Primary megaureter in infants and children

INTRODUCTION — Megaureter is defined as a ureter that exceeds the upper limits of normal size. In children, any ureter greater than 7 mm in diameter is considered a megaureter based on measurements in fetuses greater than 30 weeks gestation and children <12 years [1].

Primary megaureter is a result of a functional or anatomical abnormality involving the ureterovesical junction (figure 1), whereas secondary megaureter results from abnormalities that involve the bladder or urethra (eg, myelomeningocele/neurogenic bladder, prune-belly syndrome, and posterior urethral valves [PUV]).

Primary megaureter in infants and children will be reviewed here. Related topics include:

●(See "Fetal hydronephrosis: Etiology and prenatal management" and "Postnatal evaluation and management of hydronephrosis".)

●(See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux" and "Management of vesicoureteral reflux".)

●(See "Urinary tract infections in children: Epidemiology and risk factors".)

●(See "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)".)

CLASSIFICATION — Primary megaureter is classified according to the presence or absence of reflux and obstruction, which are key characteristics for management decisions. (See 'Postnatal management' below.)

The types of megaureter are as follows:

●Nonrefluxing

•Nonobstructed – This common variant is also called primary dilated megaureter.

•Obstructed – This variant is associated with ectopic ureters, although not always, and typically presents with prenatal sonographic screening or postnatally with symptoms of pain or urinary tract infection. For example, children with duplex systems (a common anomaly in which the renal collection system is duplicated), the upper pole ureter that is nonrefluxing is ectopic and inserts past the bladder in the vagina or introitus in girls or prostatic urethra or bladder neck in males (figure 2). (See "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Duplication' and "Ectopic ureter".)

●Refluxing

•Nonobstructed – This common variant is associated with a high-grade (ie, grades IV through V) vesicoureteral reflux with a dilated ureter (figure 3). (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Grading'.)

•Obstructed – This rare variant is often associated with an ectopic ureter. (See "Ectopic ureter".)

EPIDEMIOLOGY — Primary megaureter is the second most common cause of hydronephrosis in the newborn (after ureteropelvic obstruction), accounting for approximately 20 percent of cases. The incidence of primary megaureter is estimated as 0.36 per 1000 live births [2].

Boys are affected more commonly than girls, and lesions are found more frequently on the left than on the right side [3,4]. Megaureter is bilateral in approximately 30 to 40 percent of cases (image 1) [3,5,6].

PATHOPHYSIOLOGY — The pathogenesis of primary megaureter is uncertain. It appears to be most commonly due to an abnormality or delay in the development of the muscle in the distal ureter adjacent to the ureterovesical junction at 20 weeks gestation [7]. This results in the formation of an aperistaltic segment (movie 1), which leads to functional obstruction. Much rarer causes of megaureter include congenital ureteral strictures or ureteral valves.

The refluxing megaureter also has an abnormal ureterovesical tunnel that allows urine to reflux up the ureter. The reflux primarily occurs during voiding when the bladder pressure is highest but also may occur during bladder filling. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Definition and pathogenesis'.)

CLINICAL PRESENTATION

Antenatal — Primary megaureter usually is detected on antenatal ultrasonography. The ultrasound demonstrates a dilated ureter (>7 mm in diameter), often with associated hydronephrosis [8]. Affected newborn infants are asymptomatic and typically have a normal physical examination, urinalysis, and serum creatinine.

Postnatal — When the condition is not detected antenatally, children can present at any age after the newborn period with urinary tract infection, hematuria, abdominal pain and/or mass, or uremia. For some patients, the finding may be detected incidentally during evaluation of other conditions. Symptomatic presentation is typically due to an obstructed ureter.

Both renal and nonrenal anomalies can be seen in patients with primary megaureter [4]. Renal and urologic findings include ipsilateral ureteropelvic junction obstruction (UPJO), contralateral vesicoureteral reflux, and renal hypoplasia/dysplasia. Reported but rare nonrenal findings include ear tags, undescended testes, dermal sinus, tracheomalacia, and aortic aneurysm [4].

