INTRODUCTION — Posterior urethral valves (PUV) are obstructing membranous folds within the lumen of the posterior urethra that are the most common etiology of urinary tract obstruction in the newborn male.
The diagnosis and presentation of patients with posterior urethral valves will be reviewed here. The management of these patients is discussed separately. (See "Management of posterior urethral valves".)
EPIDEMIOLOGY — Posterior urethral valves (PUV) is the most common cause of urinary tract obstruction, occurring in 1 in 4000 to 8000 pregnancies (figure 1) [1-3]. PUV is also the most common cause of chronic renal disease due to urinary tract obstruction in children .
PATHOGENESIS — The pathogenesis of posterior urethral valves (PUV) appears to be due to an obstructing persistent urogenital membrane (figure 1). Although the exact mechanism resulting in this obstruction is not completely understood , it appears that the normal embryologic development of the male urethra between weeks 9 and 14 of gestation is disrupted, resulting in the obstructing membranous folds within the lumen of the posterior urethra.
Normal male urethral embryology — Between weeks four and six of gestation, the cloaca is divided into the anorectal canal and the urogenital sinus. Over the following weeks of gestation, the urogenital sinus is divided by the entrance of the mesonephric duct into the cephalad vesicourethral canal, giving rise to the bladder and pelvic urethra. The caudal portion of the urogenital sinus (genital tubercle) forms the phallic urethra. As the genital tubercle elongates in the male fetus, the urethral groove and folds are created. As the penile urethra grows, it moves towards the urethral plate of the glans penis. Complete fusion of the entire urethra occurs at approximately 14 weeks gestation.
PUV embryology — Several disruptions of the male embryologic urethral development have been proposed as the mechanism resulting in PUV .
●Persistence of the urogenital membrane with abnormal canalization of the urethra.
●Overgrowth of urethrovaginal folds.
●Abnormal integration of the Wolffian duct into the posterior urethra. Normally, the insertion of the Wolffian duct occurs in the cloaca before its division into the urogenital sinuses and anorectal canal. The Wolffian duct then involutes into thin mucosal folds (plicae colliculi) that run distal and lateral to the verumontanum in the midprostatic urethra. In this proposed mechanism, PUV are thought to arise from abnormal anterior insertion of the Wolffian duct into the cloaca that results in a thicker, more prominent, fused, and obstructing fold.
CLASSIFICATION — The traditional classification for posterior urethral valves (PUV) was developed by Young in 1919 based upon autopsies of a case series of PUV and is used clinically .
●Type 1 valve − The most common form is composed of a ridge from the verumontanum that divides into two leaflets, which attaches to the anterior urethra (figure 1).
●Type 2 valve − This type of valve is no longer considered a form of PUV but is believed to be a dissection artifact. It was reported to extend from the verumontanum towards the internal sphincter and bladder neck.
●Type 3 valve − This form is a diaphragm distal to the verumontanum with a central perforation, which may be a result of an attempt to place an urethral catheter.
In the 1990s, this classification was challenged based upon anatomic evaluation of cases using radiologic studies and direct observation by cystoscopy [7-9]. This reassessment suggested that PUV are the result of a single pathologic condition of an oblique membrane associated with the verumontanum, which was defined as congenital obstructive posterior urethral membrane (COPUM). In this reevaluation, COPUM was differentiated from Cobb's collar, which is defined as a congenital urethral stricture caused by a transverse membrane in the posterior urethra, and which has no relationship with the verumontanum . However, this new classification system has not been widely adopted into clinical practice.
Presentation — In the developed world, approximately one-third to one-half of posterior urethral valve (PUV) cases are identified by prenatal ultrasonography [2,3]. Patients who are diagnosed postnatally usually present either as a newborn or young infant with urinary tract symptoms, abdominal distension, or associated clinical manifestations, such as respiratory distress due to lung hypoplasia.
Prenatal — Prenatal ultrasonographic findings of bilateral hydronephrosis, dilated bladder, and a dilated posterior urethra (keyhole sign) in a male fetus is suggestive of PUV (image 1) . In addition, the bladder wall, which normally does not exceed 3 mm, may be thickened. Sonographic visualization of the PUV is not possible because of their small size.
