Chapter 18: THE FETAL GENITOURINARY SYSTEM

The fetal kidneys begin developing within the pelvis at approximately 7 weeks of gestation from the metanephric mesoderm and the ureteric bud. The metanephric tissue develops into the nephrons of the kidney, and the ureteric bud differentiates into the collecting tubules, calyces, pelvis, and ureter. Between 7 and 11 weeks, as the fetal body grows in length, the kidneys ascend to their permanent position in the flank due to disproportionate growth of more caudal structures.¹

Initially, the kidney is made up of several loosely connected lobes, each with a thin cortex. During the second trimester the lobes fuse, becoming less distinct, and the cortex thickens, leaving the kidney with a lobular contour that persists for several years after birth.^1,2 The kidneys begin to excrete urine at approximately 10 to 11 weeks of gestation, and from this age onward urine production increases progressively.

By the second trimester the kidneys become the major contributor to the amniotic fluid volume.^3,4 Adequate amniotic fluid volume is necessary for normal fetal pulmonary and skeletal development because it provides space for fetal growth and movement. Therefore, a functioning urinary tract must be present for the lungs and skeleton to develop normally.^{5, 6, and 7}

Using transvaginal ultrasound, normal fetal kidneys can first be seen as early as 9 weeks of gestation and should always be visible by the late first or early second trimester. With transabdominal scanning, the kidneys may first be visible at 13 to 14 weeks of gestation and are seen in most patients by 16 to 18 weeks (Figure 18-1). Delayed visibility may occur when factors such as maternal obesity or large uterine fibroids limit the fetal survey. The fetal bladder may be seen as early as 11 weeks with transvaginal scanning and should be visible transabdominally by 16 weeks in virtually all patients.^8,9

The incidence of genitourinary anomalies at birth is 0.2% to 0.6%.^{10, 11, and 12} Genitourinary anomalies comprise approximately one-fourth of all congenital structural anomalies.¹² Anomalies of the genitourinary tract result from arrested development early in organogenesis, failure of normal ascent, obstruction of the collecting system or bladder outlet, and abnormal formation of renal tubules. These anomalies are most often isolated but may also occur in association with, or may cause, other fetal structural abnormalities. Associations between genitourinary and other organ system anomalies occur in a broad variety of inherited or sporadic syndromes, including chromosomal abnormalities.^4,5,13,14 In addition, urinary tract abnormalities that decrease urine production cause oligohydramnios, which may secondarily cause deformities involving other parts of the fetus. In particular, when severe oligohydramnios is present before 20 weeks of gestation, pulmonary hypoplasia; facial abnormalities, including flattened nose and low-set ears; and club feet or other limb positional abnormalities may result.¹⁵

Prenatal sonography can identify and characterize many anomalies of the genitourinary system. Ultrasound performed in the second and third trimesters can detect at least 80% to 85% of genitourinary anomalies.^11,16 Prenatal diagnosis permits antenatal counseling and prompt postnatal evaluation and treatment, thus avoiding the therapeutic delays that, before the availability of ultrasound, often led to impairment or loss of renal function.¹⁷

Failure of development of the ureteric bud will lead to renal agenesis. Renal agenesis may be unilateral or bilateral. Unilateral agenesis occurs in approximately 0.3 per 1000 births and has an excellent prognosis. On prenatal ultrasound no kidney is seen in the renal fossa on the affected side and the contralateral kidney is large for gestational age. Color Doppler interrogation of the abdominal aorta will demonstrate a renal artery on one side and no renal artery on the other. It is important not to mistake the ipsilateral adrenal, which may be flattened or "lying down," for a kidney (Figure 18-2).¹⁸ This error is avoided by recognizing that the adrenal gland does not have central sinus echoes and does not have a reniform shape in the longitudinal plane. It is also important to scan the fetal pelvis to be sure the kidney is truly absent rather than in an ectopic location.^19,20

Bilateral renal agenesis is a lethal anomaly in which there is failure of development of both kidneys. This condition occurs in approximately 1 to 4 per 10,000 births, with a male to female ratio of 2.5 to 1. When this anomaly is present, there is severe oligohydramnios from the early to mid-second trimester onward. Bilateral renal agenesis, together with the fetal deformities resulting from oligohydramnios—pulmonary hypoplasia, abnormal facies, and limb position abnormalities—has been termed Potter syndrome.¹⁵ The neonate with bilateral agenesis typically dies shortly after birth from pulmonary hypoplasia. Recurrence in subsequent pregnancies is rare.