PRENATAL MANAGEMENT — Primary megaureter due to ureterovesical junction obstruction has a good prognosis. These fetuses can be followed expectantly in the prenatal period, without intervention or early delivery. Expectant routine prenatal management is recommended as long as the amniotic fluid volume remains normal.

The antenatal management of hydronephrosis and the management of pregnancies with severe oligohydramnios are discussed in detail separately. (See "Fetal hydronephrosis: Etiology and prenatal management", section on 'Prenatal management' and "Oligohydramnios: Etiology, diagnosis, and management in singleton gestations", section on 'Prognosis and counseling by etiology'.)

POSTNATAL EVALUATION

Diagnosis — Ultrasonography confirms the diagnosis of megaureter. If an antenatal diagnosis is made, a postnatal ultrasound is obtained to confirm the presence of megaureter (image 2 and image 3). In our practice, we perform postnatal ultrasonography within the first few weeks of life for infants with unilateral megaureter and within 24 to 72 hours for those with signs of possible lower urinary tract obstruction (eg, posterior urethral valves [PUV]) on prenatal ultrasound, including bilateral hydronephrosis, bilateral ureteral dilation and/or dilated bladder, or thickened bladder wall (algorithm 1). For patients with any of these findings, we start continuous prophylactic antibiotics until a voiding cystourethrogram (VCUG) is obtained to evaluate for PUV and/or significant reflux.

Ultrasound findings consistent with primary megaureter include:

●Megaureter – Megaureter is defined as ureter diameter >7 mm in an individual between >30 weeks gestation and 12 years of age. In many cases of primary megaureter, the distal ureter is more dilated more than the proximal ureter or renal collecting system. The ureter may be tortuous.

It is important to identify the ureter's origin and insertion into the bladder to help differentiate it from bowel and from an ectopic ureter.

●Hydronephrosis – Megaureter usually presents as hydroureteronephrosis (dilation of both the renal pelvis and ureter). Less frequently, megaureter can occur without hydronephrosis or dilation of the upper collecting system. Ultrasound examination should be performed after the first two days after birth (preferably at one week of age or later) because hydronephrosis may not be detected, due to physiologic volume depletion and relative oliguria. The severity of hydronephrosis can be graded by the Society for Fetal Urology system (image 4) and/or the newer urinary tract dilation classification system (figure 4). (See "Postnatal evaluation and management of hydronephrosis", section on 'Postnatal ultrasound' and "Postnatal evaluation and management of hydronephrosis", section on 'Severity of hydronephrosis'.)

●Normal bladder size – A normal bladder size distinguishes primary megaureter from secondary megaureter (due to lower urinary tract obstruction, eg, neurogenic bladder, PUV, or prune-belly syndrome). Ultrasound findings suggesting lower urinary tract obstruction include a dilated bladder and/or increased thickness and trabeculation of the bladder wall.

Further evaluation — Further evaluation consists of a VCUG and, possibly, diuretic renogram to determine the type of megaureter (eg, refluxing or obstructed), which guides the management approach (algorithm 1) [9,10]. (See 'Classification' above and 'Postnatal management' below.)

●VCUG – A VCUG must be performed to detect reflux and any evidence of urethral obstruction (eg, PUV in males); this is particularly important for infants with bilateral megaureters. If severe reflux is present and the ureter drains poorly, the megaureter is likely a refluxing, obstructed type.

●Diuretic renography – If no reflux is detected on VCUG and the hydronephrosis is severe (Society for Fetal Urology grade 4 or urinary tract dilation category 3), diuretic renography is used to detect relative renal function in each kidney and the presence of urinary tract obstruction (image 5). The results differentiate between the nonrefluxing, obstructed megaureter and the nonrefluxing, nonobstructed type.

