Polycystic kidney disease (PKD) is an inherited disorder with diffuse involvement of both kidneys. Aside from the presence of the cysts, there is no evidence of renal dysplasia. Multiple renal cysts frequently coexist with lesions in other viscera, especially the liver (Kaplan et al., 1989a). A renal cyst is defined as an enclosed sac or nephron segment lined by epithelial cells dilated to more than 200 μm. A cystic kidney is a kidney with three or more cysts present. Cystic kidney disease is the illness caused by a cystic kidney (Kaplan et al., 1989a).

As early as 1902, it was known that the age distribution of cystic renal disease had two peaks: one close to birth and the other between 30 and 60 years of age (Kaplan et al., 1989b). In general, the use of the term polycystic kidney disease is restricted to single-gene disorders: autosomal dominant PKD (traditionally known as adult onset) and recessively inherited PKD (traditionally known as the infantile form). Since the 1970s, physicians have understood that the adult form can also present during infancy. In the recessive form of PKD, generalized dilatation of the collecting tubules exists, whereas in dominant PKD, cysts develop in localized segments of the kidney anywhere along the nephron (Kaplan et al., 1989a).

The dominantly inherited form of PKD (ADPKD) is a highly penetrant nephropathy with variable clinical expression that presents mainly during adulthood, but the disease can also occur at any other time during life. Autosomal dominant polycystic kidney disease is the most common lethal genetic disease inherited as a dominant Mendelian trait (Wilson et al., 2006). Mutations in the PKD1 on chromosome 16 and PKD2 on chromosome 4 are responsible for 85% and 15%, respectively, of cases of ADPKD (Harris, 1999). In ADPKD, progressive asymptomatic enlargement of both kidneys occurs with a gradual decline in renal function. Ultrasonography can detect renal cysts in 56% of affected patients during the first decade of life, 80% during the second decade of life, and almost 100% of individuals by the third decade of life (Michaud et al., 1994). The infantile presentation of the adult onset form of PKD was not appreciated until 1971 (Shokeir, 1978).

Bilateral PKD can be attributed to two genetically determined conditions. The so-called infantile form of PKD is inherited as an autosomal recessive condition. The cystic dilations are fusiform and arranged radially throughout the kidney. The cysts are due to dilations of the distal convoluted tubules and collecting ducts. Concomitant cystic hepatic involvement is observed. Among survivors, hepatic fibrosis, cirrhosis, and portal hypertension occur.

From the perspective of prenatal diagnosis and neonatal presentation, the adult form of PKD is much rarer. It usually presents during the fourth to fifth decade of life. The kidney contains multiple cysts, ranging in size from microscopic to gross, located in both the cortex and the medulla. The intervening areas of the kidney may be normal (Shokeir, 1978).

ADPKD is now considered a systemic disorder. The extrarenal manifestations include liver cysts, cysts of the pancreas, and intracranial aneurysms, which occur in 5% of patients and lead to subarachnoid hemorrhage. There is also an increased prevalence of cardiac valve defects, hernias, and colonic diverticulum (European Polycystic Kidney Disease Consortium, 1994).

The recessively inherited form of polycystic disease (ARPKD) manifests during the neonatal period with respiratory distress or during early infancy with renal insufficiency. There is a wide variation in clinical course (Wisser et al., 1995). The renal involvement in autosomal recessive polycystic kidney disease (ARPKD) is invariably bilateral and largely symmetrical. It is always associated with generalized portal and interstitial fibrosis of the liver (Romero et al., 1984; Zerres et al., 1988). In 1971, Blyth and Ockenden subdivided patients with ARPKD into four groups according to the proportion of dilated renal tubules present. The perinatol classification was associated with the onset of renal failure in utero or at birth and resulted in perinatol or neonatal death. These patients had at least 90% involvement of the renal tubules. The neonatal presentation resulted in a smaller kidney size and mild hepatic fibrosis, but these patients died within 1 year and had 60% of their kidneys affected. The infantile presentation resulted in clinical symptoms by the age of 3 to 6 months, moderate hepatic fibrosis, and hepatosplenomegaly with progressive chronic renal failure, and systemic and portal hypertension. These patients had 25% of their kidneys affected. The latest presentation was the juvenile onset, which occurred between 6 months and 1 year of age and had only 10% of the kidney affected (Blyth and Ockenden, 1971).

