Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 403–415

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Ultrasound diagnosis of fetal renal abnormalities Tiran Dias, MD (Obs & Gyn), MRCOG (UK), MD-Research (London), Dip (Fetal Med) UK, Consultant Obstetrician and Gynaecologist a, *, Shanthi Sairam, MBBS, MRCOG b, Shanya Kumarasiri, MBBS a a b

Department of Obstetrics and Gynecology, District General Hospital, Ampara, Sri Lanka Fetal Medicine and Fetal Cardiology, Mediscan, Chennai, India

Keywords: prenatal diagnosis renal tract anomalies ultrasound

Development of the urogenital system in humans is a complex process; consequently, renal anomalies are among the most common congenital anomalies. The fetal urinary tract can be visualised ultrasonically from 11 weeks onwards, allowing recognition of megacystis at 11–14 weeks, which warrants comprehensive risk assessment of possible underlying chromosomal aneuploidy or obstructive uropathy. A mid-trimester anomaly scan enables detection of most renal anomalies with higher sensitivity. Bilateral renal agenesis can be confirmed ultrasonically, with empty renal fossae and absent bladder filling, along with severe oligohydramnios or anhydramnios. Dysplastic kidneys are recognised as they appear large, hyperechoic, and with or without cystic spaces, which occurs within the renal cortex. Presence of dilated ureters without obvious dilatation of the collecting system needs careful examination of the upper urinary tract to exclude duplex kidney system. Sonographically, it is also possible to differentiate between infantile type and adult type of polycystic kidney diseases, which are usually single gene disorders. Upper urinary tract dilatation is one of the most common abnormalities diagnosed prenatally. It is usually caused by transient urine flow impairment at the level of the pelvi-ureteric junction and vesico-ureteric junction, which improves with time in most cases. Fetal lower urinary tract obstruction is mainly caused by posterior urethral valves and urethral atresia. Thick bladder walls and a dilated posterior urethra (keyhole sign) are suggestive of posterior urethral valves. Prenatal ultrasounds cannot be used confidently to assess renal function. Liquor volume and echogenicity of renal

* Corresponding author. Tel.: þ94 632222261; Fax: þ94 632223928. E-mail address: [email protected] (T. Dias). 1521-6934/$ – see front matter Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bpobgyn.2014.01.009

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parenchyma, however, can be used as a guide to indirectly assess the underlying renal reserve. Renal tract anomalies may be isolated but can also be associated with other congenital anomalies. Therefore, a thorough examination of the other systems is mandatory to exclude possible genetic disorders. Ó 2014 Elsevier Ltd. All rights reserved.

