Pediatrics: Posterior Urethral Valves & Other Urethral Anomalies

Posterior Urethral Valves (PUV)

Background

• Most common cause of bladder outlet obstruction in infants
  • In females, anatomic bladder obstruction is rare. The most common structural obstruction in females is from a ureterocele that prolapses into the bladder neck.
• Classification
  • Type 1 valves
    • Most common variant
    • Appear as leaflets that arise from the verumontanum and fuse anteriorly just proximal to the external urethral sphincter
  • Type 3 valves
    • Present as a congenitally obstructing membrane that is likely perforated at the time of the initial postnatal catheterization

Epidemiology

• Incidence: 1.6-2.1 per 10,000 births

Pathophysiology

• Downstream consequences of PUV
  1. Lung
     • Pulmonary hypoplasia
       • Most profound complication and cause of perinatal mortality in infants affected by severe lower urinary tract obstruction due to a noncompliant and hypoplastic lung.
       • Limited data on long-term natural history of survivors
  2. Kidney
     • Glomerular injury
       • Due to
         • Obstructive uropathy
           • Reversible renal insufficiency; usually improves with initial treatment but can recur with bladder dysfunction
         • Dysplasia
           • Irreversible renal insufficiency; permanent level of renal damage that limits growth; leads to progressive renal failure and hypertension
     • Tubular injury
       • Inability to limit sodium and water loss
         • Progressive with age
         • Can result in nephrogenic diabetes insipidus
  3. Bladder
     • Factors contributing to incontinence and poor emptying:
       • Poor sensation
       • Hypercontractility
       • Low compliance
       • Eventual myogenic failure
     • The renal dysfunction, vesicoureteral reflux, and voiding dysfunction seen in children with PUV are mediated by a dysfunctional bladder
     • Bladder problems are lifelong and change with age and management
  4. Ureters
     • Poor contractility and inability to coapt and transport urine
       • Many will improve initially, but most have chronic hydronephrosis

• Vesicoureteral Reflux (VUR) and Dysplasia Syndrome
  • In children with PUV, high-grade VUR is usually seen unilaterally into a poorly functioning renal unit, whereas the contralateral renal unit appears to have preserved renal function.
    • The VUR may serve as a pop-off mechanism in which the dysplastic kidney with reflux serves as a pressure reservoir mitigating damage to the contralateral kidney; this concept has been described as the VUR and dysplasia syndrome.
  • No protective benefit on long-term renal prognosis
    • Renal dysplasia is often detectable in the solitary functioning kidney increasing the likelihood of significant long-term renal impairment.

