Unusual sonographic features of ARPKD

The classic sonographic appearance of the kidneys in fetuses with autosomal recessive polycystic kidney disease (ARPKD) has been well described. We report a case of enlarged kidneys with pyramidal hyperechogenicity quite similar to medullary nephrocalcinosis found in a fetus at 34 weeks' gestation. At 39 weeks, a female neonate was delivered and died after 22 h due to pulmonary insufficiency secondary to severe oligohydramnios. On pathological analysis, the gross and microscopic findings were typical of ARPKD with diffuse dilatation of tubules throughout. The fetal renal lobulation was prominent and on section, the pyramids were delineated within each lobule, accounting for the clear image of the pyramids observed on sonography. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal sonographic diagnosis of autosomal recessive polycystic kidney disease (arpkd) during the early second trimester

Autosomal recessive polycystic kidney disease (ARPKD) is a rare hereditary disease with a high neonatal mortality. Currently, prenatal diagnosis is possible only during the second half of pregnancy, when bilaterally enlarged, echogenic kidneys are visible by ultrasound. We describe a case in which a diagnosis of ARPKD was sought in the first half of pregnancy. High-resolution ultrasonography revealed echogenic, normal-sized kidneys at 15+4 weeks. Microsatellite DNA analysis of a chorionic villus sample, parental blood, and blood of an affected sibling showed that the fetus had the maternal haplotype and a recombination of the paternal haplotype. Thus, no distinction between homo- and heterozygosity for the ARPKD mutation in the fetus was possible. A further ultrasound examination at 19+4 weeks confirmed the previous results, indicating that the fetus was likely to be affected. After termination of the pregnancy, the diagnosis was confirmed on microscopic examination.     

Measurement of fetal urine production in mild infantile polycystic kidney disease—A case report

It is generally recognized that the sonographic findings of infantile polycystic kidney disease (IPKD) are bilaterally enlarged kidneys, oligohydramnios, an absent fetal bladder, and the typical kidney texture. Since there is a broad spectrum of renal compromise with IPKD, in utero diagnosis is thought to be limited to the severe forms. This paper reports a mild case of IPKD, where the in utero diagnosis was established by measuring fetal urine production and amniotic fluid volume serially during pregnancy, and by ultrasonographic examination of fetal kidneys.     

First and early second-trimester diagnosis of fetal urinary tract anomalies using transvaginal sonography

Urinary tract anomalies are common. Prenatal diagnosis is important and enables either special obstetric management or termination of pregnancy and probably in the future, intrauterine intervention. Transvaginal sonography (TVS) allows visualization of the normal and anomalous fetal urinary tract at an early stage. One thousand nine hundred and forty women were examined via TVS at an early stage of pregnancy between 10 and 16 weeks from the last menstrual period (LMP) and 35 anomalies (1·8 per cent) were clearly identified: 29 cases of low urinary tract obstruction, 2 cases of multicystic dysplastic kidney, 2 cases of polycystic kidney (infantile type), 1 case of double collecting system, and 1 case of horseshoe kidney. Potter syndrome could be ruled out in three patients who had delivered fetuses suffering from this anomaly in previous pregnancies. The concise and early identification of anomalies makes TVS an important aid in the hands of the obstetrician, ultrasonographer, and neonatologist.     

Unexpected ultrasonographic prenatal diagnosis of autosomal dominant polycystic kidney disease

The prenatal diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is now being reported with increasing frequency. We report three cases and review 12 cases of ADPKD diagnosed in the fetus by ultrasonographic findings. Increased echogenicity and renal enlargement are the main ultrasonographic signs of ADPKD. Renal cysts are uncommon. Diagnosis is easy in a family with a positive ADPKD history. Conversely, there may be no apparent family history, as in our three cases and three cases from the literature. We consider the problems of unexpected diagnosis, family investigation, and the prognosis of ADPKD in children with prenatally diagnosable forms.     