Introduction Assessment of fetal anatomy during the second trimester using ultrasound scanning has now become standard practice in most antenatal care set-ups, thus permitting the diagnosis of most structural abnormalities in the fetus. Renal anomalies constitute about 20% of all congenital abnormalities [1,2]. As a result, prenatal identification of renal anomalies provides options for prospective parents as they significantly affect perinatal morbidity and mortality. Additionally, it also functions as a key mechanism in promoting early detection of conditions, which may otherwise present itself later on in life, conceivably with more advanced sequelae. In this chapter, we concentrate on ultrasound diagnosis of renal tract abnormalities. Embryology of the human kidney development The urogenital system develops from the mesodermal ridge (intermediate mesoderm) in the posterior wall of the abdominal cavity. During the stages of intrauterine life, three renal systems develop; namely the pronephros, mesonephros, and metanephros. The pronephros and mesonephros are transient excretory systems, and disappear without contributing to the permanent renal system. The mesonephric duct gives rise to some reproductive organs in male fetuses while degenerating in female fetuses. The metanephros appears in the 5th week of development and contributes to the metanephric mesoderm, forming the nephron units of the kidney. The ureteric bud arises from the mesonephric bud and forms the collecting system of the kidney, including the ureter, the renal pelvis, the major and minor calyces, and about 1–3 million collecting tubules. The cranial end of the ureteric bud comes into contact with the metanephric cell mass, and this induces the development of the metanephric mesoderm into the future nephron and the ureteric bud into the collecting system. The definitive kidney develops in the sacral region and ascends up into the renal fossa in the lumbar region as the embryo matures, and demonstrates differential growth of the abdominal wall. During weeks 4–7, the cloaca develops into the urogenital sinus anteriorly and the anal canal posteriorly. The developing mesonephric ducts drain into the upper part of the urogenital sinus, laying the foundation for the future bladder. This developing bladder is initially in communication with the allantois, but with progressive development of the anterior abdominal wall, the allantois disappears, leaving behind an obliterated thick fibrous tissue called the urachus, which connects the bladder apex to the umbilicus. It forms the medial umbilicus ligament in the adult. The developing bladder incorporates the mesonephric duct into its trigone, and posteriorly spaces out the two ureteric orifices appropriately. Subsequently the lower part of the urogenital sinus develops into the prostatic and membranous urethra. The external genital development differs significantly between the two sexes; hence, elaboration is beyond the scope of this review. The definitive kidney becomes functional by week 12, although they do not have any major excretory function as the placenta works as an excretory organ until birth. Urine production starts around 10 weeks of gestation, and is the major contributor to amniotic fluid from about 14 weeks of gestation. Nephrons continue to be formed up until the time of birth when they are about 1 million in number. The number of nephrons remains static while they grow in size during infancy. Normal ultrasonic imaging of fetal kidney Congenital abnormalities of the genitourinary tract, especially of the kidney and bladder, affect 3– 4% of the population [3]. The fetal kidneys contribute to the amniotic fluid volume from about 14

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weeks, and are essential for maintaining liquor volume throughout pregnancy. The presence of a structural, functional renal anomaly, or both, may result in oligohydramnios or anhydramnios, which may in turn affect pulmonary development. It is therefore necessary to establish the normalcy of the renal system as early as possible. The primary imaging modality used to visualise the fetal urogenital tract antenatally is ultrasound. Normal kidneys along with the adrenal glands may be visible in a scan from as early as 9 weeks. They are seen on either side of the fetal spine just below the level of the fetal stomach. The kidneys appear echogenic in the early weeks, and gradually become hypoechoic compared with the adjacent bowel and liver. It is recommended that the kidneys are seen in axial, sagittal and coronal planes (Fig. 1). The renal cortex appears echogenic compared with the medulla, and the renal pelvises are seen as anechoic spaces in the medial aspect in the transverse sections. In the third trimester, the pyramids can be differentiated from the cortex as it appears more hypoechoic. The kidneys grow as long as the pregnancy continues, and the size is directly proportional to the gestational age. Adrenal glands can be seen on the superior pole of the kidney. In the absence of kidneys in their normal positions in the renal fossa, the adrenals can occupy the renal fossa and mimic the renal structure. The fetal kidney should be seen in all fetuses in the anomaly scan, whereas it tends to be seen in 80% of the cases at 11 weeks and in 92% of cases at 13 weeks of gestation [4]. Many centres routinely visualise the renal arteries using colour Doppler as a part of the scan (Fig. 1). These can be seen as direct branches of the abdominal aorta in a posterior coronal view, just inferior to the origin of the superior mesenteric artery. Fetal ureters are not usually visible antenatally unless they are dilated. The fetal bladder can be visualised in the pelvis from 11–12 weeks of gestation, and persistent absence of the bladder should be considered as abnormal from 15 weeks [4,5]. Fetal urine production begins between 8–10 weeks of gestation. Oligohydramnios, however, cannot be found before 10 weeks of age, as amniotic fluid at this point of the gestation period is mainly formed by the secretions of the placenta, fetal membranes and skin. Abnormal renal development Renal agenesis Renal agenesis is the congenital absence of kidneys, and can be bilateral or unilateral. Bilateral renal agenesis is not compatible with life, and occurs in 0.1–0.3 per 1000 births. Isolated unilateral agenesis accounts for 1 in 1000 births, and is three times more common in males [6]. Renal agenesis can be an isolated finding, but is more commonly part of a syndrome and warrants a detailed anomaly scan to look for associated anomalies [7]. Various inheritance patterns exist in families with renal agenesis. The risk of bilateral renal agenesis in the fetus is thought to be around 1% if one parent has unilateral agenesis [8]. If renal agenesis is detected in the fetus, it warrants renal imaging in parents.