Diagnosis and Evaluation

• Often presents prenatally with hydronephrosis on ultrasound
  • Differential diagnosis of pre-natal hydronephrosis (4):
    1. Bladder outlet obstruction (PUV, urethral atresia)
    2. Prune-belly syndrome
    3. High-grade VUR
    4. Bilateral primary obstructing megaureters
  • Prenatal findings of a thickened, enlarged bladder and bilateral hydroureter with hydronephrosis (with or without oligohydramnios) in a male infant requires an early post-natal US and VCUG prior to the infant’s discharge from the postpartum unit
    • Pathognomonic findings on postnatal imaging confirm the diagnosis
• Post-natal Evaluation
  • Labs
    • Laboratory evaluation of a newborn will reflect maternal values and must be interpreted with caution.
      • After 48 hours, the maternal blood mediated through the placenta should clear, and the infant’s baseline laboratory values may be monitored
    • Serum creatinine plateau, even in unaffected children, may not be seen until days 65 to 220 of life
  • Imaging
    • Ultrasound
      • Pathognomonic US findings in PUV:
        1. Thickened, dilated bladder
        2. Multiple bladder diverticula
        3. Bilateral hydroureter and hydronephrosis
        4. Oligohydramnios
        5. Dilated posterior urethra displaying the “keyhole sign”
      • Other potential US findings
        • Increased renal echogenicity
          • Reliable indicator of renal damage
        • Urinomas
          • Forniceal rupture will appear on renal US as distorted renal parenchyma resulting from fluid trapped within the renal capsule, whereas transperitoneal transudation of fluid or bladder rupture will present as neonatal ascites
          • Bladder perforation is not a characteristic of posterior urethral valves, because the process actually leads to significant bladder wall hypertrophy.
    • Voiding cystourethrography (VCUG)
      • Definitive radiologic study in confirming the diagnosis of PUV
      • Should be performed as soon as an infant with suspected pre-natal findings of PUV is hemodynamically stabilized and able to undergo the study
      • Pathognomonic VCUG findings in PUV
        1. Thickened, trabeculated bladder
        2. Multiple bladder diverticuli
        3. High-grade vesicoureteral reflux
           • VCUG will reveal VUR in 50-80% of infants undergoing a workup for PUV
        4. Hypertrophied, elevated bladder neck
        5. Dilated and elongated posterior urethra with abrupt funneling
        6. Flattening of the verumontanum with dilation of the ejaculatory ducts
    • Nuclear Renal Scan
      • Delayed emptying of the tracer from the often dilated collecting systems should not be necessarily interpreted as ureterovesical junction obstruction requiring intervention
      • Placement of a urinary catheter is essential in a patient with VUR to minimize error in the calculation of renal function
• Delayed presentation
  • History and Physical Exam
    • A high degree of suspicion for PUV is still warranted in boys presenting with LUTS, especially those with:
      • Recurrent UTIs
      • Overflow incontinence
      • Gross hematuria
      • Renal dysfunction
      • Ejaculatory dysfunction (less commonly)

Management

• First-line: valve ablation
  • Cystoscopy with valve ablation is considered the preferred initial surgical option in a neonate diagnosed with PUV
  • A urethral catheter is typically placed for at least 24 hours after the procedure
    • Catheter placement into the bladder may be impeded by the hypertrophied and often elevated bladder neck; a coudé-tipped catheter will facilitate bladder drainage.
  • A VCUG must be repeated after valve ablation within 1 month to ensure that the valves are no longer visible
• Second-line: vesicostomy
  • Reserved for select cases in which valve ablation is not possible/successful
    • Does not inhibit bladder cycling because the bladder continues to contract
      • Best seen as a temporary diversion in children with PUV because it does not alter clinical outcomes as compared to primary ablation
  • Indications (2):
    1. Very low-birth-weight infant whose urethra cannot accommodate an endoscope
    2. Continued impaired renal function, high bladder urine volumes, and upper tract deterioration after valve ablation or urethral catheterization
  • The key operative step in creation of the vesicostomy is to ensure that the posterior wall of the bladder is taut
  • Complications
    • Most common: bladder prolapse and stenosis
    • Bladder prolapse
      • Exteriorization of the dome of the bladder by the Blocksom technique will prevent prolapse of the bladder
    • Stenosis of the vesicostomy
      • Late development of increasing hydronephrosis and a full bladder after vesicostomy would suggest the bladder is not draining well due to stenosis of the vesicostomy.
  • Management after vesicostomy
    • Approximately 75% of children will have normal bladder function after vesicostomy closure.
      • Preoperative videourodynamics showing a small bladder capacity do not predict eventual functional bladder capacity.
    • The eventual need for augmentation should be assessed with sequential follow-up after the vesicostomy has been closed.
      • The need for bladder augmentation is more related to the effects of the primary pathological condition on the detrusor.
        • Augmentation cystoplasty may be needed after undiversion in patients with PUV, based on the effect of the primary obstruction on long-term detrusor function.
      • There was at one time concern that a cutaneous vesicostomy caused permanent loss of bladder volume and compliance. However, recent studies show that it does not significantly affect either, and that in fact, the bladder cycles via a properly created vesicostomy.
• Third-line: upper urinary tract diversion
  • Examples include distal ureterostomy, proximal loop ureterostomy, cutaneous pyelostomy, ring ureterostomy, Sober Y ureterostomy
  • Requires a complex secondary procedure to reverse the diversion that can risk injury to the developing ureters.
  • Studies found no renal protective benefit
  • May be considered in an infant with complete decompression of the lower urinary tract but worsening renal function, increasing upper tract dilation, and possibly a clinical picture of sepsis
  • Whether upper urinary tract diversion or vesicostomy preserves renal function better than valve ablation alone cannot be definitively concluded because of the lack of controlled comparative studies or other available studies.  
• Circumcision
  • Should be strongly considered as a prophylactic measure for any boy diagnosed with PUV
  • Should be completed before giving any consideration to a ureteral reimplant in a scenario of frequent febrile UTI despite conservative measures.
• Nephroureterectomy
  • Rarely considered
  • If frequent UTI localizing to the nonfunctioning renal unit necessitates a nephrectomy, preserving the ureter for potential subsequent reconstruction, such as a ureteral augmentation, is recommended
• Management of VUR
  • Ablation of the valves or vesicostomy alone will resolve VUR in 25-40% of patients with VUR prior to ablation
  • All efforts in a symptomatic PUV patient with VUR must focus on addressing any persistent bladder outlet obstruction, reducing intravesical pressures by considering anticholinergic treatment, and treating underlying bladder dysfunction that is common in bladders exposed to fetal bladder outlet obstruction.
    • The focus of management for VUR in a child with PUV should be centered on the bladder, and ureteral reimplantation is rarely offered; understanding that reflux in these infants is a consequence of obstruction and the secondarily elevated bladder pressures is critical to management, and should render the ureteral reimplantation an option in atypical cases in which UTIs continue despite maximal bladder therapy
• Pre-natal management
  • A pre-natal vesicoamniotic shunt is considered in some centers in a fetus with a normal karyotype when antenatal US demonstrates (4):
    1. Oligohydramnios and
    2. Dilated bladder and
    3. Severe hydroureteronephrosis and
    4. Absence of renal cortical cystic lesions
  • Benefit
    • May reduce the severity of pulmonary hypoplasia
  • Not been shown to lower the incidence of end-stage renal disease