Sonographic diagnosis of bilateral agenesis is made on the basis of severe oligohydramnios and nonvisualization of the kidneys and urinary bladder (Figure 18-3). Careful scanning is required before making the diagnosis because absence of surrounding amniotic fluid degrades the sonographic image. Other sonographic findings often seen with bilateral renal agenesis include dolichocephaly and a small thorax, both secondary to uterine compression from the absence of amniotic fluid.^21,22

If one or both kidneys develop but fail to ascend normally into the renal fossa, one or both will ultimately reside in an ectopic location. This anomaly occurs in about 1 per 1200 births. The most common ectopic kidney is a pelvic kidney. Less commonly, a horseshoe kidney forms, in which the 2 kidneys are fused at their lower poles and ascend partially, such that their axes are altered and their lower poles extend across the midline of the lower abdomen. Occasionally, one kidney is crossfused to the lower pole of the contralateral kidney. Other ectopic kidneys, such as thoracic kidneys, are extremely rare.^{19, 20, and 21}

The sonographic findings with a pelvic kidney include a kidney in the pelvis adjacent to the urinary bladder and an empty renal fossa with a flattened adrenal gland (Figure 18-4).^{19, 20, and 21} The pelvic kidney is at increased risk for urinary obstruction, and therefore hydronephrosis may be seen.²³ With crossfused ectopia, one renal fossa will be empty and the contralateral kidney will appear very long and may be unusual in shape.²¹ The lower moiety may be hydronephrotic or have cystic dysplasia secondary to obstruction.²⁴

Sonographically, the location of horseshoe kidneys is lower in the abdomen, and the lower poles are displaced medially. Renal parenchyma may be seen extending across the midline in front of the fetal spine (Figure 18-5).²¹ These kidneys also have an increased incidence of obstruction and may have cystic dysplasia.²⁵

Dilatation of the fetal renal collecting system is the most common fetal abnormality detected by antenatal sonography. It can result from obstruction of the urinary tract, vesicoureteral reflux, or deficient musculature in the walls of the urinary tract and abdomen (prune belly syndrome). Urinary tract obstruction occurs most often at the level of the ureteropelvic junction but may also occur in the ureter, at the ureterovesical junction, or at the bladder outlet.

When fluid is seen in the intrarenal collecting system by ultrasound, it is important to determine whether it represents hydronephrosis or is merely the small amount of fluid often seen in the normal renal pelvis (and the trace amount of fluid occasionally seen in calyces) during the second and third trimesters. Hydronephrosis should be diagnosed when there is significant caliectasis or the anteroposterior (AP) diameter of the renal pelvis, measured on a transverse view through the kidney, is at least 7 mm at 16 to 20 weeks or at least 10 mm after 20 weeks of gestation (Figure 18-6). To avoid missing cases of evolving hydronephrosis, it is prudent to label a kidney with a renal pelvis of 4 to 6 mm at 16 to 20 weeks or of 5 to 9 mm after 20 weeks as possibly hydronephrotic and to follow the case in utero and postnatally. These criteria are based on studies that have shown that postnatal prognosis is related to prenatal AP diameter of the renal pelvis and the presence of caliectasis. The larger the AP diameter of the renal pelvis, the more likely it is that the fetus will need postnatal medical or surgical treatment. When the AP measurement is less than 10 mm and no calyceal dilatation is seen, approximately 10% of fetuses will prove to have vesicoureteral reflux after birth and a small number will have urinary obstruction. With an AP measurement of 10 mm or greater, the majority of fetuses will require medical or surgical intervention for urinary obstruction or vesicoureteral reflux.^{26, 27, 28, 29, 30, 31, and 32}

When hydronephrosis is diagnosed, it is important to examine the contralateral kidney because renal anomalies are often bilateral. The ureters and bladder should be carefully evaluated, looking for ureteral dilatation, bladder distention, and urethral dilatation, particularly if the hydronephrosis is bilateral. In addition, amniotic fluid volume should be assessed, and a careful search made for other fetal anomalies.²¹

