Official reprint from UpToDate www.uptodate.

com

Back | Print

Clinical presentation and diagnosis of posterior urethral valves

Author Nicholas Holmes, MD Section Editor Laurence Baskin, MD Deputy Editor Melanie S Kim, MD

Last literature review version 17.1: January 2009 | This topic last updated: September 30, 2008 (More) 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, occurring in 1 in 5000 to 8000 pregnancies [ 1] . PUV are also the most common cause of chronic renal disease due to urinary tract obstruction in children [ 2] . 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" ). PATHOGENESIS The pathogenesis of PUV appears to be due to an obstructing persistent urogenital membrane. Although the exact mechanism resulting in this obstruction is not completely understood [ 3] , it appears that the normal embryologic development of the male urethra between weeks 9 and 14 of gestation is disrupted. 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 tubercule) 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 about 14 weeks gestation. PUV embryology Several disruptions of the male embryologic urethral development have been proposed as the mechanism resulting in PUV [ 3] .

These are based upon published anatomical descriptions in the literature and include the following [ 3] : 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 PUV was developed by Young in 1919 based upon autopsies of a case series of PUV as follows [ 4] : 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. 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 [ 5-7] . 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 that is defined as a congenital urethral stricture caused by a transverse membrane in the posterior urethra, which has no relationship with the verumontanum [ 8] . This new classification system has not yet been widely adopted into clinical practice. CLINICAL MANIFESTATIONS Presentation In the developed world, the vast majority of PUV cases are