Severe bilateral renal disease: Correlation of antenatal and autopsy findings

We report 20 infants with severe bilateral renal disease examined by prenatal ultrasound and by autopsy. In 17, the prenatal and pathologic diagnoses correlated well. Although the prenatal and autopsy findings differed in the three remaining cases, the autopsy confirmed the presence of severe bilateral renal abnormalities. All 20 pregnancies were complicated by oligohydramnios, which was severe in 60 per cent. Most of these fetuses had malformation of other organ systems. This series supports the utility of prenatal ultrasound examinations, but emphasizes the need for postnatal evaluation of congenital renal disease including pathologic examination of tissue when possible for correct classification and genetic counselling.     

Prenatal diagnosis and obstetrical management of multicystic dysplastic kidney disease

Multicystic dysplastic kidney disease (MDKD) is one of the most common congenital renal anomalies. We report 16 consecutive cases of MDKD recognized in the antenatal period by sonography. Diagnosis is usually easy as MDKD has in the vast majority of cases a striking ultrasound appearance including enlargement of the kidney and multiple renal cysts. However, differentiation from obstructive uropathy may be difficult, and we made a total of five erroneous diagnoses. Unilateral MDKD has almost invariably a good prognosis. However, severe life-threatening associated anomalies were found in six cases. Therefore, a detailed survey of fetal anatomy and determination of karyotype are strongly recommended.     

The diagnostic potential of fetal renal biopsy

The feasibility of fetal renal biopsy has been investigated in order to assess the diagnostic value of the histological specimen. Two fetuses with a severe bilateral renal abnormality (multicystic dysplastic kidney, Meckel-Gruber syndrome with polycystic kidney) and one fetus with Down syndrome (no detectable structural anomaly) were sampled. Histological findings in the biopsy specimens of cases 1 and 2 were diagnostic of an early obstructive renal disease. In case 3 , the findings were consistent with normal development for gestational age of the kidney. Fetal renal biopsy is technically feasible; histological examination of the samples showed a good correlation with postnatal findings. Further studies of its diagnostic value are required.     

Short communications prenatal detection of the autosomal recessive type of polycystic kidney disease by trehalase assay in amniotic fluid

We report relatively high trehalase activity in amniotic fluid of a fetus affected with the autosomal recessive type of polycystic kidney disease (type II), suggesting that prenatal detection of this condition could be done on this basis in conjunction with ultrasonography.     

Potter's syndrome in the second trimester—prenatal screening and pathological findings in 60 cases of oligohydramnios sequence

Fifty-two second-trimester and eight third-trimester (>28/40) autopsies with clinical or pathological evidence of oligohydramnios sequence (“Potter's syndrome”) were reviewed. Twenty-eight cases had renal anomalies (71 per cent in terminations following prenatal ultrasound), 27 had no renal malformation (35 per cent with chorioamnionitis), and five had external assessments only. In 15 cases, the renal lesion was part of a multiple malformation syndrome. Seven cases had a lesion which either recurred in a sibling in the same family or was a recognized autosomal recessive syndrome. Three cases had an abnormal karyotype, two of which had renal anomalies. Maternal serum alpha-fetoprotein (AFP) did not discriminate between cases with renal malformations and those without. Pulmonary hypoplasia was commoner in third-trimester than in second-trimester cases. External appearance and absent umbilical artery were not reliable predictors of underlying internal anomalies. These findings reflect the shift from postnatal to prenatal diagnosis in modern practice. In this series, mainly second-trimester cases, 50 per cent of cases had no malformations, in a condition which is traditionally associated with renal disease. The high incidence of chorioamnionitis suggests that the mechanism of oligohydramnios is occult amniotic fluid leakage. Prenatal diagnosis of oligohydramnios in the second trimester is dependent on ultrasound scanning and a full post-mortem examination is necessary to identify any underlying fetal cause.     