In severe cases of obstruction, oligohydramnios (low volume of amniotic fluid) may also be present. Increased pressure in the urinary tract proximal to the obstruction may lead to rupture of the fornix or calyx in the kidney with development of urinary ascites or a perinephric urinoma. A large bladder diverticula or patent urachus may also develop. Other prenatal renal ultrasound findings may include increased renal echogenicity and cortical cysts suggestive of renal dysplasia, which is often associated with PUV.
The risk of perinatal mortality and postnatal chronic kidney disease are increased if prenatal ultrasound findings suggestive of PUV are noted before 24 weeks gestation, or if there is severe bilateral hydronephrosis with oligohydramnios or findings consistent with renal dysplasia [12-14]. When oligohydramnios is present in the second trimester, perinatal mortality can be as high as 90 to 95 percent [12,15]. (See "Fetal hydronephrosis: Etiology and prenatal management", section on 'Congenital anomalies of the kidney and urinary tract (CAKUT)' and 'Renal and urologic consequences' below and "Management of posterior urethral valves", section on 'Outcome'.)
Prenatal ultrasonography may not be highly reliable in differentiating fetuses with urinary obstruction from those without obstruction . In one retrospective report of 18 fetuses, two-thirds of the antenatal diagnoses corresponded to the postnatal diagnoses. Six cases of PUV were diagnosed prenatally; however, only two had PUV confirmed postnatally. As a result, fetal intervention based upon ultrasonographic findings must be considered cautiously. (See "Management of posterior urethral valves", section on 'Prenatal intervention'.)
Postnatal — Patients who are not detected prenatally usually are diagnosed as neonates or young infants. Approximately one-half will present with urinary tract infections .
●Neonates − Some neonates will present with respiratory distress due to lung hypoplasia. Lung hypoplasia develops because of oligohydramnios, as normal amniotic fluid levels are required for the canalicular phase of lung development, which occurs between 16 and 28 weeks gestation. One cause of oligohydramnios is decreased fetal urinary excretion in fetuses with severe bladder outlet obstruction. The outcome for neonates with lung hypoplasia due to severe PUV is poor. (See "Oligohydramnios: Etiology, diagnosis, and management in singleton gestations".)
Other neonates may present with abdominal distension due to enlarged overdistended bladder or urinary ascites, difficulty with voiding, or a poor urinary stream .
●Infants − Male infants with PUV may present with failure to thrive, urosepsis, poor urinary stream, and straining or grunting while voiding .
●Older boys − Older boys may present with urinary tract infections, day time and nocturnal incontinence (enuresis), and other symptoms of voiding dysfunction including frequency, straining to void, a poor urinary stream, and a large urinary volume at each void [18-21]. (See "Etiology and clinical features of bladder dysfunction in children", section on 'Definitions of symptoms'.)
Renal and urologic consequences — In patients with PUV, the following renal and urologic consequences of PUV are common.
●Chronic kidney disease
●Vesicoureteral reflux (VUR)
Chronic kidney disease — Chronic kidney disease (CKD) is commonly associated with PUV because many patients have renal dysplasia and/or acquired renal injury due to infection or ongoing issues with poor bladder function. Approximately 15 to 20 percent of patients with PUV progress to end-stage renal disease (ESRD) [22,23]. In some severe cases, end-stage renal disease (ESRD) occurs early in infancy, and these infants may require renal replacement therapy, in addition to medical management of the complications of renal failure. (See "Management of posterior urethral valves", section on 'Outcome' and "Chronic kidney disease in children: Overview of management".)
Associated renal dysplasia is often seen in patients with PUV. Prenatal renal parenchymal changes consistent with renal dysplasia are seen in approximately 60 percent of infants with prenatally diagnosed PUV . In addition, after bladder decompression, many neonates will have an elevated serum creatinine indicating impaired renal function due to renal dysplasia . Higher voiding pressures, which infants may have after valve ablation, are not necessarily associated with impaired renal function .
The relationship between the development of renal dysplasia and PUV is unknown. Proposed mechanisms include:
●Common developmental insult resulting in renal dysplasia and PUV.