Fig. 1. (A) Transverse view of the normal renal pelvises at 20 weeks; and (B) demonstration of normal renal arteries by power Doppler at 20 weeks.

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The most common presentation in bilateral renal agenesis is anhydramnios, generally identified at the time of a routine mid-trimester anomaly scan. The fetal kidneys are not visualised in the renal fossa, and the bladder does not fill during the scan, with noticeably reduced or absent liquor from 16 weeks (produced by placenta in the first trimester). In general, if the fetal bladder is not visualised during the scan, it is recommended to repeat the scan after 30 mins to allow for an empty bladder to refill. Persistence of an empty bladder in the absence of demonstrable renal tissue and anhydramnios are all strong pointers to bilateral renal agenesis. The lack of recognisable renal arteries on colour Doppler would strongly support the suspicion of bilateral renal agenesis [9]. Additionally, the adrenal gland will show a linear appearance but can sometimes appear ovoid in certain scans, and can be mistaken for the kidney [10]. Proper visualisation of the renal fossa is restricted by factors such as severe oligohydramnios, maternal obesity, and the positioning of the bowel can also obscure the view. Therefore, it is essential to carefully evaluate the renal fossa for an accurate conclusion. Unilateral agenesis is three to four times more common than bilateral agenesis, and carries a better prognosis. On an ultrasound examination, the fetal bladder is usually seen to fill and empty normally with normal liquor volume. The contralateral kidney may appear hypertrophied, and usually functions normally. Cho et al. [11] showed that the ratio of antero-posterior to transverse renal diameter gives a better guide to the size of the contralateral kidney [11]. If the ratio is greater than 0.9, it is highly suggestive of absence of the other kidney, and has a sensitivity, specificity and accuracy of 100%. The identification or suspicion of unilateral or bilateral renal agenesis should always prompt a thorough search for other anomalies in the fetus, as the risk of associated anomalies or genetic syndrome may be as high as 30% (Table 1) [12]. Dysplastic kidneys A dysplastic kidney is a kidney that has abnormal development of the glomeruli and nephrons along with a disproportionately increased stroma [13]. Dysplastic kidneys are often of abnormal size, structure, or both, and are identified prenatally with or without cystic changes. The dysplasia is thought to be caused by altered interactions between the ureteric bud and the metanephric mesenchyme [14]. Nephrons are present in reduced numbers in dysplastic kidneys, leading to reduced renal function and abnormal connections with the collecting system, resulting in cyst formation. Although

Table 1 Unilateral or bilateral renal agenesis and some related single gene disorders. Syndrome (Gene)

Inheritance

Other anomalies

Acro–renal–ocular syndrome (SALL 4) Branchio–oto–renal syndrome (EYA1, SIX1) Ectrodactyly–ectodermal dysplasia–cleft syndrome (P63) Pallistere Hall syndrome (GLI3)

Autosomal dominant

Eye: unilateral/bilateral coloboma; Duane anomaly

Autosomal dominant

Ear anomalies: ear pits, microtia; anotia; auditory canal atresia; absent or hypoplastic ear ossicles; branchial cysts Ectrodactyly; ectodermal dysplasia; cleft palate

Autosomal dominant Autosomal dominant

Renal–coloboma syndrome (PAX2) Townes–Brocks syndrome (SALL1)

Autosomal dominant Autosomal dominant

Antley–Bixler syndrome (FGFR2)

Autosomal recessive

Fraser syndrome (FRAS1)

Autosomal recessive

Smith–Lemli-Opitz syndrome (DHCR7) Goltz–Gorlin syndrome (PORCN)