identified by prenatal ultrasonography. 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 (show ultrasound 1 ) and a dilated bladder with a dilated posterior urethra (keyhole sign, show ultrasound 2 ) in a male fetus is suggestive of PUV. 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 there is severe bilateral hydronephrosis with oligohydramnios or findings consistent with renal dysplasia [ 9-11] . When oligohydramnios is present in the second trimester, perinatal mortality can be as high as 90 to 95 percent [ 9,12] . (See "Overview of antenatal hydronephrosis" , section on Congenital anomalies of the kidney and urinary tract (CAKUT) and see "Renal and urologic manifestations" below and see "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 [ 13] . In one retrospective report of 18 fetuses, two-thirds of the antenatal diagnosis corresponded to the postnatal diagnosis. 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 that are not detected prenatally usually are diagnosed as neonates or young infants. 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" ). Other neonates may present with abdominal distension due to enlarged overdistended bladder or urinary ascites, difficulty with voiding, or a poor urinary stream [ 14] . Infants Male infants with PUV may present with failure to thrive, urosepsis, poor urinary stream, and straining or grunting while voiding [15] . 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 [ 15-17] . (See "Etiology and clinical features of voiding dysfunction in children" , section on Definitions of symptoms). Renal and urologic manifestations Renal and urologic manifestations are common in patients with PUV. They include: Chronic kidney disease Vesicoureteral reflux (VUR) Bladder dysfunction 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 on-going issues with poor bladder function. About 15 to 20 percent of patients progress to end-stage renal disease (ESRD) [ 18,19] . (See "Management of posterior urethral valves" , section on Outcome). Associated renal dysplasia is often seen in patients with PUV. Prenatal renal parenchymal changes consistent with renal dysplasia are seen in about 60 percent of infants with prenatally diagnosed PUV [ 18] . In addition, after bladder decompression, many neonates will have an elevated serum creatinine indicating impaired renal function due to renal dysplasia [ 19] . 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 calcyceal extravasation ( show radiograph 1 ), 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]) [ 20] . 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 about one-half of the group and was not associated with an increase risk of developing ESRD [ 19] . Vesicoureteral reflux VUR is present in about one-third to one-half of patients with PUV [ 16,19] . 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 uretervesical junction during voiding (show radiograph 1 and show radiograph 2 ). VUR will resolve in at least one-third of patients with relief of the obstruction. It is unclear whether or not VUR has an independent effect on long-term renal function [ 19] . (See "Presentation, diagnosis, and clinical course of vesicoureteral reflux" , section on Secondary VUR). Bladder dysfunction Bladder outlet obstruction results in muscular hypertrophy of the bladder wall and collagen deposition. These result in the ultrasonographic appearance of a thickened bladder wall or trabeculations and diverticula seen on voiding cystoureothrogram (VCUG). 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 [ 19] . 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 voiding dysfunction in children" and see "Management of voiding 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 catherization (CIC) [ 15,18,19 ] . In one series, severe bladder dysfunction requiring CIC was predictive of ESRD [ 19] . 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 [ 21] . 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 [ 18,19] . DIAGNOSIS The diagnosis is made by voiding cystourethrogram (VCUG) that demonstrates the hallmark findings of a dilated and elongated posterior urethra during the voiding phase ( show radiograph 2 and show radiograph 3 ) when the urethral catheter is no longer present. The presence of a urethral catheter may falsely give the impression of a dilated urethra. Characteristic bladder features supporting the diagnosis of PUV include a thickened, heavily trabeculated wall and diverticulum. A patent urachus may also be visualized. As discussed above, about one third to one-half of patients will have either unilateral or bilateral VUR, which is also detected by the VCUG [16,19] . Based upon the VCUG findings, cystoscopy is performed to confirm the diagnosis and ablate the PUV. ( See "Management of posterior urethral valves" , section on Cystoscopy). Renal and bladder ultrasonography is also 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). Other studies 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 is 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 "Postnatal management of antenatal hydronephrosis" , section on Diuretic renography). Laboratory studies Initial essential laboratory studies include serum electrolytes, blood urea nitrogen (BUN), and creatinine. It is not uncommon for patients to have elevated creatinines with electrolyte disturbances (eg, hyperkalemia) that need to be addressed in the neonatal period. In some severe cases, 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 "Overview of the management of chronic kidney disease in children" ). DIFFERENTIAL DIAGNOSIS The differential diagnosis of PUV includes other causes of obstructive uropathy such as: Agenesis or stricture/stenosis of the urethra Although more commonly observed in girls, the megalourethra, megacystis, microcolon syndrome These causes are distinguished from PUV by VCUG and cystoscopy. SUMMARY AND RECOMMENDATION 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. ( See "Pathogenesis" above ). In the developed world, the vast majority of PUV cases are identified by prenatal ultrasonography. Prenatal ultrasonographic findings of bilateral hydronephrosis ( show ultrasound 1 ) and a dilated bladder with a

dilated posterior urethra (keyhole sign, show ultrasound 2 ) 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 manifestations of the PUV include an increased risk of chronic kidney disease and bladder dysfunction. ( See "Renal and urologic manifestations" 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 ( show radiograph 2 and show radiograph 3 ). Confirmation of the diagnosis is made by cystoscopy. ( See "Diagnosis" above ).

Use of UpToDate is subject to the Subscription and License Agreement . REFERENCES

1. Brown, T, Mandell, J, Lebowitz, RL. Neonatal hydronephrosis in the era of sonography. AJR Am J Roentgenol 1987; 148:959. 2. Warshaw, BL, Edelbrock, HH, Ettenger, RB, et al. Renal transplantation in children with obstructive uropathy. J Urol 1980; 123:737. 3. Krishnan, A, de Souza, A, Konijeti, R, Baskin, LS. The anatomy and embryology of posterior urethral valves. J Urol 2006; 175:1214. 4. Young, HH, Frontz, WA, Baldwin, JC. Congenital obstruction of the posterior urethra. J Urol 1919; 3:289. 5. Dewan, PA, Zappala, SM, Ransley, PG, Duffy, PG. Endoscopic reappraisal of the morphology of congenital obstruction of the posterior urethra. Br J Urol 1992; 70:439. 6. Dewan, PA, Keenan, RJ, Morris, LL, Le Quesne, GW. Congenital urethral obstruction: Cobb's collar or prolapsed congenital obstructive posterior urethral membrane (COPUM). Br J Urol 1994; 73:91. 7. Dewan, PA, Pillay, S, Kaye, K. Correlation of the endoscopic and radiological anatomy of congenital obstruction of the posterior urethra and the external sphincter. Br J Urol 1997; 79:790. 8. Dewan, PA, Goh, DG. Variable expression of the congenital obstructive

9. 10.