Prenatal genetic considerations of congenital anomalies of the kidney and urinary tract (CAKUT)

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20% of all congenital malformations occurring in one in 500 live births. Worldwide, CAKUT are responsible for 40% to 50% of pediatric and 7% of adult end-stage renal disease. Pathogenic variants in genes causing CAKUT include monogenic diseases such as polycystic kidney disease and ciliopathies, as well as syndromes that include isolated kidney disease in conjunction with other abnormalities. Prenatal diagnosis most often occurs using ultrasonography; however, further genetic diagnosis may be made using a variety of testing strategies. Family history and pathologic examination can also provide information to improve the ability to make a prenatal diagnosis of CAKUT. Here, we provide a comprehensive overview of genetic considerations in the prenatal diagnosis of CAKUT disorders. Specifically, we discuss monogenic causes of CAKUT, associated ultrasound characteristics, and considerations for genetic diagnosis, antenatal care, and postnatal care.     

Clues and pitfalls in the early prenatal diagnosis of ‘late onset’ infantile polycystic kidney

Infantile polycystic kidney disease (IPKD) is an autosornal recesive inherited disorder, IPKD has been previously diagnosed by us as early as the 14th week of gestation. ‘Late onset’ (third trimester) IPKD has been previously described by several authors. We present here a case of intrauterine detection of ‘late onset’ IPKD, suggesting that elongated hyperechogenic kidneys (with normal transverse and anteroposterior diameters) should be considered as an early sign of ‘late onset’ presenting IPKD.     

Prenatal morphology in meckel's syndrome (with special reference to polycystic kidneys and double encephalocele)

Prenatal morphology of Meckel's syndrome was studied in five fetuses of different gestational age, that had been aborted because ultrasonography and elevated amniotic AFP-levels indicated neural tube defect. Histologically, the enlarged polycystic kidneys were completely alike with respect to the type of involvement and differed only in the severity of changes. They could be identified as type III cystic kidneys according to the classification of Potter. Proliferation of hepatic bile ducts and slight cystic dilatation of pancreatic ducts is already evident in the youngest fetus. Additional cyst formation in the epididymis was found in one of the cases. Occipital encephalocele, located within an apical occipital bone defect was always associated with a second mostly occult encephalocele protruding through a separate defect of the basal occipital squame and of the first and second vertebral arch. It is assumed that double encephalocele represents a constant finding in Meckel's syndrome, indicating a specific pattern within the disturbance of neural tube closure.     

Prenatal diagnosis of adult polycystic kidney disease with DNA markers on chromosome 16 and the genetic heterogeneity problem

A prenatal diagnosis of adult polycystic kidney disease by DNA testing is reported. Evidence showing a linkage between the disease and the 3′HVR and 24.1 restriction fragment length polymorphisms (RFLPs) on chromosome 16 was obtained in the proband's family by linkage analysis of data and homogeneity testing with Italian families of the linked type. Fetal genotype prediction based on both flanking markers was confirmed by histological and ultrastructural findings in fetal kidneys.     

Maternal serum alpha-fetoprotein levels and fetal outcome in early second-trimester oligohydramnios

Early second-trimester oligohydramnios was associated with normal maternal serum alpha-fetoprotein (MSAFP) levels in nine out of 26 cases (35 per cent). Congenital malformations of the fetal urinary tract resulting in fetal anuria were present in nine cases; in seven of them, normal MSAFP levels were measured. In contrast, normal MSAFP levels were established in only 2 out of the 17 cases without fetal malformations. These data suggest that fetal urine is the major source of elevated AFP in the maternal compartment in early second-trimester oligohydramnios. This is further supported by the lack of any relationship between concentrations of MSAFP non-reactive with Concanavalin A, originating mainly from the yolk sacderived amniotic fluid AFP pool, and the presence of fetal diuresis. Three out of 26 women had experienced early second-trimester oligohydramnios in a previous pregnancy, suggesting the existence of a recurrence risk for this condition.     

