Management of posterior urethral valves

INTRODUCTION — 

Posterior urethral valves (PUV) are obstructing membranous folds within the lumen of the posterior urethra (figure 1). PUV are the most common etiology of urinary tract obstruction in the newborn male, occurring in 1 in 5000 to 8000 pregnancies [1]. PUV are also the most common cause of chronic kidney disease (CKD) due to urinary tract obstruction in children [2].

The management of PUV will be reviewed here. The clinical presentation and diagnosis of PUV are discussed separately. (See "Clinical presentation and diagnosis of posterior urethral valves".)

PRENATAL INTERVENTION — 

With prenatal detection of PUV and technologic advances in surgical equipment, the management of PUV has evolved to include prenatal surgical intervention. However, this remains investigational and the vast majority of affected infants should be treated soon after birth.

●Rationale – The first case of prenatal surgery to relieve obstructive uropathy was performed in 1981 [3,4]. Surgical intervention, primarily vesicoamniotic shunt placement, was based on the rationale that restoring amniotic fluid to normal levels by shunting fetal urine from the obstructed urinary system to the amniotic space would prevent lung hypoplasia and, thus, improve neonatal survival (figure 2). In addition, relief of the obstruction would also reduce back pressure and reduce injury to the developing nephron, thus improving long-term kidney function postnatally. (See "Clinical presentation and diagnosis of posterior urethral valves", section on 'Kidney and urologic complications' and "Fetal hydronephrosis: Etiology and prenatal management", section on 'Prenatal management'.)

●Candidates for prenatal intervention – Prenatal surgery for PUV should be considered only for fetuses who have a high risk of in utero or neonatal death diagnosed prior to 27 weeks gestation who have severe oligohydramnios, normal karyotype, and evidence of good kidney function based on fetal urine evaluation [5]. If prenatal intervention is being considered, it should only be performed in fetal treatment centers with considerable experience and expertise due to the risks to the mother and fetus.

Fetal urine evaluation is performed on at least two urine samples taken via a catheter that is placed into the fetal bladder under ultrasound guidance. The urine from the initial drainage is discarded, and a urine sample obtained after bladder refilling is sent for analysis. A favorable urine sample indicating good kidney function has a urine sodium of less than 100 mmol/L, chloride less than 90 mmol/L, osmolality less than 210 mOsm/L, and beta-2 microglobulin less than 6 mg/L [6,7].

●Outcomes – Data on outcomes of prenatal surgery for PUV suggest that it is associated with a significant risk of fetal morbidity, with limited benefit for long-term kidney outcomes, based on small case series in highly selected cohorts. This was illustrated in a case series from 1988 to 1991 of 40 fetuses cared for at one of the most active tertiary centers for fetal intervention [8]. Criteria for fetal intervention included normal karyotype, favorable fetal urinary electrolytes with beta-microglobulin levels predictive of normal kidney function, and a detailed prenatal kidney ultrasound that did not show evidence of cystic disease [8]. Of the 40 eligible fetuses, 36 underwent surgical intervention, including 14 with PUV at a mean gestational age of 22.5 weeks. In the 14 patients with PUV, procedures included placement of a vesicoamniotic shunt in nine cases, ablation of PUV in two cases, and fetal bladder marsupialization (ie, bladder was surgically opened and secured to the abdominal wall) in two cases, plus creation of a ureterostomy in one case. The following findings were noted in the 14 PUV cases:

•Five deaths occurred in infants who were born prematurely and had respiratory failure.

•One pregnancy was terminated because of evidence of shunt failure and findings indicative of poor lung and kidney development and function.

•Eight patients were alive at a mean follow-up of 11.6 years. Five patients had chronic kidney disease (CKD) demonstrated by an elevated serum creatinine, of whom two had undergone kidney transplantation, and another patient was awaiting organ donation.