●Causal relationship between back pressure from bladder outlet obstruction of PUV and defective nephron development. Support for this theory is based upon the observation of several conditions that result in a "pop off" mechanism with lowering of the intravesical pressure, which results in protection of the developing kidney and preservation of renal function. These conditions include large bladder diverticula, urinary ascites due to forniceal or calyceal extravasation (image 2), perirenal urinoma , and massive unilateral reflux with no renal function on the affected side but normal development of the contralateral side (Vesicoureteral reflux Unilateral Renal Dysplasia [VURD]) .
Recurrent infection resulting in renal scarring has been thought to be an important risk factor for CKD. However, in one study of 119 boys, recurrent urinary infection occurred in approximately one-half of the group and was not associated with an increased risk of developing ESRD .
Vesicoureteral reflux — VUR is present in approximately one-third to one-half of patients with PUV [19,23]. VUR is classified as secondary and is due to the increased intravesical pressure from bladder outlet obstruction, which results in failure of the normal closure of the ureterovesical junction during voiding (image 2 and image 3). VUR will resolve in at least one-third of patients with relief of the obstruction. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Secondary VUR'.)
VUR, particularly bilateral involvement, appears to be a risk factor for poor renal function and ESRD in patients with PUV [23,27]. In a case series of 200 patients with PUV, VUR was detected in 127 of 197 evaluable patients (64 percent), including 73 with bilateral VUR (37 percent) . Serum creatinine levels were higher in patients with VUR compared with those without VUR at diagnosis of PUV, and 6 and 12 months after PUV ablation. The incidence of ESRD before 16 years was highest in patients with bilateral VUR (25 percent), followed by unilateral VUR (7 percent) and no VUR (4 percent).
Bladder dysfunction — Bladder outlet obstruction results in muscular hypertrophy of the bladder wall and collagen deposition. These result in the ultrasonographic and radiologic appearance of a thickened bladder wall or trabeculations and diverticula (picture 1). A patent urachus may also be seen.
These bladder changes may lead to uninhibited bladder contractions (overactive bladder) and noncompliance that may persist after relief of the obstruction. Urodynamic findings typically demonstrate low capacity, poorly compliant bladders with high filling pressure . Imaging abnormalities include thickened bladder wall with trabeculations and diverticula. Other patients may exhibit myogenic failure due to overdistension. (See "Etiology and clinical features of bladder dysfunction in children" and "Management of bladder dysfunction in children".)
In two case series, one-third of patients had persistent bladder dysfunction after surgical PUV ablation, which required either pharmacologic therapy and/or clean intermittent catheterization (CIC) [18,22,23]. In one series, severe bladder dysfunction requiring CIC was predictive of ESRD .
Other urologic findings — In patients with PUV, other reported associated urological findings include cryptorchidism and inguinal hernias. In a case series of 200 patients with PUV, cryptorchidism and inguinal hernias were reported in 16 and 11 percent of patients, respectively .
Associated anomalies — Extra-urinary tract anomalies associated with PUV include tracheal hypoplasia, patent ductus arteriosus, total anomalous vein drainage, mitral stenosis, scoliosis, lower extremity deformations, and imperforate anus [22,23].
Laboratory studies — It is common for patients to have elevated serum creatinine levels and electrolyte disturbances (eg, hyperkalemia) that need to be addressed in the neonatal period. (See "Management of hyperkalemia in children" and "Fluid and electrolyte therapy in newborns" and "Neonatal acute kidney injury: Evaluation, management, and prognosis".)
DIAGNOSIS — A presumptive diagnosis is made by voiding cystourethrogram (VCUG) that demonstrates the hallmark findings of a dilated and elongated posterior urethra during the voiding phase (image 3 and image 4). The diagnosis must be made in the absence of a urethral catheter as the presence of a urethral catheter may falsely give the impression of a dilated urethra. Based upon the VCUG findings, cystoscopy is performed to confirm the diagnosis and ablate the PUV (picture 2). (See "Management of posterior urethral valves", section on 'Cystoscopy'.)
Ultrasonongraphy — Renal and bladder ultrasonography is performed to measure the degree of hydroureteronephrosis, if present, and assess renal parenchymal cortical thickness and renal corticomedullary differentiation. The bladder wall can appear thickened and is best assessed when it is full. In addition, if there is difficulty in inserting a urethral catheter, ultrasound is an excellent modality to document the correct placement of the catheter. (See "Management of posterior urethral valves", section on 'Postnatal management'.)