When hydronephrosis is diagnosed in the second trimester, the possibility of a chromosomal abnormality, especially trisomy 21, must be entertained. Up to one-fourth of fetuses with trisomy 21 have mild hydronephrosis in the second trimester as compared with 2% to 3% of normal fetuses. With isolated hydronephrosis in the absence of other abnormalities, the likelihood of trisomy 21 is approximately 1 in 340. The likelihood of a chromosomal abnormality is especially high when, in addition to hydronephrosis, the femur is small or there is a cardiac or gastrointestinal abnormality.^33,34

An obstructed kidney is at risk for becoming dysplastic. The earlier and more complete the obstruction, the greater the likelihood and severity of dysplasia. Complete ureteral obstruction before 10 weeks results in a multicystic dysplastic kidney. When obstruction occurs after 10 weeks or is incomplete, the dysplastic kidney maintains a more reniform shape and is characterized sonographically by a thin echogenic renal parenchyma, often with small cysts. Sometimes hydronephrosis is present, in which case there is a dilated collecting system surrounded by abnormal-appearing renal tissue. In other cases, the dysplastic kidney is small and echogenic, with little or no fluid in the renal pelvis (Figure 18-7). With any dysplastic kidney, renal function is poor or absent and will not improve, even if obstruction is corrected.^21,35

Ureteropelvic junction (UPJ) obstruction is the most common cause of hydronephrosis in the neonate and affects males more than twice as often as females. It is a functional obstruction and is bilateral in 30% of cases. On ultrasound, a dilated renal pelvis is seen, with or without dilated calyces (Figure 18-8). The ureters are not dilated, and the amniotic fluid is usually normal.^{17,32,36, 37, and 38}

Most kidneys with UPJ obstruction do not become dysplastic. Dysplasia does occur, however, in a minority of cases, typically those with severe or early-onset obstruction.^17,32,36 When dysplasia does occur, it is most often the hydronephrotic form, although it may evolve into the nonhydronephrotic variety. Development of dysplasia in a kidney with UPJ obstruction can be diagnosed when the parenchyma becomes abnormally echogenic or cystic.

Vesicoureteral reflux, or reflux from the bladder into the ureter, results from an abnormal relationship between the distal ureter and the bladder wall. Normally, the ureter traverses the bladder wall at a shallow angle, leading to a long intramural segment of ureter that acts as a valve preventing reflux. When the ureter has a steep, short course through the bladder wall, reflux may occur. This abnormality is much more common among males than females and is often bilateral. It often resolves spontaneously within the first 1 to 2 years of life. Reflux that does not resolve spontaneously or is very severe at birth can be corrected surgically.^28,29,39

The sonographic findings of vesicoureteral reflux include hydronephrosis and hydroureter (Figure 18-9).²¹ In some cases, the hydronephrosis and hydroureter are present intermittently, with emptying and refilling every few minutes. In severe cases, the ureter may be markedly dilated and tortuous. Care must be taken not to mistake such a ureter for a dilated bowel loop. This error can be avoided by following the dilated ureter proximally to the renal pelvis and distally to the bladder.

Primary megaureter is a functional obstruction at the distal ureter, resulting from an aperistaltic distal ureteral segment. The prognosis is good. In mild cases no intervention is required, and in more severe cases corrective surgery can be performed.^40,41

The sonographic findings are hydronephrosis and hydroureter. The dilated ureter may be quite large, filling much of the lower abdomen, and may demonstrate peristalsis.²¹ Because the combination of hydronephrosis and hydroureter is seen with both reflux and megaureter, the distinction between the two usually cannot be made in utero but must await postnatal evaluation with voiding cystourethrography and intravenous pyelography.