Diuretic renography consists of a renal scan and administration of a diuretic. In our institution, we use 99mTc-mercaptotriglycylglycine (MAG-3 or MAG3) as a radiotracer and furosemide as the diuretic (MAG3 furosemide renogram). This study measures the drainage time from the renal pelvis (referred to as washout) and assesses each individual kidney's relative renal function. For patients with a primary megaureter, a delayed washout curve is difficult to interpret (in contrast with ureteropelvic junction obstruction (UPJO), in which delayed washout is a more reliable indicator of obstruction). For the diuretic renogram to be most reliable, regions of interest over the kidney, ureter, and a combination of the two to assess drainage should be assessed. (See 'Asymptomatic patients' below and "Postnatal evaluation and management of hydronephrosis", section on 'Diuretic renography'.)

A more complete description of diuretic renography is found separately. (See "Postnatal evaluation and management of hydronephrosis", section on 'Diuretic renography'.)

Differential diagnosis — Imaging studies differentiate primary megaureter from other causes of hydronephrosis, including:

●UPJO – In UPJO, ultrasonography demonstrates dilation of the renal pelvis but not the ureter. The lack of ureter dilation distinguishes UPJO from primary megaureter, in which both the renal pelvis and ureter are dilated. (See "Congenital ureteropelvic junction obstruction", section on 'Diagnosis'.)

●PUV – In PUV, ultrasonography demonstrates a dilated bladder and/or increased thickness and trabeculation of the bladder wall, as well as a dilated posterior urethra (keyhole sign). These findings distinguish PUV from primary megaureter, in which the bladder size is normal. On VCUG, a dilated and elongated posterior urethra confirms the diagnosis of PUV. (See "Clinical presentation and diagnosis of posterior urethral valves", section on 'Diagnosis'.)

●Ureterocele – On ultrasonography, ureterocele is seen as a well-defined intravesical mass in the posterior portion of the bladder. This finding distinguishes it from primary megaureter. (See "Ureterocele", section on 'Diagnosis and evaluation'.)

POSTNATAL MANAGEMENT — Management options include surgical repair versus conservative medical management. In general, postnatal management decisions are determined by the presence or absence of reflux and/or obstruction, as outlined in the algorithm (algorithm 1).

There are no randomized trials that provide evidence for the optimal management of primary megaureter in infants and children. The following discussion reflects common practice and is based on observational studies and the experience of experts in the field.

Management options

Surgical management — Surgical treatment of the obstructed megaureter consists of excision of the distal obstructive segment, tapering of the dilated ureter, and reimplantation into the bladder using a reflux prevention technique (movie 1). In some cases, a temporary cutaneous ureterostomy is needed to allow for the caliber of the ureter to decrease to a more normal size. An alternative approach to reconstruction in the small baby is creation of a simple, refluxing ureteral reimplantation to avoid upper tract diversion [11]. The success rate of these procedures is determined by decreased ureteral and renal dilation on the ultrasound [12,13].

Several case series suggest that high-pressure balloon dilation or prolonged ureteral stenting may be a promising approach to treat primary obstructive megaureter in neonates or infants, in whom surgical reconstruction is more challenging [14-17]. Further studies with a larger number of patients are needed to confirm the long-term effectiveness and safety of this technique.

Medical management — Conservative medical management typically consists of antibiotic prophylaxis with ongoing monitoring [8].

●Antibiotic prophylaxis – We suggest antibiotic prophylaxis for all infants and children with:

•Refluxing megaureter – Suggested for this group because of the high risk of urinary tract infection due to urinary stasis [4].

•Severe nonrefluxing megaureter – Severe nonrefluxing megaureter is defined as grade 3 and 4 hydronephrosis by Society for Fetal Urology criteria or urinary tract dilation category 3. We also give attention to treating physiologic phimosis in boys.

For infants younger than two months, we use amoxicillin (10 to 15 mg/kg orally once daily). After two months of age, we switch to trimethoprim-sulfamethoxazole (2 to 3 mg/kg trimethoprim component orally once daily, maximum 80 mg/dose) or nitrofurantoin (1 to 2 mg/kg orally once daily, maximum 100 mg/dose). (See "Postnatal evaluation and management of hydronephrosis", section on 'Antibiotic prophylaxis'.)

