCUG)
  2. Radionuclide cystography

VUR Grading

Grade	Criteria
I	Reflux limited to the ureter
II	Reflux up to the renal pelvis
III	Mild dilatation of ureter and pelvicalyceal system
IV	Tortuous ureter with moderate dilatation Blunting of fornices but preserved papillary impressions
V	Tortuous ureter with severe dilatation of ureter and pelvicalyceal system Loss of fornices and papillary impressions

Diagnosis and Evaluation of a Child with VUR

UrologySchool.com Summary

• Recommended (3):
  1. History (specifically, symptoms of bladder/bowel dysfunction) + physical (specifically, height, weight, BP)
  2. Laboratory: U/A, +/- Cr if bilateral renal abnormalities
  3. Imaging: US
• Optional (2):
  1. Laboratory: Cr (in patients without bilateral renal abnormalities)
  2. Imaging: DMSA

History and Physical Exam

• History
  • Assess for symptoms of bladder/bowel dysfunction (BBD) including (6):
    1. Urinary frequency and urgency
    2. Prolonged voiding intervals
    3. Daytime wetting
    4. Perineal/penile pain
    5. Holding maneuvers (posturing to prevent wetting)
    6. Constipation/encopresis (soiling of underwear with stool by children who are beyond age of toilet training)
    • Bladder bowel dysfunction (BBD), dysfunctional voiding, dysfunctional elimination syndrome and dysfunctional lower urinary tract symptoms, refer to a common but poorly characterized complex of symptoms typically including urinary incontinence, frequency or infrequent voiding, dysuria, UTI, and constipation
    • Untreated BBD associated with:
      • Increased incidence of breakthrough UTI in children on continuous antibiotic prophylaxis (CAP)
      • Decreased resolution rates of VUR at initial follow-up in children treated with endoscopic surgery
        • BBD does not alter surgical resolution rates in children treated with open surgery
• Physical exam
  • General medical evaluation including measurement of
    • Height
    • Weight
    • Blood pressure

Labs

• Serum creatinine
  • Indications
    • Absolute (1):
      • Bilateral renal abnormalities
    • Relative
      • Children with VUR but without bilateral renal abnormalities to establish an estimate of glomerular filtration rate (GFR) for future reference.
• Urinalysis
  • Evaluate for proteinuria and bacteriuria
    • If the urinalysis indicates infection, a urine culture and sensitivity is recommended

Imaging

• Recommended (1):
  1. Renal ultrasound
     • VUR and UTI may affect renal structure and function
• Optional (1)
  1. DMSA (technetium-99m-labeled dimercaptosuccinic acid)
     • To assess the status of the kidneys for scarring and function
       • Children with higher grades of VUR (i.e. grades III to V) are at greater risk of having renal cortical abnormalities.
       • DMSA scanning can be useful to identify pre-existing abnormalities.

Initial Management of the Child with VUR

• Family and patient counseling
  • Discuss the rationale for treating VUR, the potential consequences of untreated VUR, the equivalency of certain treatment approaches,
  • Assess likely adherence with the care plan, determine parental concerns
  • Accommodate of parental preferences when treatment choices offer a similar risk-benefit balance

Goals of management (3):

1. Prevent recurring febrile UTIs
   • While resolution of VUR will reduce the incidence of febrile UTI/pyelonephritis, the overall incidence of UTI may remain unchanged
2. Prevent renal injury
   • In the setting of acute pyelonephritis, VUR significantly increases the risk of developing renal scarring
3. Minimize the morbidity of treatment and follow-up

Antibiotic prophylaxis

• RIVUR (NEJM 2014)
  • Population: 607 children with dilated and non-dilated VUR that was diagnosed after a first or second febrile or symptomatic UTI
    • Majority (91%) female population
    • Half of study participants were < 11 months of age
  • Randomized to trimethoprim-sulfamethoxazole prophylaxis vs. placebo
  • Primary outcome: recurrence of UTI
  • Results:
    • 45% significant decrease in recurrence of UTI with antibiotic prophylaxis (RR: 0.55; 95% CI: 0.38-0.78)
      • When stratified into dilated and non-dilated groups, children with dilated VUR were more likely to have symptomatic recurrences than those with non-dilated VUR
      • Prophylaxis was particularly effective in children
        1. Whose index infection was febrile
        2. Those with baseline BBD
    • No difference in the occurrence of renal scarring
  • Criticisms:
    • Population may not reflect typical patient in practice
      • Majority female and half under age 11 months
      • Trial does not address patients with VUR and no history of UTI
  • RIVUR Trial Investigators. Antimicrobial prophylaxis for children with vesicoureteral reflux. NEJM 2014; 370: 2367.