Similar results were seen in a case series from a single fetal treatment center of 20 fetuses with lower urinary tract obstruction, including seven with PUV [9]. The mean gestational age was 34.6 weeks, with a mean birth weight of 2.57 kg. There were two neonatal deaths due to pulmonary hypoplasia. Among the survivors, six developed kidney failure requiring either dialysis or kidney transplantation and four had minor kidney function impairment at a mean age of 5.83 years.

In a multicenter retrospective report of 50 fetal cystoscopies performed from 2004 to 2013, laser fulguration of PUV was performed in 30 fetuses [10]. Four pregnancies were terminated, and 24 live-born infants were delivered at a mean gestational age of 35 weeks. Seven infants died in the neonatal period. All infants who survived the neonatal period were alive at one year of age, including 13 with normal kidney function, and, at two years of life, there were 15 survivors, including 11 with normal kidney function. Two patients were receiving dialysis within two years of life. These results demonstrated a significant mortality and morbidity rate of prenatal intervention for PUV.

Advances in fetal cystoscopy with the use of a flexible fetoscope have the potential to make fetal PUV ablation more successful. Improvements in the design of vesiocoamniotic shunts to reduce complications of blockage and shunt dislodgement are ongoing. Hopefully, these efforts to develop new technology and increased training and experience of the surgeon will result in improved mortality and morbidity outcomes [5].

INITIAL POSTNATAL MANAGEMENT — 

For newborns with suspected or confirmed PUV, initial postnatal management includes stabilization of the patient and drainage of the urinary tract.

Medical management — Any electrolyte abnormalities, particularly hyperkalemia, should be corrected and respiratory distress managed as needed. In addition, kidney function is monitored before, during temporary bladder drainage, and after PUV ablation. This is accomplished by obtaining a basic metabolic panel, looking for the trend in serum creatinine toward normalization or stabilization. (See "Fluid and electrolyte therapy in newborns".)

In addition, kidney/bladder ultrasound and voiding cystourethrogram should be done soon after birth to confirm the diagnosis, once the patient is medically stable. (See "Clinical presentation and diagnosis of posterior urethral valves".)

Temporary drainage of the urinary tract — Drainage of the bladder should be done once the patient is stabilized. In most instances, temporary drainage is performed by placement of a catheter in the bladder. In some centers, primary ablation is used without initial drainage [11].

To drain the bladder, we generally use a soft feeding tube rather than a Foley catheter with a balloon. The feeding tube has a larger internal diameter, allowing for better drainage, and the inflated balloon of the Foley catheter may occlude the ureteral orifices. We typically use an 8-French or greater feeding tube, depending on the size of the urethral meatus. Ultrasonography can be used to document the correct placement of the catheter into the bladder. It is common for any type of urethral catheter to coil in the dilated posterior urethra. If urethral catheter drainage cannot be established, emergency consultation with a pediatric urologist is necessary for cystoscopic evaluation.

Once drainage is established, the patient may have large urinary water and solute losses because of tubular dysfunction, resulting in an inability to concentrate the urine or normally absorb solutes (eg, sodium and potassium) [12]. In addition, some patients with PUV due to urinary obstruction may have type IV renal tubular acidosis. As a result, careful monitoring of serum electrolytes, including serum bicarbonate, and fluid status is required, with timely replacement of fluid and electrolytes as needed.

SURGICAL INTERVENTION — 

For most infants, a provisional diagnosis of PUV is made based on the voiding cystourethrogram, which demonstrates the PUV, dilated posterior urethra, hypertrophied bladder neck, trabeculated bladder, bladder diverticulum, and vesicoureteral reflux (VUR). The classic approach has been a contrast voiding cystourethrogram, but more recent reports describe accurate diagnosis in experienced centers using contrast-enhanced sonography. (See "Clinical presentation and diagnosis of posterior urethral valves", section on 'Diagnosis'.)

Cystoscopy (most infants) — For term infants who are stable, primary valve ablation via cystoscopy is the preferred initial surgical treatment. The goal is to relieve the obstruction, thereby preserving bladder and kidney function [4,11,13]. The timing of this procedure depends on the overall health status of the neonate and issues with general anesthesia. The ability to perform this procedure is determined by whether the size of the male urethra can accommodate the neonatal cystoscope.