Autosomal recessive

Kallman syndrome (KAL1) Lenz microphthalmia (BCOR)

X-linked X-linked

X-linked

Imperforate anus; mesoaxial polydactyly; hypothalamic hamartoma Myopia; nystagmus; optic nerve coloboma Imperforate anus; external ear anomalies; deafness; thumb anomalies Craniosynostosis; bowing of ulna and femur; vertebral anomalies; thin ribs; ambiguous genitalia Cryptophthalmos; cutaneous syndactyly; ambiguous genitalia; malformed ears Toe syndactyly; growth retardation; cardiac and cerebral malformations; genital anomalies Focal dermal hypoplasia; variable limb defects; cardiac anomalies Hypogonadotropic hypogonadism; anosmia Microphthalmia; genital anomalies

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renal dysplasia has many underlying causes, such as genetic defects, lower urinary tract obstruction, and teratogens, most cases are sporadic, with a multifactorial etio-pathogenesis. Multicystic dysplastic kidneys often follow ureteric obstructions owing to improper canalisation at 8 weeks of gestation. Several genes have also been identified, but their precise roles in the development of the kidneys have not been well defined. Dysplastic kidneys have a characteristic appearance at the routine 20-week anomaly scan; they appear large and bright, usually with cystic spaces lining the cortex. Typically, the cysts are multiple, thin walled with no connections, randomly placed in the renal parenchyma, and form an irregular outlined kidney [14,15] (Fig. 2). In the presence of large cysts, the entire renal parenchyma seems to be filled with cysts, and the kidneys lose all signs of cortico-medullary differentiation. Rarely, dysplastic kidneys appear uniformly echogenic on ultrasound without cysts, and can be difficult to differentiate from normal kidneys. The renal pelvis and ureters are not seen, and the renal artery flow on Doppler cannot always be recorded. The degree of abnormality can be judged by assessing the size of the affected kidney with a normal kidney, the echogenicity compared with the surrounding organs, the liquor volume (even though this is primarily dependent on the function of the contra lateral kidney), and the presence and number of cysts. Furthermore to establish a diagnosis, family history, ultrasound of parents’ kidneys, genetic referral, and karyotyping, for example, should be considered. The presence of any associated anomaly in the fetus should also be noted. Dysplastic kidneys are often associated with other syndromes such as VACTERL association, Meckel–Gruber syndrome, Bardet–Biedl syndrome, Fraser syndrome and CHARGE syndrome [12,15]. The outcome would obviously be dictated by the associated findings in these conditions. Most babies with isolated unilateral multicystic renal disease tend to have a good outcome [15]. The size and number of cysts in unilateral multicystic disease generally do not influence the outcome, although the main prognostic factor is the contralateral kidney size and presence or absence of other anomalies [15]. Bilateral involvement is generally associated with severe oligohydramnios, and has a poor prognosis owing to the resultant pulmonary hypoplasia. The presence of significant associated anomalies or bilateral renal disease would create situations when the option to terminate the pregnancy would need to be discussed. In the case of perinatal death or if the parents elect to terminate the pregnancy, an expert postmortem should be carried out. If postmortem is declined, at least a needle biopsy of the kidney should be considered. Duplex kidney Duplex kidney system is one of the common renal tract anomalies often diagnosed postnatally [16]. It is characterised by duplication of collecting systems (duplex collecting systems) in which two pyelocaliceal systems are present in a single kidney with single or double ureters. Usually duplex system is unilateral and more common among females [17]. Prenatal diagnosis is possible with the presence of the following [17]; length of the kidney in the sagittal view greater than 95 percentile;

Fig. 2. Unilateral multicystic dysplastic kidney at 20-week scan.