ADPKD is one of the most common hereditary disorders in humans. It is 10 times more common than sickle cell disease, 15 times more common than cystic fibrosis, and 20 times more common than Huntington disease (Gabow, 1993). The incidence of ADPKD is 1 in 1000 living individuals, with a penetrance rate of 100% (McHugo et al., 1988). Approximately half of the affected patients present during the third to fifth decade of life with hypertension or uremia. ADPKD has been noted to occur in 1 of 500 autopsies (Pretorius et al., 1987). Because of its effect on mortality, ARPKD is less common in the general population, but it is disproportionately increased in the prenatally diagnosed population. The incidence of ARPKD is 1 in 40,000 births (Zerres et al., 1988).

Malformations of the urinary tract are detected at a high rate because they are associated with two easily visualized sonographic markers: cystic accumulation of fluid and change in amniotic fluid volume.

Bronshtein et al. (1990) described transvaginal sonographic studies in 1940 in pregnant women at between 10 and 16 weeks of gestation. In the study population, 35 fetuses with renal anomalies were identified (1.8%), and among this group, 2 cases of ARPKD were diagnosed. These authors demonstrated that the fetal kidneys could be imaged as early as the 12th week of gestation, when they appear as hypoechogenic oval masses on both sides of the fetal spine. Indirect evidence of urine production can be inferred by observing emptying of the bladder as early as 18 weeks of gestation. In two cases, the study’s authors were able to identify fetal kidneys as early as 9 weeks of gestation. In this report, two types of cystic renal anomalies were described: microcystic, which was defined as the presence of multiple small cysts in the affected kidney, resulting in a spongiform enlarged kidney that comprised most of the fetal abdomen on the longitudinal and transverse scans; macrocystic, in which the sonographic appearance of the affected kidney resembled polycystic ovaries seen in adult women. In the two cases of ARPKD, the amount of amniotic fluid observed was normal. Zerres et al. (1988) described their observations in the prenatal sonographic diagnosis of ARPKD. They noted that increased echogenicity and renal enlargement were the characteristic findings of ARPKD. Oligohydramnios can be present, but it is not required for the diagnosis. These authors thought that the most useful parameter in the prenatal diagnosis of ARPKD in families known to be at risk were repeated sonographic measurements of fetal kidney length. They concluded that prenatal sonographic diagnosis was possible only in severe cases of ARPKD. Oligohydramnios presenting during the first or second trimester carried a very poor prognosis. In a third study, Romero et al. (1984) described their observations in 19 fetuses at risk for ARPKD because of a known family history. Ten (53%) of these fetuses were affected. A definitive antenatal diagnosis of ARPKD was made by the presence of oligohydramnios, an absent urinary bladder, and bilateral renal enlargement, as measured by the kidney circumference to abdominal circumference ratio. The ratio in affected fetuses was > 2 standard deviations (SD) above the mean. These authors described a typical hyperechogenic appearance of the kidneys in ARPKD. They had no false-positive diagnoses, but there was one false-negative diagnosis. In contrast, the unaffected neonates had normal bladders, normal amniotic fluid volume, and normal kidney texture. False-negative diagnosis has been reported in ARPKD. Luthy and Hirsch (1985) described a couple with two previously affected pregnancies with ARPKD. Ultrasound examination performed at 25 weeks of gestation in a subsequent pregnancy revealed oligohydramnios, increased renal parenchymal echogenicity, and a normal renal size and normal bladder. The pregnancy was terminated electively, and at autopsy, the kidneys were shown to be normal.

Okumura et al. reported that ARPKD can be associated with densely echogenic renal pyramids (Okumura et al., 2006). They found on histology that this was due to the ectatic tubules of the pyramids in ARPKD producing multiple reflection interfaces resulting in increased echogenicity. This is a pattern of increased echogenicity that can also be seen in medullary nephrocalcinosis. This appearance has also been observed in a neonate with ARPKD (Herman and Siegel, 1991).