Valve ablation relieves the urethral obstruction in most patients [11,14-16]. With relief of bladder pressure in those patients with vesicoureteral reflux, resolution of vesicoureteral reflux will occur in one-third of the patients after ablation.

Temporary catheter drainage (preterm or unstable infants) — For preterm infants, cystoscopy is challenging. For these infants, a small catheter (5- or 8-French feeding tube) is temporarily placed into the bladder through the urethra for urinary drainage. An observational study of 126 neonatal males reported that progressive urethral catheter dilation improved the rate of successful primary ablation to 97 percent, compared with the 82 percent that was cited in the literature [17]. However, we have found that placement of a temporary feeding tube is sufficient until the urethra is large enough to accommodate the cystoscope.

Although primary ablation is not generally performed in premature infants, in one small case series of 17 low birth weight infants (median birth weight 2100 g, range 1760 to 2690 g), a Fogarty catheter under direct visual guidance of a neonatal cystoscope was used to disrupt PUV [18]. In 14 of the surviving infants (three died of causes unrelated to the procedure), voiding cystourethrography demonstrated effective ablation and adequate bladder drainage. The advantage of this technique is that it avoids long-term catheterization and the need for vesicostomy. However, the use of this technique has been very limited and it should only be performed by an experienced pediatric urologist for the rare premature infant with obstructive uropathy due to PUV.

Other procedures — A diversion procedure is used when primary valve ablation is not feasible. In a meta-analysis (30 studies, 1547 infants), infants managed with primary diversion were more likely to develop kidney function impairment compared with those undergoing primary valve ablation (odds ratio 0.6, 95% CI 0.44-0.88) [19]. However, after adjusting for baseline kidney function, there were no significant differences in the risk for kidney function impairment or bladder dysfunction during childhood. The certainty of this conclusion is limited by heterogeneity in patient management and definitions of kidney function impairment.

Vesicostomy — If primary valve ablation cannot be done, generally for technical reasons, vesicostomy is the next preferred procedure. Vesicostomy provides bladder drainage by bladder cycling under low pressure. When the patient reaches an appropriate age, the vesicostomy can be closed along with PUV ablation and additional bladder management as necessary.

Higher diversions — Higher diversions with cutaneous ureterostomies and pyelostomies are rarely indicated and do not improve outcomes compared with vesicostomy. They commit a patient to subsequent major upper tract reconstruction. In addition, higher diversions disrupt the filling and emptying of the bladder, which may further impact bladder function [20].

POSTPROCEDURE MANAGEMENT — 

After a successful procedure that relieves or bypasses the intervention, management includes detecting and treating bladder dysfunction, monitoring kidney function, and, if necessary, managing the consequences of chronic kidney disease (CKD).

Bladder function

●Monitoring – Bladder function should be evaluated by imaging with kidney/bladder ultrasound and urodynamic studies. The timing of these studies depends on the patient's kidney function and their ability to void spontaneously. A voiding cystourethrogram should be performed after valve ablation to confirm surgical success. (See "Clinical presentation and diagnosis of posterior urethral valves", section on 'Bladder dysfunction'.)

●Pathogenesis and clinical manifestations – Even after successful PUV ablation, approximately one-third of patients have persistent bladder muscle hypertrophy, leading to overactive bladder (high bladder filling pressures with low bladder capacity), which predisposes to VUR. Imaging may show hydronephrosis and hydroureteronephrosis. Other patients may develop an underactive bladder (myogenic failure) due to chronic overdistension, which can be exacerbated by polyuria caused by kidney dysfunction. (See "Clinical presentation and diagnosis of posterior urethral valves", section on 'Kidney and urologic complications'.)