Bladder outlet obstruction occurs almost exclusively in males, most often as a result of posterior urethral valves. It may also occur with urethral atresia or caudal regression syndrome, both of which occur in males and females.^{42, 43, 44, 45, and 46} On ultrasound, regardless of cause, the urinary bladder is dilated and may have a thick wall. The posterior urethra may be dilated and appear as a projection from the bladder base, particularly in cases of posterior urethral valves (Figure 18-10). The ureters are usually dilated. The kidneys have a variable appearance depending on the presence and extent of dysplasia. Possible appearances include hydronephrosis with normal-appearing renal parenchyma, hydronephrosis with echogenic or cystic renal parenchyma, or small shrunken kidneys with echogenic parenchyma. The kidneys may also appear normal or only mildly hydronephrotic when the urinary tract ruptures, thus decompressing itself into the perinephric space or the abdomen. When urine spills into the peritoneal cavity, it is called urine ascites (Figure 18-11). Oligohydramnios is often present, particularly when the bladder outlet obstruction occurs early in gestation and is severe.²¹ Some cases of posterior urethral valves present in the third trimester after a normal second trimester ultrasound. Other cases may not present until early childhood.⁴⁴

The prognosis with bladder outlet obstruction is variable and is best predicted prenatally on the basis of amniotic fluid volume: the lower the fluid volume, the worse the prognosis. In particular, the prognosis is dismal when there is severe oligohydramnios. In these cases, neonatal death may occur early from pulmonary insufficiency or later from renal insufficiency secondary to dysplasia.^43,44

Prenatal treatment of bladder outlet obstruction has been successfully employed in a number of fetuses with this condition. Treatment involves creating a passageway for urine from the urinary tract to the amniotic cavity, by either percutaneously placing a shunt catheter from the fetal bladder to the amniotic fluid space (Figure 18-12) or open hysterotomy and fetal surgery to create bilateral ureterostomies.^47,48 Treatment can be considered in cases that meet the following selection criteria: (1) presence of oligohydramnios; (2) previable gestational age; (3) normal-appearing renal parenchyma; (4) no other lethal anomalies and a normal karyotype; and (5) normal renal function, as determined by biochemical tests performed on urine percutaneously aspirated from the fetal bladder. Although only a small fraction of fetuses with bladder outlet obstruction will meet these stringent criteria, treatment in those that do meet them may lead to an infant with adequate pulmonary and renal function.

There are two conditions that can potentially be confused with bladder outlet obstruction on ultrasound. Prune belly syndrome is a condition occurring mainly in males that is characterized by partial or complete lack of abdominal musculature and undescended testes. Megaureter megacystis is a condition in which there is massive vesicoureteral reflux, such that urine flows back and forth between the bladder and ureters. With both of these conditions, the sonographic findings include bilateral hydronephrosis and hydroureters, as well as a distended bladder. Unlike bladder outlet obstruction, the amniotic fluid volume is usually normal.^42,49

Duplication of the renal collecting system is a common abnormality that, unlike most urinary tract anomalies, is more common in females than males. In most cases, the duplication anomaly is unilateral.^50,51 When there is complete duplication of the ureter as well, the upper pole ureter often implants ectopically, in a site caudal and medial to normal, and this ureter is often obstructed, while the lower pole ureter inserts at the normal location and may reflux. When the upper pole ureter implants ectopically in the bladder, there may be a ureterocele (ectopic ureterocele) bulging into the bladder lumen.^50,51

The diagnosis of duplication can be made by ultrasound when there is hydronephrosis that differentially affects the upper and lower poles of the kidney. The hydronephrosis is most often limited to, or more severe in, the upper pole. The associated dilated ureter may also be seen, and occasionally an ectopic ureterocele will be seen in the urinary bladder (Figure 18-13). The dilated upper pole collecting system may mimic a cyst or hydronephrosis of the entire kidney.^21,50,52

Multicystic dysplastic kidney is a form of renal dysplasia that is thought to occur as a result of complete obstruction or atresia at the level of the renal pelvis and infundibulum (pelvoinfundibular atresia) or of the proximal ureter before 10 weeks of gestation. A multicystic dysplastic kidney is nonfunctional and comprises of noncommunicating cysts of various sizes that replace the normal renal parenchyma. It is generally larger than a normal kidney. Contralateral renal abnormalities are seen in 40% of cases, the most common of which is ureteropelvic junction obstruction.^21,53 When the multicystic dysplastic kidney is unilateral, the prognosis is excellent because the contralateral kidney will be compensatorily enlarged.⁵⁴ Rarely, multicystic dysplastic kidneys occur bilaterally. This is a fatal condition because it is functionally equivalent to bilateral renal agenesis.