Follow-up

• Bladder Dysfunction
  • Must always be suspected in children with a history of valve ablation, even when not detected on clinical history alone
  • The bladder evolves through 3 patterns in boys with PUV:
    1. Infants: decreased capacity/compliance
    2. Childhood: detrusor overactivity and improved compliance bladder
    3. Adolescence: increased bladder capacity with myogenic failure (hypocontractility and atony)
  • Although an endoscopic ablation or urinary diversion will address the immediate uropathy, the embryologic insults to the bladder and kidneys manifest to varying extents, requiring that these boys remain under the extended care of urologists and nephrologists
  • In children with a history of PUV, follow-up should include upper tract assessment, uroflow and PVR (in toilet-trained children)
• Valve Bladder Syndrome
  • Processes contributing to the devolution of a bladder into a valve bladder in children with PUV (3):
    1. Polyuria
    2. Poor bladder compliance with high-pressure voiding and elevated wall tension bladder
    3. Residual urine volume
    • Although the bladder initially compensates for outlet obstruction by generating high voiding pressures, it begins to experience higher volumes of urine as a result of increasing urine production as the child grows. The polyuria caused by nephrogenic diabetes insipidus secondary to evolving renal impairment augments the urine volumes entering a bladder that is increasingly unable to empty completely. As the postvoid residuals increase, the bladder no longer has periods of complete relaxation, and the detrusor fibers are continuously in a state of partial or complete stretch, beginning a cascade of gene expression and phenotypic changes that further impair contractility of the bladder
  • Overnight bladder drainage is an important adjunct in therapy, and increasingly adopted as a standard intervention in children with classic evidence of developing a valve bladder syndrome.
  • Indications for nocturnal bladder drainage (4):
    1. Ureteral dilation and hydronephrosis do not respond to behavior modification
    2. Worsening hydronephrosis or renal function
    3. Increasing postvoid residuals
    4. Recurrent UTIs
  • When CIC or overnight bladder drainage is difficult because of an elevated bladder neck or sensate urethra, an appendicovesicostomy utilizing the Mitrofanoff principle can be used.
  • Augmentation cystoplasty is rarely utilized for a valve bladder in the contemporary era, perhaps because of improved understanding of bladder dysfunction, behavior modification, and timely institution of overnight bladder drainage. However, when faced with a small-capacity, high-pressure, thick-walled valve bladder with worsening upper tract anatomy refractory to conservative measures, augmentation may be considered.
• Prognostic indicators for renal function
  • Lifetime prevalence of end-stage renal disease in boys with PUV is between 20-50%
  • Risk factors known to affect the prognosis of an infant diagnosed with PUV include:
    1. Age at diagnosis
    2. Renal dysplasia with or without VUR
    3. Nadir creatinine value measured at 1 year of life
       • More accurate as a predictive tool than the value obtained at 1 month of age
    4. Recurrent UTIs
    5. Bladder dysfunction