11.

12. 13. 14. 15.

16.

17.

18.

19.

20. 21.

posterior urethral membrane. Urology 1995; 45:507. Mahony, BS, Callen, PW, Filly, RA. Fetal urethral obstruction: US evaluation. Radiology 1985; 157:221. Hutton, KA, Thomas, DF, Davies, BW. Prenatally detected posterior urethral valves: qualitative assessment of second trimester scans and prediction of outcome. J Urol 1997; 158:1022. Hutton, KA, Thomas, DF, Arthur, RJ, Smith, SE. Prenatally detected posterior urethral valves: is gestational age at detection a predictor of outcome?. J Urol 1994; 152:698. Freedman, AL, Johnson, MP, Gonzalez, R. Fetal therapy for obstructive uropathy: past, present.future?. Pediatr Nephrol 2000; 14:167. Sholder, AJ, Maizels, M, Depp, R, et al. Caution in antenatal intervention. J Urol 1988; 139:1026. Macpherson, RI, Leithiser, RE, Gordon, L, Turner, WR. Posterior urethral valves: an update and review. Radiographics 1986; 6:753. Ghanem, MA, Wolffenbuttel, KP, De Vylder, A, Nijman, RJ. Long-term bladder dysfunction and renal function in boys with posterior urethral valves based on urodynamic findings. J Urol 2004; 171:2409. Bomalaski, MD, Anema, JG, Coplen, DE, et al. Delayed presentation of posterior urethral valves: a not so benign condition. J Urol 1999; 162:2130. Ziylan, O, Oktar, T, Ander, H, et al. The impact of late presentation of posterior urethral valves on bladder and renal function. J Urol 2006; 175:1894. Sarhan, O, Zaccaria, I, Macher, MA, et al. Long-term outcome of prenatally detected posterior urethral valves: single center study of 65 cases managed by primary valve ablation. J Urol 2008; 179:307. DeFoor, W, Clark, C, Jackson, E, et al. Risk factors for end stage renal disease in children with posterior urethral valves. J Urol 2008; 180:1705. Hoover, DL, Duckett, JW Jr. Posterior urethral valves, unilateral reflux and renal dysplasia: a syndrome. J Urol 1982; 128:994. Heikkila, J, Taskinen, S, Toppari, J, Rintala, R. Posterior urethral valves are often associated with cryptorchidism and inguinal hernias. J Urol 2008; 180:715.

GRAPHICS

Bilateral grade II hydronephrosis

Calipers are on the left ureter, which measures 1 cm. Courtesy of Tulin Ozcan, MD.

Keyhole sign

Keyhole sign suggestive of posterior urethral valves (PUV). Bladder and proximal urethra are enlarged due to obstruction from PUV. Courtesy of Tulin Ozcan, MD.

PUV VUR urine extravasation

VCUG of patient with severe urethral obstruction secondary to posterior urethral valves. Has associated high grade reflux with urinary extravasation from kidney (white arrows). Courtesy of Nicholas Holmes, MD.

VCUG of patient with PUV

White arrows outline dilated urethra. Black arrows outline dilated ureter with associated reflux. Courtesy of Nicholas Holmes, MD.

VCUG PUV dilated post urethra

Voiding cystourethrogram of patient with posterior urethral valves noted by white arrows with dilated posterior urethra. Small capacity bladder with vesicoureteral reflux (black arrows). Courtesy of Nicholas Holmes, MD.

2009 UpToDate, Inc. All rights reserved. | Subscription and License Agreement Licensed to: brw brw