On ultrasound, a multicystic dysplastic kidney appears as a mass in the renal fossa composed of multiple cysts of various sizes (Figure 18-14).²¹ Amniotic fluid volume is usually normal. The finding of low fluid volume should prompt a careful inspection of the contralateral kidney, with a search for obstruction, dysplasia, or agenesis.

Polycystic kidney disease may be inherited either as an autosomal recessive abnormality or as an autosomal dominant one. The autosomal recessive form manifests itself early in life, in many cases in utero. The autosomal dominant form typically manifests itself in the second or third decade of life, but in rare cases may be evident in utero.^{55, 56, 57, and 58}

Autosomal Recessive Polycystic Kidney Disease

Autosomal recessive polycystic kidney disease, previously termed infantile polycystic kidney disease, is an inherited disorder characterized by cystic dilatation of the renal tubules, often with associated hepatic fibrosis. The renal abnormality leads to impaired or absent renal function. This renal abnormality is usually evident in utero, but in some cases may not manifest itself until childhood. The age at presentation is related to the fraction of renal tubules that are affected. When 90% of renal tubules are involved, renal function is markedly impaired in utero and neonatal death is likely. In general, the degree of hepatic fibrosis is inversely proportional to the degree of renal involvement. As a result, the hepatic component of the disease mostly affects those cases that survive into childhood.^{59, 60, and 61}

With autosomal recessive polycystic kidney disease, the kidneys are enlarged but maintain their reniform shape. When the onset is prenatal, ultrasound will demonstrate large echogenic kidneys with enhanced through-transmission (Figure 18-15). Despite the name, cysts are not identifiable by ultrasound. The bladder is often absent, and severe oligohydramnios may be present as early as 16 weeks of gestation.²¹ In those cases with early prenatal onset, the syndrome is lethal because of pulmonary hypoplasia secondary to severe oligohydramnios. When renal impairment begins after birth, prenatal ultrasound often demonstrates enlarged echogenic kidneys, but there will be fluid in the bladder and normal amniotic fluid volume.^59,60

The finding of bilateral echogenic kidneys is not specific for autosomal recessive polycystic kidney disease. It may be seen with a number of other pathologic entities, including autosomal dominant polycystic kidney disease (see below) and various forms of renal dysplasia. It may also be a normal variant.^56,57 When echogenic kidneys are identified prenatally, it is important to look for the urinary bladder and assess the amniotic fluid volume. Follow-up prenatal scans and postnatal tests of renal function may provide additional information to distinguish a pathologic condition from a normal variant.

Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease most often presents in young adulthood but can rarely be seen prenatally. This syndrome is associated with multiple renal cysts, hypertension, and renal failure. Cysts are commonly seen in other organs, including the liver, spleen, and pancreas. In the rare cases that present in the fetus, the sonographic appearance of the kidneys may be similar to that of autosomal recessive polycystic kidney disease, with enlarged echogenic kidneys. Cysts may occasionally be seen in the kidneys, and amniotic fluid volume may be decreased.^{55, 56, 57, and 58}

Solid masses and isolated cysts may occur in fetal kidneys, although both are quite rare. The most common solid mass is a mesoblastic nephroma, which is a hamartoma of the kidney (Figure 18-16). Rarely, a Wilms tumor will be seen in the fetus.⁶² Isolated cysts, seen sonographically as anechoic round lesions in the kidney (Figure 18-17), must be distinguished from focal hydronephrosis, which most often affects the upper pole of a duplicated collecting system.