Transplantation in PUV patients

• Patients with PUV are likely to have several comorbidities, including high-grade VUR into native nonfunctioning kidneys and valve bladder syndrome with a thick-walled, poorly contractile or hypercontractile bladder.
• A pediatric urologist must be a critical component of the transplantation team and should carefully examine the prospective recipient as part of the pre-transplantation evaluation.
• Transplant recipients in whom bladder dysfunction is incompletely managed or the bladder reservoir is not optimized have significantly higher complication rates and graft loss rates
• Transplantation into a valve-affected bladder may carry a higher risk of ureteral obstruction at site of ureteroneocystotomy, but there is no increased risk of graft loss compared to controls
• Video-urodynamics should be obtained for transplant candidates to determine the safe storage pressures and contractile function of the future reservoir.

Other urethral anomalies

Anterior Urethral Valves

• Most common congenital obstructive lesion of the anterior urethra, but 25-30x less common than PUV
• Often found in association with a large anterior urethral diverticulum; the valve itself is varyingly described as an obstruction resulting from a wall of the diverticulum obstructing flow or a semilunar fold draping down from the wall of the anterior urethra and interrupting urinary flow
• Renal function is better preserved in anterior urethral valves than that in posterior urethral valves
• Diagnosis and Evaluation
  • Presents at different ages based on the severity of the obstructive process.
    • Recall, PUV usually present pre-natally
  • History and Physical exam
    • Symptoms may consist of:
      • Postvoid dribbling and mild incontinence
      • Significant bulging of the distal penis
      • Palpable bladder with obstruction or even renal insufficiency
      • UTIs
  • Imaging
    • VCUG
      • Required to confirm the diagnosis
      • May demonstrate a dilated anterior urethra with proximal signs of chronic obstruction, including bladder diverticula and massive VUR.

Urethral Atresia

• Urethral atresia or congenital urethral stricture is a rarely described entity, likely because of its high associated mortality

Urethral Diverticulum

• A diverticulum of the bulbous urethra in a young male is most commonly related to dilation of a Cowper's gland duct.

Urethrorrhagia

• Definition of urethrorrhagia: spotting of blood on the underwear after urination, or voiding of clear urine followed by a few drops of blood
• Usually referred to as idiopathic urethrorrhagia
• Most commonly occurs in boys
• Etiology is unclear; hypotheses include meatal stenosis and dysfunctional elimination syndrome
• Typically considered benign and self-limited, though the visible blood tends to raise alarm within families
• Diagnosis and Evaluation
  • Routine cystoscopy is not necessary given the high rate of spontaneous resolution
  • Evaluation should focus on:
    • Detailed history of bowel and bladder function
    • Renal and bladder US
    • Urinary flow rate
    • PVR
  • Cystoscopy should be performed if urethrorrhagia becomes atypical (accompanied by symptoms of urethral stricture or increased urethral bleeding)

Questions

1. List imaging findings associated with PUV
2. List urologic and non-urologic complications of PUV

Answers

1. List imaging findings associated with PUV
2. List urologic and non-urologic complications of PUV

References

• Wein AJ, Kavoussi LR, Partin AW, Peters CA (eds): CAMPBELL-WALSH UROLOGY, ed 11. Philadelphia, Elsevier, 2015, vol 4, chap 141