For children with severe nonrefluxing megaureter, antibiotic prophylaxis is supported by observational evidence from a registry study and case series and by indirect evidence from children with hydronephrosis (see "Management of vesicoureteral reflux", section on 'Antibiotic prophylaxis'). In the registry study, children with megaureter had a nearly threefold increased risk of urinary tract infection compared with children with less severe hydronephrosis without megaureter and the risk increased with increasing ureteral diameter [18]. In this cohort, antibiotic prophylaxis was associated with lower rates of urinary tract infection (hazard ratio [HR] 0.5, 95% CI 0.28-0.87). In a case series of children with nonrefluxing megaureter (severity not defined), febrile urinary tract infections occurred in 12 percent of those treated with antibiotic prophylaxis, compared with 45 percent of those who were not treated [19]. The optimal duration of prophylaxis has not been established. In most published case series, antibiotic prophylaxis was given routinely through the first one to two years of life [3,4,6]. In our practice, we continue antibiotic prophylaxis until the patient is toilet trained because of the increased risk of urinary tract infection; this strategy seems prudent, especially in cases of severe megaureter. (See 'Asymptomatic patients' below.)

●Monitoring – Children are followed by annual renal ultrasonography to monitor renal growth and hydroureteronephrosis.

Nonrefluxing megaureter — In nonrefluxing megaureter, the choice between surgery and medical management is based on the presence of signs and symptoms and evidence of impaired renal function.

Asymptomatic patients — Most patients with asymptomatic nonrefluxing megaureter can be managed medically, with close monitoring (algorithm 1).

●Nonobstructed, nonrefluxing – Asymptomatic patients with nonrefluxing, nonobstructed megaureters and normal split renal function based on diuretic renography can be managed medically with close monitoring. In our practice, we prescribe antibiotic prophylaxis for more severe cases (Society for Fetal Urology hydronephrosis grade 3 and 4 or urinary tract dilation grade 3) until the child is toilet trained. (See 'Medical management' above.)

Monitoring consists of serial ultrasonography to monitor renal growth and hydroureteronephrosis. Our protocol is:

•Ultrasounds at least once each year until age three to five. If the megaureter remains stable, ultrasound evaluation continues at longer intervals (every other year for school-aged children and once every five years in adolescence) until resolution.

•If the megaureter and/or hydronephrosis worsens, we perform diuretic renography to assess overall renal function and possible obstruction. A >10 percent decrease in renal function is an indication for surgery.

•Surgical intervention is performed in patients who develop symptoms, calculi, recurrent infection, hematuria, or a decrease in the function of the affected kidney based on diuretic renography.

This conservative medical management is warranted because, in 80 to 90 percent of cases, hydroureteronephrosis resolves spontaneously without renal function impairment (image 5) [3,5,6,9,10,20,21]. Even severe hydroureteronephrosis can resolve spontaneously in some cases, although the time for resolution is longer [3-5]. In one study, infants with ureteral dilation >14 mm were more likely to require surgical intervention (HR 7.8, 95% CI 2-31) [22].

In patients who are initially managed conservatively, 15 to 20 percent ultimately require surgical intervention [3,4,20,23]. Indications for surgery are an increase in hydronephrosis, decreasing renal function on the affected side, or symptoms (recurrent urinary tract infections, pyelonephritis, persistent flank pain, calculi, or hematuria); any of these features suggest clinically significant obstruction (picture 1).

●Obstructed – Surgical correction should be performed in patients with obstructive lesions, which are identified by increasing hydroureteronephrosis and/or the presence of a prolonged diuretic renographic drainage pattern. Surgical correction of obstructed megaureters improves renal drainage, as detected by a reduction in hydroureteronephrosis on ultrasound [12,13].