The prenatal diagnosis of ADPKD was first reported by Zerres et al. in 1982, who described enlarged abnormally reflective kidneys with cysts (see Figure 79-1). In a subsequent study, McHugo et al. (1988) described the presence of enlarged fetal kidneys with accentuation of the corticomedullary differentiation but no cysts. These authors thought that this specific finding distinguished between the recessive and dominantly inherited forms of PKD. Of concern in ADPKD is the fact that the sonographic lesions are detected long before the appearance of symptoms. Very few data exist concerning the rate of progression of disease in ADPKD. One report described normalization of fetal renal size in an unaffected fetus (Jeffery et al., 1998). No ultrasonographic criteria exist for clinical staging of this disease except for the presence of oligohydramnios, which carries a poor prognosis (Michaud et al., 1994). One review of 83 reported cases of ADPKD presenting in utero showed a 67% incidence of hypertension in childhood and a 43% incidence of death in the first year of life (MacDermot et al., 1998).

In a study of prenatal diagnosis of ADPKD, Pretorius et al. (1987) described five cases ascertained at their center and combined their clinical information with eight cases reviewed in the medical literature. All 13 fetuses identified had 1 parent affected, but only 5 of the 13 affected parents were aware of their diagnosis prior to pregnancy. Eleven of the 13 affected fetuses with ADPKD had renal enlargement, 10 had increased echogenicity, and 9 had specific echogenicity of the renal parenchyma. Only 6 of 13 had cysts large enough to be detected by antenatal ultrasound examination.

Echogenic kidneys with normal amniotic fluid volume pose a distinct diagnostic challenge. As reported by Mashiach et al., this can be a normal variant, as was the case in one of their seven patients (Mashiach et al., 2005). However, six of the seven patients had significant renal parenchymal disease, four patients had ADPKD, and two patients had multifocal renal dysplasia.

Fetal MRI has been used more frequently to help delineate the etiology of enlarged kidneys because of the limitations of ultrasound examination in the setting of oligohydramnios. Liu et al., described the following MRI findings on single-shot fast spin echo (SSFSE) sequences in ARPKD: hypointensity of the lungs (because of decrease in airway fluid from oligohydramnios), oligohydramnios, symmetrical nephromegaly, and nonvisualization of fluid in the renal pelvis and bladder (Liu et al., 2006). Hawkins et al., found MRI helpful in diagnosing the underlying basis for severe renal anomalies (Hawkins et al., 2008). Similarly, Cassart et al., found MRI to be complementary to ultrasound examination, and in the case of ARPKD, found a hyperintense signal in the pyramids similar to the increased echogenicity observed by sonography by Okumura et al. (Cassart et al., 2004, Okumura et al., 2006).

When cysts are observed in the fetal kidney, it is important to determine whether they are present in only one kidney or in both. Bilateral presentation is more characteristic of ARPKD. Caution must be observed, however, as ADPKD can be difficult or impossible to prenatally distinguish sonographically from ARPKD (Pretorius et al., 1987). Furthermore, the differential diagnosis of diseases that causes echogenic kidneys in the fetus and newborn differs from that of older pediatric patients (Estroff et al., 1991). Renal cysts can be characteristically found as part of other single-gene disorders, including tuberous sclerosis (Blethyn et al., 1991). It is of interest that one of the genes for tuberous sclerosis maps very closely to one of the genes for ADPKD. Blethyn et al. (1991) described a fetus with a large echogenic kidney diagnosed at 28 weeks of gestation. This infant was later noted to have seizures at 5 weeks of postnatal age, and computed tomographic (CT) scan revealed the presence of cortical tubers. Renal lesions occur in 54% to 100% of patients with tuberous sclerosis. These consist of angiomyolipomas or renal cysts. Another condition that can present with increased echogenicity of the fetal kidneys and renal enlargement is Beckwith–Wiedemann syndrome. The other condition with bilateral renal enlargement, oligohydramnios, and increased echogenicity that presents prenatally is Meckel–Gruber syndrome (Wapner et al., 1981; Celentano et al., 2006). Sgro et al., have also reported the association of ARPKD and Caroli’s disease, which is a rare autosomal recessive condition (Sgro et al., 2004). This fetus was diagnosed at 33 weeks of gestation with dilated intrahepatic bile ducts and enlarged echogenic kidneys (see Figure 79-2). Other conditions that can present with renal cysts are listed in Table 79-1.