Radionuclide scans — Radionuclide scans are used to detect renal parenchymal abnormalities and assess the degree of obstruction.
●Static radionuclide scan using the radiotracer 99mTc–dimercaptosuccinic acid (DMSA) is the most useful modality for detection of focal renal parenchymal abnormalities and the differential assessment of renal function between the two kidneys. Following intravenous injection, DMSA is taken up by proximal tubular cells with only a minimal amount excreted in the urine, so the tracer accumulates over several hours within the tubule, providing a static image of functioning nephrons.
●Dynamic radionuclide scans assess renal excretory function and utilize either technetium 99mTc-diethylenetriamine pentaacetic acid (DTPA) or 99mTc-mercaptotriglycylglycine (MAG-3) as radiotracers.
The radiotracer is injected intravenously, taken up by the nephrons, and excreted primarily by glomerular filtration and proximal tubule secretion into the tubular lumen and subsequently into the bladder. As a result, the usefulness of this study is dependent upon a somewhat normal serum creatinine. MAG-3 is the preferred agent used for investigation of urinary tract obstruction in neonates who have immature glomerular filtration because of better visualization of the kidneys. (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Dynamic renal scan'.)
The MAG-3 radionuclide scan in conjunction with lasix (ie, diuretic renography) is used to diagnose urinary tract obstruction in infants with hydronephrosis. It measures the drainage time of the radiotracer from the renal pelvis and assesses total and each individual kidney's renal and excretory function. The details of this study are discussed in greater detail separately. (See "Fetal hydronephrosis: Postnatal management", section on 'Diuretic renography'.)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of posterior urethral valves (PUV) includes other causes of postbladder obstructive uropathy, which are rare.
●Agenesis or stricture/stenosis of the urethra
These causes are distinguished from PUV by voiding cystourethrogram (VCUG) and cystoscopy.
SUMMARY AND RECOMMENDATIONS
●Posterior urethral valves (PUV) are obstructing membranous folds within the lumen of the posterior urethra that are caused by a still yet to be determined disruption in the normal embryologic development of the male urethra (figure 1). (See 'Pathogenesis' above.)
●In the developed world, the majority of PUV cases are identified by prenatal ultrasonography. Prenatal ultrasonographic findings of bilateral hydronephrosis and a dilated bladder with a dilated posterior urethra (ie, keyhole sign) (image 1) in a male fetus is suggestive of PUV. (See 'Prenatal' above.)
●Patients who are diagnosed postnatally usually present either as a newborn with urinary tract symptoms, abdominal distension, or respiratory distress due to lung hypoplasia, or as a young infant with failure to thrive, urosepsis, poor urinary stream, or straining while voiding. Older boys may present with urinary tract infections, day time and nocturnal incontinence (enuresis), and symptoms of voiding dysfunction. (See 'Postnatal' above.)
●Clinical consequences of PUV include an increased risk of chronic kidney disease and bladder dysfunction. (See 'Renal and urologic consequences' above.)
●The presumptive diagnosis of PUV is made by voiding cystourethrogram (VCUG) that demonstrates the hallmark findings of a dilated and elongated posterior urethra with a thin linear defect during the voiding phase (image 3 and image 4). Confirmation of the diagnosis is made by cystoscopy. (See 'Diagnosis' above.)
3 : Current epidemiology and antenatal presentation of posterior urethral valves: Outcome of BAPS CASS National Audit.
8 : Congenital urethral obstruction: Cobb's collar or prolapsed congenital obstructive posterior urethral membrane (COPUM).
9 : Correlation of the endoscopic and radiological anatomy of congenital obstruction of the posterior urethra and the external sphincter.
11 : Posterior urethral valves and vesicoureteral reflux: can prenatal ultrasonography distinguish between these two conditions in male fetuses?
13 : Prenatally detected posterior urethral valves: qualitative assessment of second trimester scans and prediction of outcome.
14 : Prenatally detected posterior urethral valves: is gestational age at detection a predictor of outcome?
18 : Long-term bladder dysfunction and renal function in boys with posterior urethral valves based on urodynamic findings.
21 : Risk factors associated with chronic kidney disease in patients with posterior urethral valves without prenatal hydronephrosis.
22 : Long-term outcome of prenatally detected posterior urethral valves: single center study of 65 cases managed by primary valve ablation.
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