This approach is supported by the following case series [4,24]:

•In a study of 49 patients, spontaneous resolution occurred in 80 percent of nonobstructive, nonrefluxing megaureter but only 20 percent in those who demonstrated an obstructive or partial obstructive diuretic renographic pattern [4]. Of the 16 patients with an obstructive or partially obstructive lesion, nine underwent surgical correction. The long-term outcome for kidney function was excellent, except for patients who already had renal abnormalities (eg, renal hypoplasia and dysplasia) and decreased renal function detected during the neonatal period.

•In a second case series of 75 patients with primary megaureter diagnosed between 1990 and 2005, surgical repair was performed on 34 of 88 primary ureters because of symptomatic disease or decreased renal function associated with massive dilation and obstruction [24]. Of the remaining patients who were managed conservatively with observation, subsequent complete resolution was documented in 47 of the remaining 54 ureters (87 percent). In this cohort, multivariate analysis showed that perinatal presentation and a nonobstructive pattern on diuretic renography were associated with spontaneous resolution. In contrast, the grade of hydronephrosis was not predictive of spontaneous resolution.

Symptomatic patients — We suggest surgical correction for most children with nonrefluxing megaureter who present with signs or symptoms suggesting obstruction. Obstruction may be detected on diuretic renography or diagnosed clinically based on suggestive symptoms (flank pain) or other concerning findings (eg, recurrent urinary tract infections, pyelonephritis, calculi, hematuria, or declining kidney function). Symptoms almost always resolve after surgical correction, and the long-term outcome for kidney function is excellent [23,25]. Children with infrequent or equivocal symptoms may be followed with observation as long as there is no evidence of impaired kidney function.

Refluxing megaureter

●Nonobstructed – Patients with refluxing, nonobstructed megaureter usually have moderate to severe vesicoureteral reflux (eg, grade IV to V vesicoureteral reflux). Management of these patients involves antibiotic prophylaxis and monitoring, with surgery for selected patients, as discussed separately. (See "Management of vesicoureteral reflux", section on 'Grades III to V'.)

●Obstructed – Patients with refluxing, obstructed megaureter typically have ectopic ureters that enter into the bladder neck or urethra; these patients are managed with surgery. Patients without ectopic ureters are generally managed with observation and antibiotics if they are asymptomatic and progress to surgery if they develop symptoms or have progressive ureteral dilation. (See "Ectopic ureter", section on 'Management'.)

OUTCOME — The long-term outcome of primary megaureter is generally excellent [4,10].

●Most cases of nonobstructive, nonrefluxing megaureter will spontaneously resolve (image 5). (See 'Nonrefluxing megaureter' above.)

●The outcome of surgical correction for obstructed lesions is excellent, with success rates greater than 90 percent (picture 1). (See 'Surgical management' above.)

●Outcome for either medical or surgical management of refluxing megaureter (ie, grade III to V vesicoureteral reflux) is also excellent. (See "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Natural history' and "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Kidney scarring' and "Management of vesicoureteral reflux".)

●Poor renal outcome appears to be due to the concomitant presence of congenital renal abnormalities (eg, renal hypoplasia and dysplasia) rather than as a consequence of primary megaureter, except in the setting of high-grade or worsening obstruction [4].

SUMMARY AND RECOMMENDATIONS

●Definition and classification

•Primary megaureter is defined as a ureter that is >7 mm in diameter and is caused by a functional or anatomical abnormality that involves the ureterovesical junction. It is classified based on the presence of reflux or obstruction into four categories (nonrefluxing, nonobstructed; nonrefluxing, obstructed; refluxing, nonobstructed; and refluxing obstructed). (See 'Introduction' above and 'Classification' above.)

•Secondary megaureter results from lower urinary tract obstruction (bladder or urethra). Causes of secondary megaureter (eg, posterior urethral valves [PUV], myelomeningocele/neurogenic bladder, prune-belly syndrome) are discussed separately. (See "Clinical presentation and diagnosis of posterior urethral valves" and "Myelomeningocele (spina bifida): Urinary tract complications" and "Prune-belly syndrome".)