Management of VUR based on age (cut-off age 1 year)

Child age < 1 with VUR

• VUR resolution occurs in ≈50% of these children within 24 months
• Infants age < 1 may not show clinical evidence of pyelonephritis as clearly as older children and they may have a greater risk of infection-related morbidity.
• Continuous antibiotic prophylaxis (CAP)
  • Recommended in children age < 1 with (2):
    1. A history of a febrile UTI or
    2. VUR grade ≥III who is identified through screening, even in the absence of a history of febrile UTIs
  • Optional in children age < 1 with:
    • VUR grades I–II who is identified through screening, even in the absence of a history of febrile UTIs
• Circumcision
  • May be considered in the infant male with VUR based on an increased risk of UTIs in boys who are not circumcised compared to those who are circumcised.
    • Although there are insufficient data to evaluate the degree of this increased risk and its duration, parents need to be made aware of this association to permit informed decision-making.

Child age > 1 with VUR

• Recommendations are somewhat different from those age < 1, due to:
  • Greater likelihood of BBD
  • Lower probability of spontaneous resolution of VUR
  • Lower risk of acute morbidity from febrile UTI
  • Greater ability of the child to verbally complain of symptoms to indicate acute infection
• Treatment of BBD, if present, is recommended, preferably before any surgical intervention for VUR
  • There are insufficient data to recommend a specific treatment regimen for BBD
  • Treatment options for BBD (5):
    1. Behavioral therapy
    2. Biofeedback (appropriate for children age > 5)
    3. Treatment of constipation
    4. Anticholinergic medications
    5. Alpha blockers
  • Monitoring the response to BBD treatment is recommended to determine whether treatment should be maintained or modified.
• Indications for CAP in a child age > 1 year with VUR (3):
  1. BBD
  2. Recurrent febrile UTI
  3. Renal cortical abnormalities on imaging
  • In the absence of these features, CAP or observation, with prompt initiation of antibiotic therapy for UTI, are options

Follow-up of the Child with VUR not undergoing surgical intervention

• These guidelines apply to all children, irrespective of age
• Recommended follow-up:
  • Annual (3):
    1. History + Physical Exam (including monitoring of blood pressure, height, and weight)
    2. Urinalysis for proteinuria and bacteriuria; culture and sensitivity if the U/A is suggestive of infection
    3. Ultrasound to monitor renal growth and any parenchymal scarring
  • If CAP is used, voiding cystography is recommended between 12 and 24 months to determine when CAP can be stopped
    • Longer intervals between follow-up studies in recommended in patients in whom evidence supports lower rates of spontaneous resolution (i.e. those with higher grades of VUR [grades III-V], BBD, and older age)
    • If an observational approach without CAP is being used, follow-up cystography becomes an option (see below).
  • DMSA imaging [during follow-up] is recommended if:
    1. Concern for new/increased scarring (i.e. febrile UTI, high-grade VUR (grade III-V))
    2. Renal ultrasound is abnormal
    3. An elevation in serum creatinine
• Optional follow-up:
  • Follow-up cystography may be done after age >1 in patients with VUR grades I–II
    • These patients tend to have a high rate of spontaneous resolution and boys have a low risk of recurrent UTI
  • The clinical significance and the need for ongoing evaluation of grade I VUR is undefined
  • A single normal voiding cystogram (i.e. no evidence of VUR) may serve to establish resolution

Interventions for the Child with Breakthrough UTI

• If symptomatic breakthrough UTI occurs in a child with VUR receiving CAP, a change in therapy is recommended
  • The occurrence of a febrile breakthrough UTI indicates a failure of therapy and raises the concern for renal injury.
  • Symptoms of breakthrough UTI include fever, dysuria, frequency, failure to thrive, or poor feeding
    • The clinical manifestations of breakthrough UTI may not be classic, particularly in the younger child in whom systemic symptoms may predominate.
  • The specific alternative therapy should be determined based upon the individual risks to the patient, which include clinical factors such as:
    • Reflux grade
    • Degree of scarring
    • BBD
• Recommended: intervention (open surgical ureteral reimplantation or endoscopic injection of bulking agents) with curative intent in patients receiving CAP with a febrile breakthrough UTI
• Option: In patients receiving CAP with a single febrile breakthrough UTI and no evidence of renal cortical abnormalities (pre-existing or new), changing to an alternative antibiotic agent is an option prior to intervention with curative intent
• In patients not receiving CAP who develop a:
  • Febrile UTI, initiation of CAP is recommended
  • Non-febrile UTI, initiation of CAP is an option in recognition of the fact that not all cases of pyelonephritis are associated with fever

Surgical treatment of VUR

Indications (3):

1. Recurrent infections [failure of CAP or CAP not used due to patient preference]
2. New renal abnormalities on DMSA imaging
3. Parental preference

Options

1. Ureteral reimplantation
2. Endoscopic injection of bulking agents

Comparison of Options

• Ureteral reimplantation has higher resolution rates
  • Resolution rate is ≈98% for open surgery and ≈83% for endoscopic therapy after a single injection of bulking agent
• Endoscopic injection of bulking agents is less morbid
• Data demonstrating the durability of endoscopic therapy for VUR are limited
• Postoperative UTIs can occur with either treatment, but are more likely to occur in patients with a prior history of frequent UTIs