Oligohydramnios with amnio-chorionic separation at 15–16 weeks' gestation

Nine patients with oligohydramnios and amnio-chorionic separation were identified out of 7000 women who underwent a vaginal ultrasound examination at 15–16 weeks' gestation. Oligohydramnios was defined as a reduced amount of amniotic fluid, a distance of more than 1 cm between the chorion and amnion, and a good turgor of the amnion without floating membranes or intrauterine sheets. Fetal malformations were observed in all nine cases. In four of six fetuses where chromosomal analysis was available, an abnormal karyotype was found. It is concluded that oligohydramnios in the early second trimester is associated with fetal abnormality.     

Artificial instillation of amniotic fluid as a new technique for the diagnostic evaluation of cases of oligohydramnios

In cases of severe oligohydramnios, sonographic diagnosis is hampered by poor visibility and by increased fetal flexion. Therefore, 74 artificial instillations of amniotic fluid were performed in 50 pregnancies by sonographic guidance. Fetal diseases included Potter's syndrome, obstructive uropathy, cystic kidneys (20 cases); Meckel's syndrome, C. de Lange syndrome, cytomegaly fetopathy (1 case each); VATER association (2 cases); triploidy (5 cases); severe intrauterine growth retardation (8 cases); and premature rupture of membranes (12 cases). By improved sonographic visibility and the observation of fetal behaviour (drinking, filling of stomach and bladder, voiding of bladder after artificial instillation of amniotic fluid), the fetal anatomy could be studied more accurately, malformations could be identified or excluded, and bladder function could be examined. Thus, differentiation between fetuses without functioning kidneys and those with severe intrauterine growth retardation becomes possible. Further, re-aspiration on the day following instillation permitted determination of the karyotype. Finally, the artificial instillation of amniotic fluid is a hazardous intervention (rupture of membranes, labour) and should be reserved only for a small number of selected cases with diagnostically unclear oligohydramnios. For these cases, it seems to be the method of choice permitting a variety of diagnostic information to be obtained.     

A possible prenatal evaluation of renal function by amino acid analysis on fetal urine

Intrauterine treatment of 4 fetuses with urethral obstruction was attempted in the third trimester of pregnancy. The fetuses displayed varying sonographic findings including pyelectasis, caliectasis, hydroureter, bladder dilatation, ascites, hydrops, missing kidneys and oligohydramnios. Ultrasonically guided aspiration from the dilated structures was carried out to relieve pressure on the kidney parenchyme and to collect fluid samples for diagnostic purposes. Amino acid concentrations in the fetal urine showed a pattern similar to plasma in 2 fetuses, a pattern almost like urine in 1 fetus and an intermediate pattern in the 4th fetus. Only the fetus with normal amino acid concentrations in the urine survived: the other 3 died in uremia shortly after birth. In 3 cases cells from the aspirated urine were cultured and used for chromosome analysis. The cell cultures grew fast and karyotyping was possible within 1 week. In 2 fetuses an intrauterine catheter was inserted to drain the kidney permanently into the amniotic cavity. In the first case the catheter was displaced to the fetal abdomen after some days of successful drainage. In the second case the catheter tore the placenta, and the child had to be delivered immediately.     

Autosomal dominant polycystic kidney disease: Prenatal diagnosis by DNA analysis and sonography at 14 weeks

A pregnant woman affected with autosomal dominant polycystic kidney disease (ADPKD) had a history of an affected fetus, diagnosed by sonography at 29 weeks of pregnancy. The proband's father was also affected. DNA analysis performed on chorionic villi at 11 weeks during a second pregnancy predicted an affected fetus, and sonographic examination at 14 weeks confirmed the diagnosis.     

Anatomic correlates of ultrasonographic prenatal diagnosis

In utero sonographic diagnoses from forty-five malformed infants were correlated with their autopsy findings. Fifty-two malformations were diagnosed prenatally in 42 of the patients but 90 additional malformations were not. Nine sonographically diagnosed abnormalities were not confirmed at autopsy. Factors compromising sonographic diagnosis included: limited examinations, small fetal size, timing of examination, oligohydramnios, fetal position, nature of the malformation and unfamiliarity of the ultrasonographer with specific malformation syndromes. In vitro ultrasonography is an invaluable tool of diagnosing congenital malformations but has limitations.