●Clinical presentation – Primary megaureter is usually identified on prenatal ultrasound. Postnatal presentation can occur at any age with symptoms due to urinary tract infection, hematuria, abdominal pain and/or mass, or uremia. (See 'Clinical presentation' above.)

●Prenatal management – Fetuses with primary megaureter are managed expectantly as long as the amniotic fluid volume remains normal. Monitoring and management are discussed separately. (See "Fetal hydronephrosis: Etiology and prenatal management", section on 'Prenatal management'.)

●Postnatal evaluation – Infants with megaureter identified on prenatal ultrasound should be reevaluated after birth. For those with unilateral megaureter, the postnatal ultrasound should be performed within the first few weeks of life. For those with any signs of lower urinary tract obstruction (bilateral involvement, dilated bladder, or thickened bladder wall), the postnatal ultrasound should be performed within 24 to 72 hours after birth and antibiotic prophylaxis should be initiated pending further evaluation (algorithm 1).

•Diagnosis – The diagnosis of megaureter is defined as ureter diameter >7 mm on renal ultrasound, with normal bladder size (image 2). Most patients also have hydronephrosis (hydroureteronephrosis). (See 'Diagnosis' above.)

•Further evaluation – After the diagnosis of megaureter is made, further evaluation determines the type of megaureter (eg, refluxing, obstructed), which guides management. (See 'Further evaluation' above.)

-Voiding cystourethrography (VCUG) is performed in all patients with megaureters to detect the presence or absence of vesicoureteral reflux.

-Diuretic renography (renal scan and administration of a diuretic) is used to detect urinary tract obstruction. It is performed in cases with no reflux on VCUG but with severe hydronephrosis (Society for Fetal Urology grade 4 or urinary tract dilation category 3).

•Differential diagnosis – Imaging studies differentiate primary megaureter from other causes of hydronephrosis, including ureteropelvic junction obstruction (UPJO), PUV, and ureterocele. (See 'Differential diagnosis' above.)

●Management – Postnatal management of primary megaureter depends on the presence of obstruction and reflux (algorithm 1):

•Nonrefluxing, nonobstructed – In asymptomatic patients with nonrefluxing, nonobstructed megaureters, we suggest nonoperative management (Grade 2C). In most cases, hydroureteronephrosis resolves spontaneously without renal function impairment (image 5). Nonoperative management includes monitoring with annual ultrasounds for all such patients, with diuretic renography for those with worsening megaureter and/or hydronephrosis. (See 'Asymptomatic patients' above.)

We also suggest prophylactic antibiotics for more severe cases (Society for Fetal Urology hydronephrosis grade 3 and 4 or urinary tract dilation category 3) (Grade 2C), which are continued until the child is toilet trained. Surgery is indicated if there is subsequent development of symptoms, or evidence of obstruction or impaired renal function. (See 'Asymptomatic patients' above.)

•Nonrefluxing, obstructed – For most patients with symptomatic, nonrefluxing, obstructed megaureters, we suggest surgical intervention rather than nonoperative management (Grade 2C). Obstruction may be detected on diuretic renography or diagnosed clinically based on suggestive symptoms (flank pain) or other concerning findings (eg, recurrent urinary tract infections, pyelonephritis, calculi, hematuria, or declining kidney function). Patients with equivocal symptoms may be followed with observation as long as there is no evidence of impaired kidney function. (See 'Symptomatic patients' above.)

•Refluxing, nonobstructed – Management of patients with refluxing, nonobstructed megaureter involves antibiotic prophylaxis and monitoring, with surgery for selected patients, as discussed separately. (See 'Refluxing megaureter' above and "Management of vesicoureteral reflux".)

•Refluxing, obstructed – Patients with refluxing, obstructed megaureter typically have ectopic ureters that enter into the bladder, neck, or urethra. They are typically managed with surgery, as discussed separately. (See "Ectopic ureter", section on 'Management'.)