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cystic-like structure surrounded by a rim of renal parenchyma in the upper pole of the kidney; kidney with two separate non-communicating renal pelvises; and dilated ureter usually draining the upper pole and echogenic cystic structure in the bladder (ureterocele). As most of the operators are not familiar with the duplex system, prenatal diagnosis is infrequent [17]. Therefore, presence of dilated ureters without obvious dilatation of the collecting system needs careful examination of the upper urinary tract to exclude duplex system. Polycystic kidney disease Infantile polycystic kidney disease Polycystic kidney diseases comprise two entities. Infantile polycystic kidney disease is also known as Potter type I, which has an autosomal recessive inheritance. It is the most common cystic disease in pregnancy, and carries a 25% risk in subsequent pregnancies [18]. This is a single gene disorder, and the abnormal gene is located in the short arm of chromosome 6 [18]. Prenatal diagnosis by first-trimester chorionic villous sampling can be offered to families at risk. Age of onset of this condition is varied and is subdivided into perinatal, neonatal, infantile and juvenile [19]. The pathology is mainly the presence of numerous small cysts of 1–2 mm size seen in the periphery of the kidney with normal renal pelvis and ureters [20]. The prenatal type is characterised by bilaterally enlarged and homogenously hyperechoeic kidneys, with or without oligohydramnios (Fig. 3). Ultrasonic features may not be apparent before 24 weeks, and serial examinations should be carried out. A concurrent finding of liver cysts, hepatic fibrosis, portal hypertension, and biliary duct hypoplasia may also be seen. The degree of clinical progression depends on the percentage of tubules involved and the degree of hepatic fibrosis. Kidneys are affected in earlier onset, and hepatic fibrosis is common in late onset polycystic kidney disease. Of the four sub-types of infantile polycystic kidney disease, the perinatal onset type is the most common, with renal failure occurring in utero, and 40–50% affected with hepatic fibrosis. Perinatal mortality is usually caused by pulmonary hypoplasia after severe oligo- or anhydramnios [18]. The scan findings tend to be bilaterally enlarged echogenic kidneys, along with severe oligohydramnios. The underlying pathology is that of dilated tubules, and these appear echogenic (brighter than the liver) in scans. The fetal bladder is either small or is not visualised. It is important to emphasise that infantile polycystic kidney disease might not develop until late in the second trimester in fetuses with enlarged, echogenic kidneys [21]. Adult-type polycystic kidney disease Potter type III is also known as adult-type polycystic kidney disease with autosomal dominant inheritance. It is the most common hereditary renal cystic disease in infancy and adulthood. The onset

Fig. 3. Infantile polycystic kidney disease (prenatal type) at 20-week scan.

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of renal cysts varies from fetal to neonatal period, but renal failure usually develops in adulthood. There is a 50% chance of recurrence in consequent pregnancies [22]. In 90% of cases, the abnormality is in gene 6p, and, in 10% of cases, the abnormal gene is on 4q. Multiple cysts of varying sizes are seen with cysts in the pancreas, liver, spleen, and central nervous system. In ultrasound scans, bilateral symmetrically enlarged kidneys can be seen, and the small cysts appear echogenic [23]. Amniotic fluid amount is normal, and the bladder appears normal compared with the infantile type. Prenatal diagnosis can be offered with chorionic villous sampling, and a family history is essential to diagnose and differentiate from infantile polycystic kidney disease. Therefore, the finding of renal cysts in the fetus warrants ultrasound scanning of parents’ kidneys. In infants with cystic kidneys and no family history, tuberous sclerosis should be actively excluded. Obstructive uropathy Upper urinary tract dilatation Upper urinary tract dilatation is one of the most common abnormalities diagnosed prenatally by ultrasound scanning. It is commonly caused by transient urine flow impairment at the level of the pelvi-ureteric junction (PUJ) and vesico-ureteric junction, which improves with time in most cases [24]. Prognosis of the condition is mainly determined during the first 18 months of life. Renal tract dilatation can be detected prenatally by ultrasonography between 18 and 20 weeks. Normal renal pelvis is readily visualised when the antero-posterior diameter of the renal pelvis is greater than 2 mm (Fig. 1). Renal pelvis dilatation (RPD) is significant when it is over 6 mm before 24 weeks and over 10 mm after 30 weeks [25] (Fig. 4). It is seen in 50% of prenatally detected renal anomalies [26]. It can be either unilateral or bilateral, with a male to female ratio of 2:1 [27]. Although inadequate research on postnatal management has been published, RPD of 6 mm or greater in the second trimester and 10 mm or greater in the third trimester warrants postnatal investigation. Progressive reduction in liquor volume with prenatally detected renal dilatation is significant, as it would indicate poor renal prognosis. Isolated mild RPD (7–10 mm) does not pose additional risk of underlying chromosomal aneuploidy in the fetus. In the presence of other anomalies or positive screening for Down’s syndrome, karyotyping of the fetus is indicated [28–31]. Pelvi-ureteric junction anomalies are the most common, accounting for 35% of prenatal urological problems [32]. Incidence of PUJ is 1 in 2000, with male predominance; in most (90%) cases, obstruction is unilateral [33]. Prenatally RPD is seen with ureteric dilatation and a normal bladder. As the obstruction continues, the renal cortex becomes thinner, with increased cortical echogenicity, presence of cortical cysts (Fig. 5), or both. Amniotic fluid volume is usually normal when the anomaly is unilateral, but could cause oligohydramnios in the third trimester in bilateral severe disease. Serial scans are indicated antenatally to prognosticate the condition and to guide postnatal investigations [34].