●Management – Patients with severe bladder dysfunction with high bladder pressures, incomplete bladder emptying, and persistent hydroureteronephrosis should be managed with clean intermittent catheterization (CIC) and night drainage (in selected cases). Other interventions may include anticholinergic medications, beta-3 adrenoreceptor agonists (eg, mirabegron), and intravesical injection of botulinum toxin to reduce bladder pressures and promote complete bladder emptying [21]. These interventions can reduce VUR and delay progression of bladder dysfunction and CKD [22,23]. (See "Clinical presentation and diagnosis of posterior urethral valves", section on 'Bladder dysfunction' and "Management of bladder dysfunction in children".)

In a series of 18 boys who had successful ablation of PUV, nighttime drainage markedly improved their hydroureteronephrosis [24]. In another series of 119 patients with PUV who were almost all treated with initial early bladder drainage and cystoscopy with primary ablation, one-third of patients had severe bladder dysfunction and required CIC [14]. In another study, although 27 of 65 patients had symptoms of bladder dysfunction, continence was achieved in 42 of 55 toilet-trained children and only three required CIC [11]. In both reports, pharmacologic treatment using anticholinergic and alpha-blocker medications was used in children, depending on the results of urodynamic testing. In a small case series of 18 patients with high voiding pressures and/or small bladder capacity, early administration of oxybutynin (an anticholinergic agent) after PUV ablation was associated with improved bladder function on urodynamic testing prior to toilet training [25].

Kidney function — Because there is a high risk of CKD in these patients, ongoing monitoring of the kidney function is important. In patients with CKD, management is directed at caring for the associated complications of CKD and is discussed separately. (See "Chronic kidney disease in children: Overview of management" and 'Outcome' below.)

Patients with CKD may have a urinary concentrating defect, resulting in excessive urinary losses. This may overwhelm the carrying capacity of the urinary tract, resulting in an enlarged and poorly functioning bladder and persistent hydronephrosis. In these patients, nighttime catheter drainage to completely decompress the urinary tract may be an effective intervention [23].

OUTCOME

Survival — The 10-year survival is over 90 percent for patients diagnosed within the first year of life. In a retrospective review from the Pediatric Health Information System (PHIS) database of 685 patients (5 percent) with PUV diagnosed and treated by one year of life between 1992 and 2006, 34 children (5 percent) died: over one-half during their first hospitalization, primarily due to pulmonary hypoplasia [26]. In this cohort, the probability of 10-year survival was 94 percent.

Kidney function — Despite prenatal diagnosis and early intervention, approximately 30 to 40 percent of patients with PUV will develop chronic kidney disease (CKD) and 10 to 15 percent develop kidney failure during childhood [27,28]. Although most of the progression occurs during the first five years of life, kidney function often continues to decline into adulthood, such that up to 25 percent develop kidney failure by early adulthood [26,27,29,30]. Predictors of long-term kidney outcomes include nadir serum creatinine, severity of renal dysplasia, bladder dysfunction, and bilateral vesicoureteral reflux (VUR) [27]. Nadir creatinine also predicts bladder dysfunction after age five years [31].

A preponderance of evidence suggests that prenatal diagnosis is associated with worse kidney outcomes, presumably because earlier diagnosis reflects more severe disease (despite the opportunity for earlier intervention) [27,30,32-34]. In a large case series from Canada, the long-term risk of developing CKD was higher in infants diagnosed before three months of age (63 percent) compared with those diagnosed between 3 and 12 months (22 percent) [27]. Similarly, in another large case series from Finland, the long-term risk of kidney failure was higher in patients with a prenatal diagnosis of PUV (55 percent) compared with those diagnosed because of early neonatal problems (32 percent) or because of infection (22 percent) [30]. Contrasting results come from a large case series of 315 patients from two centers treated between 1990 and 2010, patients who were prenatally diagnosed (median age of valve ablation one month, range one day to three months) compared with those diagnosed postnatally (median age of valve ablation three years, range 1 month to 15 years) were less likely to have developed chronic kidney disease (CKD) at the end of a median follow-up of 5.5 years (19 versus 40 percent) [33]. Mean serum creatinine values for the two groups were similar at diagnosis but were lower for the prenatally diagnosed group at the end of follow-up (0.96 versus 1.75 mg/dL).