Megacystis

Megacystis is an anomaly in which there is ineffective emptying of the urinary bladder, leading to marked dilatation of the bladder. Megacystis occurs in females in association with deficient bowel peristalsis (megacystis microcolon) or in either sex due to a neurogenic bladder from a meningomyelocele.^42,47

Exstrophy

Failure of regression, or incomplete regression, of the cloacal membrane results in a spectrum of anomalies that ranges in severity from mild epispadius in males or labial separation in females, to cloacal exstrophy, a large defect in the lower anterior abdominal wall, bladder, and colon, with eversion of the bladder and distal colon. Cloacal exstrophy occurs sporadically and affects males twice as frequently as females.^{63, 64, 65, 66, and 67}

Intermediate in severity is exstrophy of the urinary bladder, in which there is a defect in the anterior abdominal and bladder walls, with eversion of the bladder. The symphysis pubis is splayed, and there are associated anomalies of the external genitalia, including labial separation and a bifid clitoris in females and epispadius in males.⁶⁸

On ultrasound, bladder exstrophy may be suspected when there is nonvisualization of a fluid-filled urinary bladder, especially if there is also a soft tissue mass on the surface of the lower abdominal wall, representing exposed bladder mucosa (Figure 18-18). In some cases, however, fluid can be seen in the urinary bladder despite its opening to the amniotic cavity, and the diagnosis may be difficult to make.⁶⁸

Ovarian Cysts and Masses

Cysts occasionally develop in the ovary of a female fetus. Most are follicular cysts, but corpus luteal cysts, theca lutein cysts, teratomas, and cystadenomas may also occur. A cyst may grow throughout gestation in response to high estrogen levels in the maternal serum that crosses the placenta. Cysts also predispose the ovary to torsion. On ultrasound, an ovarian cyst is a simple cyst in the lower fetal abdomen (Figure 18-19). It is indistinguishable from a mesenteric cyst, omental cyst, gastrointestinal duplication cyst, or hydrometrocolpos. Ovarian torsion can be diagnosed if there is an acute change in a previously identified ovarian cyst, with increase in size and development of echoes within the cyst (Figure 18-20).^{69, 70, 71, and 72}

Congenital solid ovarian masses are rare, most often being germ cell tumors. When present, they appear as solid masses in the lower abdomen.

Hydrometrocolpos

Hydrometrocolpos is a condition in which the uterus and vagina are distended by secretions due to obstruction from imperforate hymen, transverse vaginal septum, or vaginal or cervical atresia. When the dilated uterus and vagina form a large pelvic mass, they may cause hydronephrosis and hydroureter. The sonographic appearance of hydrometrocolpos is a cystic pelvic mass, often with low-level echoes, located posterior to the bladder and extending into the abdomen.⁷³ Because it is indistinguishable from other pelvic and lower abdominal cystic masses, precise diagnosis cannot be made until after birth.

Hydrocele

Collection of fluid between the layers of the tunica vaginalis in the scrotum is a hydrocele. It is easily diagnosed sonographically by identifying fluid within the scrotum, often outlining the testicles (Figure 18-21). Hydroceles may be seen in association with ascites. When present as an isolated finding, they are of little or no clinical significance.

Cryptorchidism

Cryptorchidism, or undescended testicle, can be detected sonographically by failure to visualize the testicle within the scrotum. The testicles may not fully descend until late in pregnancy, so this finding may be present in at least 10% of fetuses in the early to mid-third trimester. Its incidence at term is approximately 1%.⁷⁴ Although most often an isolated finding, it can be seen in variety of syndromes, including prune belly syndrome, Noonan syndrome, and trisomies 13, 18, and 21.

Ambiguous Genitalia

Ambiguous genitalia refers to external genitalia that are not clearly of either sex. This can result from abnormal hormone levels, as in congenital adrenal hyperplasia, transplacental passage of hormones, and true hermaphroditism (presence of both ovarian and testicular tissue). Anomalies of the external genitalia that are not hormonally mediated can also occur (eg, micropenis). These latter anomalies can be isolated; they may have associated urinary tract anomalies or chromosomal abnormalities; or they may occur as one component of a multiple malformation syndrome.⁷⁵ The sonographic features of ambiguous genitalia are a small phallus displaced downward between a splayed scrotum or labia (Figure 18-22).

Testicular Feminization

Testicular feminization is a condition characterized by female external genitalia in conjunction with a male karyotype (46,XY chromosomes). It results from a disorder in the androgen receptor that renders the body unable to respond to testosterone. Affected fetuses produce testosterone at levels higher than normal, but the hormone has no effect and the fetus fails to develop male features. Prenatal diagnosis can be made in conjunction with genetic amniocentesis when the sonogram demonstrates female external genitalia and amniocentesis demonstrates a male karyotype.⁷⁶