Fig. 4. (A) Dilated fetal renal pelvises transverse section; (B) and coronal section.

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Severe PUJ anomalies can be managed prenatally by pelvi-amniotic shunting for urinary diversion, but this procedure is carried out rarely. In the case of bilateral or early onset disease, the prognosis is poor, and sometimes termination of the pregnancy could also be considered. Detailed examination of the rest of the urinary tract is essential, as 25% of cases are associated with other urological abnormalities, including renal agenesis, multicystic renal dysplasia, vesico-ureteric reflux (VUR), partial or complete ureteric duplication, and horseshoe kidney [35]. Moreover, nearly 12% of cases have other extra-renal abnormalities, such as anorectal anomalies, congenital heart disease, VATER syndrome, and oesophageal atresia, but no particular pattern exists unless associated with chromosomal abnormality [36]. Vesico-ureteric junction anomalies could be broadly divided in to non-functioning mega ureter and VUR. Primary non-functioning mega ureter (ureter >10 mm diameter) accounts for 10% of prenatal upper renal tract dilatation, with an incidence of 1 in 6500 [37]. Male-to-female ratio is 2:1, and 25% cases are bilateral [38]. Prenatal ultrasound shows a dilated ureter communicating with the dilated renal pelvis, with normally appearing bladder and liquor volume. The main differential diagnosis is VUR and obstruction caused by ureterocele or ectopic implantation of the ureter. A defective vesico-ureteric junction could lead to permanent or intermittent retrograde flow of urine from the bladder into the upper urinary tract and cause VUR. Abnormal anatomy at the vesicoureteric junction (primary VUR) and dysfunction of the lower urinary tract (secondary VUR) are known causes of VUR [39]. Postnatally, infants with VUR are at increased risk of upper urinary tract infections. Prenatally, 80% of diagnosed cases are males [40–43], and postnatally VUR is five times more common among females [44]. Lower urinary tract dilatation and abnormalities of the fetal bladder Lower urinary tract obstruction (LUTO) carries a high morbidity and mortality rate mainly caused by pulmonary hypoplasia secondary to oligohydramnios [45]. It affects 2.2 per 10000 births, out of which 64% are caused by posterior urethral valve (PUV), 39% for urethral atresia, 4% each for prune belly syndrome, and unidentified causes [46]. Males are affected more commonly and, if females are affected, a more complex pathology should be suspected, such as cloacal plate abnormalities or megacystis microcolon intestinal hypoperistalsis syndrome. Prenatal ultrasound scanning is accurate at diagnosing lower urinary tract obstruction (LUTO), with 95% sensitivity and 80% specificity [47]. The earliest sign of LUTO is distension of the fetal bladder (megacystis), which could be diagnosed as early as 11 weeks. Megacystis in the first trimester of gestation occurs in 1 in 1800 pregnancies, and most f these resolve spontaneously [48] (Fig. 6). Although bladder diameter increases with gestational age, bladder diameter is normally less than 10% of the crown–rump length. Longitudinal bladder diameter is less than 6 mm at 10–14 weeks [49]. Bladder diameters greater than 17 mm in the first trimester is most likely caused by obstructive factors, and experience progressive obstruction, whereas most fetuses with diameters of 8–12 mm would be resolved by 20 weeks. There is a 25% risk of an aneuploidy (trisomy 13 and 18) and associated malformations in 33% of fetuses [50]. In the second