Post-operative follow-up

• Ureteral reimplantation
  • Renal US should be obtained to assess for obstruction
    • While an infrequent occurrence, urinary obstruction may be "clinically silent" and have severe consequences that could be readily corrected.
  • Voiding cystography is optional
• Endoscopic injection of bulking agents
  • Voiding cystography is recommended

Follow-up after Resolution (surgically or spontaneously) of VUR

• The long-term concerns of hypertension (particularly during pregnancy), renal functional loss, recurrent UTI, and familial VUR in the child's siblings and offspring should be discussed with the family and communicated to the child at an appropriate age.
  • The long-term health impact of VUR and renal injury may be distant in time, difficult to accurately predict, and subtle in clinical presentation. This is of particular importance in patients with renal scarring prior to reflux resolution or in whom there is a recurrence of UTI after reflux resolution.
• Following the resolution of VUR, general evaluation, including monitoring of blood pressure, height, and weight, and U/A, annually through adolescence is:
  • Recommended if either kidney is abnormal by ultrasound or DMSA scanning
  • Optional if both kidneys are normal by ultrasound or DMSA scanning
• If febrile UTI following resolution or surgical treatment of VUR, evaluate for (2):
  1. BBD
  2. Recurrent VUR

Screening for VUR

Screening in Siblings of Children with VUR

• Prevalence of VUR is 27% in siblings of children with VUR
• Goal of screening (through VCUG or radionuclide cystogram) for VUR in siblings is to identify clinically unapparent VUR in order to initiate preventative therapy, usually CAP.
  • However, the value of CAP in preventing febrile UTI and renal damage in VUR is unproven. Therefore, recommendations for screening are limited by the uncertainty of any potential benefit gained by identifying VUR.
  • Identification of VUR may be of some benefit by increasing the awareness of parents and health providers to the potentially increased risk of pyelonephritis and renal scarring
• Option: Given that the value of identifying and treating VUR is unproven, an observational approach without screening for VUR may be taken for siblings of children with VUR, with prompt treatment of any acute UTI and subsequent evaluation for VUR
• Option: Ultrasound screening of the kidneys in the sibling of a child with VUR may be performed to identify significant renal scarring and to focus attention on the presence and potential further risk of VUR
• Screening for VUR in the sibling is recommended if (2):
  1. Evidence of renal cortical abnormalities or renal size asymmetry on US [of sibling]
  2. History of UTI in the sibling who has not been tested for VUR
• Option: Sibling screening of older children who are toilet trained may be offered, although the value of identification of VUR is undefined.

Screening in Offspring

• Risk of reflux in the offspring of a patient with VUR is 36%
• Screening for VUR in the offspring is optional

Screening in the neonate with a history of prenatal hydronephrosis

• Risk of VUR in infants with prenatally detected hydronephrosis is 16%
  • Grade of hydronephrosis is NOT associated with risk of VUR
• Indications for VCUG in the neonate with a history of prenatal hydronephrosis:
  1. High-grade (SFU grade ≥3) hydronephrosis
  2. Hydroureter
  3. An abnormal bladder on ultrasound (late-term prenatal or postnatal)
  4. Develop a UTI on observation
  • There has been no demonstration of any health benefit of screening for and identifying VUR in these infants. It is therefore a recommendation that families be informed of the potential risk and permitted to participate in the decision-making.
• Option: For children with prenatally detected low-grade hydronephrosis (SFU grade 1 or 2), an observational approach without screening for VUR, with prompt treatment of any UTI, may be taken, given the unproven value of identifying and treating VUR. VCUG is also considered an option to screen for VUR.

Questions

1. What are indications for continuous antibiotic prophylaxis in children with VUR?
2. What are the treatment options for bladder bowel dysfunction?
3. Describe the follow-up of a patient with VUR?
4. What are the indications for VCUG in a neonate with antenatal hydronephrosis?

Answers

1. What are indications for continuous antibiotic prophylaxis in children with VUR?
2. What are the treatment options for bladder bowel dysfunction?
   1. Behavioral therapy
   2. Biofeedback (appropriate for children age >5)
   3. Treatment of constipation
   4. Anti-cholinergic medications
   5. Alpha blockers
3. Describe the follow-up of a patient with VUR?
   1. Annual history and physical exam (including measurement of blood pressure, height, and weight)
   2. Urinalysis
   3. Ultrasound
   4. If continuous antibiotic prophylaxis used, then VCUG between 12 and 24 months
4. What are the indications for VCUG in a neonate with antenatal hydronephrosis?

References

1. Peters, Craig A., et al. "Summary of the AUA guideline on management of primary vesicoureteral reflux in children." The Journal of urology 184.3 (2010): 1134-1144.