The high rates of CKD and kidney failure underscore the importance of ongoing monitoring of kidney and bladder function. This permits early detection and treatment of associated CKD medical conditions, as well as counseling to patients at risk for kidney failure and their caregivers regarding options for kidney replacement therapy. (See "Chronic kidney disease in children: Overview of management".)

Lower urinary tract function — After PUV ablation, patients are at risk for bladder dysfunction and may require clean intermittent catheterization (CIC) [35,36] and have delays in achieving daytime and nighttime urinary continence.

A case series of 76 patients with PUV reported delays for achieving both daytime (mean age 5.5±3.3 versus 2.3±0.5 years) and nighttime urinary continence (mean age 5.4±3.0 versus 2.9±1.2 years) compared with reference population [37].

Lower urinary tract symptoms are commonly seen in adult patients with PUV [36,38]. In one study, adult patients (median age 38.5 years) with PUV were more likely than age- and sex-matched controls to have one or more moderate to severe lower urinary tract symptoms (32.4 versus 15.8 percent) [38]. Symptoms included mild hesitancy, weak stream, incomplete emptying, staining, and urgency and stress incontinence.

Kidney transplantation — As outlined above, approximately 25 to 50 percent of patients with PUV progress to kidney failure by adulthood and thus require dialysis or transplantation.

After kidney transplantation, bladder dysfunction can adversely affect allograft survival for patients with PUV. Continued bladder management based on urodynamic evaluation is indicated. As described above, this includes CIC, night drainage, medications to reduce bladder pressure, and botulinum toxin bladder treatments (see 'Postprocedure management' above). With aggressive bladder management, allograft survival is similar to that of other children undergoing kidney transplantation, based on case series comparing the outcomes of boys with PUV with children with other underlying primary causes of kidney failure [39,40]. Data are inconclusive regarding optimal bladder management after transplantation and whether this improves graft survival [41,42]. (See "Kidney transplantation in children: Outcomes".)

SUMMARY AND RECOMMENDATIONS

●Definition – Posterior urethral valves (PUV) are obstructing membranous folds within the lumen of the posterior urethra that are the most common cause of congenital urinary obstruction (figure 1).

●Indications for prenatal surgery – We suggest that fetal surgery and/or prenatal intervention only be considered in select patients with a high risk of perinatal mortality because of the morbidity associated with fetal intervention and the lack of evidence that intervention reduces the risk of chronic kidney disease (CKD) (Grade 2C). In addition, fetal surgery should be performed in centers with expertise in these procedures. (See 'Prenatal intervention' above.)

●Postnatal management – The postnatal management of PUV includes stabilization of the patient and drainage of the urinary tract. Medical management includes correction of electrolyte abnormalities and treatment for possible complications such as respiratory distress and infection. (See 'Initial postnatal management' above.)

●Valve ablation – With advancements in surgical technique and instruments, primary ablation during cystoscopy has become the preferred surgical procedure to relieve the obstruction. It can be performed in most neonates with PUV, including some premature infants. If primary valve ablation cannot be done, vesicostomy is the next preferred procedure. (See 'Cystoscopy (most infants)' above.)

●Possible urologic complications – Although all patients with PUV are at risk for developing CKD, patients with a persistently elevated creatinine after relief of their urinary obstruction (eg, PUV ablation) are at increased risk for kidney failure. In addition, a significant number of patients will have persistent bladder dysfunction, vesicoureteral reflux, and/or hydronephrosis, which, in some cases, may require clean intermittent catheterization (CIC), night drainage, anticholinergic and beta-3 adrenoreceptor agonist medications, and bladder botulinum toxin treatment. (See 'Postprocedure management' above and "Clinical presentation and diagnosis of posterior urethral valves", section on 'Kidney and urologic complications'.)