Fig. 5. Severe upper urinary tract obstruction with thinner renal cortex with increased cortical echogenicity at 28 weeks.

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trimester, megacystis has been defined as an abnormally large appearing bladder, with or without the failure of the bladder to empty over 45 mins [51]. Posterior urethral valve is a developmental disorder that occurs in 1 out of 3000 live births. It could be diagnosed prenatally by ultrasound, with the presence of bilateral hydroureteronephrosis, megacystis, dilated posterior urethra, and a thickened bladder wall in a males (Fig. 7). In 25% of fetuses with megacystis, PUV is the likely reason for megacystis [52]. Thick bladder walls and a dilated posterior urethra (keyhole sign) are suggestive of PUV, although bladder walls may not thicken until later in pregnancy [51]. The main differential diagnosis of PUV is prune belly syndrome, which is characterised by abnormal abdominal muscles, bilateral cryptorchidism, and dilated ureters. Prenatal ultrasound findings of prune belly syndrome include renal dysplasia (50% of cases), hydroureteronephrosis, enlarged abdomen, and a patent urachus (up to 30%) [53]. Urethral atresia should be suspected in cases of severe megacystis found in the first trimester. It is appetent that the accurate prenatal diagnosis of cloacal malformation remains a challenge. Most published data are case reports in isolated studies indicating that the diagnoses was limited to the more complex type of cloacal malformations [54]. Fetal magnetic resonance imaging is often carried out in these complex cases [55]. Intrauterine therapeutic interventions In order to prevent potential complications of LUTO, intrauterine fetal therapeutic interventions have been proposed. The rationale for these interventions is to relieve the lower urinary tract obstruction, and thereby prevent renal damage and to minimise the risk of pulmonary hypoplasia. It is important to evaluate the fetal status and counsel the mother appropriately before the procedure, as the probability of survival with intact renal function is low with or without the intervention [56]. Two different therapeutic options are available, with specific technical approaches described for each. Little evidence has been published on the effectiveness of fetal cystoscopy as a diagnostic and therapeutic intervention for LUTO. Fetal cystoscopy could only be considered in a research setting, and further evidence is required to assess its effect on perinatal survival and long-term renal and bladder function for survivors [57]. Vesico-amniotic shunting is a relatively easy procedure, in which the fetus and fetal bladder are visualised continuously by real-time two-dimensional ultrasound while a vesicoamniotic pigtail catheter is inserted percutaneously through an introducer, and the shunt placed optimally (with the distal end in the fetal bladder and the proximal end in the amniotic cavity). Fetal viability should be confirmed immediately and at several hours after the procedure. Recently published randomisedcontrolled trials of percutaneous vesicoamniotic shunting compared with conservative management for fetal lower urinary tract obstruction were defaulted early owing to poor recruitment [56]. Freedman et al. [58] reported that, among children who survived after antenatal intervention for obstructive uropathies beyond 2 years, 36% had renal failure and had successful transplantation, 21% have renal

Fig. 6. Megacystis in the first trimester.

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Fig. 7. Dilated posterior urethra and megacystis in posterior urethral valves.

insufficiency, and 43% have normal renal function. Moreover, 50% of them had acceptable continent, and most of the remaining children had not begun (36%) and 14% were incontinent. Therefore, babies that survive, with or without prenatal intervention, have a significant risk of renal impairment, often necessitating renal dialysis or transplantation in childhood [57]. Genetic disorders and prenatally detected renal anomalies Many genetic disorders are linked with renal tract anomalies. Once a renal anomaly is detected prenatally, it is important to establish whether it is a part of a genetic syndrome. To establish a proper diagnosis, it is essential to have an overall knowledge about various syndromes associated with renal anomalies. Some of the common genetic disorders associated with renal malformations are presented in Tables 1 and 2. Conclusions The fetal renal system is routinely assessed mid-trimester by ultrasound. Upper urinary tract dilatation is the most common renal anomaly detected prenatally, and both vesicoureteral reflux after vesico-ureteric junction abnormality and pelvi-ureteric junction obstructive lesions should be considered. Renal parenchymal disease could be recognised in the fetus by visualising cystic changes in the kidneys or by appearance of abnormal echogenicity. Underlying abnormalities may be associated, and some may account for a genetic basis. The fetal bladder is a critical structure in lower urinary tract

Table 2 Renal manifestations associated with some chromosomal numerical aneuploidies. Chromosome anomaly

Renal pathology

Other major anomalies

Trisomy 1q

Dysplasia

Hydrocephaly; micrognathia; microphthalmia; imperforate anus. Absent gall bladder; talipes. Low set ears; talipes; rocker-bottom feet; clitoromegaly. Skeletal anomalies; cardiac defects. Growth retardation; microphthalmia; cardiac defects; vermis hypoplasia. Cleft lip/palate; brain anomalies; heart defects Growth retardation; characteristic face; heart defects; genital anomalies. Heart defects; duodenal atresia. Growth retardation; webbing neck; heart defects.

Mosaic Mosaic Mosaic Mosaic

trisomy trisomy trisomy trisomy

2 7 8 9

Trisomy 13 Trisomy 18 Trisomy 21 Turner syndrome XXX

Cysts Agenesis Agenesis, cysts Enlarged cysts Hypoplasia; cysts Horseshoe kidney; obstructive uropathy Tubular dysgenesis Horseshoe kidney; hypoplasia; cyst; obstructive uropathy Agenesis; hypoplasia

Mullerian abnormalities.

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to evaluate because both abnormal bladder size and absent bladder filling carry a poor prognosis. With the advent of high-resolution ultrasound equipment, imaging of fetal renal system during the first trimester is possible. Presence of megacystis at 11–14 weeks increases the risk of underlying chromosomal aneuploidy.

Practice points  Finding megacystis during the first trimester should be incorporated into the risk assessment of aneuploidy screening.  Fetal renal pelvis antero-posterior diameter 6 mm or over at 24 weeks and 10 mm or over at 30 weeks should be considered abnormal.  In the case of mild renal pelvic dilatation, follow-up scanning is indicated, and aneuploidy screening should be considered with the presence of other anomalies.  Presence of unilateral or bilateral renal agenesis and dysplastic kidneys could be a part of a genetic disorder.  Cystic kidney diseases may not be visible ultrasonically at 20 weeks; therefore, repeat scan may be indicated around 28–30 weeks in high-risk groups.  Early onset severe lower urinary tract obstruction carries a poor prognosis, and an option of termination of pregnancy should be discussed with the parents.  Intrauterine therapeutic interventions, such as vesico-amniotic shunts, could be considered in research set-up.

Research agenda  To determine optimum method and frequency of fetal monitoring in the presence of a renal tract anomaly.  To determine optimum timing of delivery in the presence a renal tract anomaly.  To determine the outcome of megacystis detected in the first trimester.  To determine the timing of intrauterine interventions (shunts) to optimise postnatal outcome.

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Ultrasound diagnosis of fetal renal abnormalities.

Development of the urogenital system in humans is a complex process; consequently, renal anomalies are among the most common congenital anomalies. The...
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