Renal cystic disease is a spectrum of genetic, developmental, and acquired abnormalities (Table 45-1). The clinical spectrum ranges from severe bilateral cystic renal dysplasia that results in death during the perinatal period to clinically inconsequential simple renal cysts. Genetic forms of cystic disease such as polycystic disease and renal cysts associated with syndromes are bilateral. Unilateral renal cysts occur with multicystic dysplastic kidney, developmental cysts, and cystic neoplasms.^1–3

The term renal dysplasia refers to embryonic maldevelopment of the kidney. This encompasses a varied group of malformations in which there is abnormal morphogenesis, differentiation, or structural organization of the kidney. Dysplastic kidneys may be large or small, functioning or nonfunctioning, and solid or cystic. Renal dysplasia can be diffuse or segmental. The presence of primitive structures is an important pathological feature of the various forms of renal dysplasia. Primitive ducts may be present in the medulla. Many dysplastic kidneys contain foci of cartilage. Other potential histological features include primitive glomeruli, ductules, and tubules.

A form of renal dysplasia can occur in association with severe lower urinary tract obstruction that occurs during fetal development or early in infancy. The pathophysiology of renal involvement in this situation is similar to that of multicystic dysplastic kidney; the severity of dysplasia roughly corresponds to the severity of obstruction. The timing of the obstruction during embryological development is also important. The most common cause of this type of renal dysplasia is posterior urethral valves.

In addition to collecting system dilation and parenchymal thinning, fetal or neonatal urinary tract obstruction can lead to the formation of multiple cysts. The cysts vary in size, but usually are less than 1 mm in diameter, that is, microcysts. Developing glomeruli in the nephrogenic zone are most susceptible to the effects of obstruction-related pressure elevation; therefore, the cysts are predominantly cortical.

Sonography of renal dysplasia due to severe lower urinary tract obstruction demonstrates marked hydronephrosis and parenchymal thinning. The dysplastic parenchyma is hyperechoic. The dilated pelvicaliceal system often has the appearance of multiple thin-walled cysts. Imaging in various planes allows documentation of communication between the structures. The most prominent fluid collection is located medially, representing the renal pelvis. Ipsilateral hydroureter is usually present. Rarely, the kidney has the appearance of a single large cyst, with little or no visible parenchyma. Even with severe parenchymal thinning and marked hydronephrosis, renal scintigraphy or MR urography confirms the presence of functional kidney tissue in these patients and allows differentiation from multicystic dysplastic kidney.

Multicystic dysplastic kidney (Potter type II renal cystic disease) is a developmental disorder in which multiple renal cysts replace functional renal parenchyma. This is among the most common renal malformations detected in the fetus and neonate. This lesion accounts for approximately 10% of fetal uropathies.⁴ The prevalence of multicystic dysplastic kidney in live newborns is 1 in 2400.⁵ This lesion is the second most common cause of a palpable abdominal mass in infants, after hydronephrosis.^6–8 There is a slight male predilection.^9,10 Contralateral urinary tract abnormalities are common in these patients.^11,12 There is an association with cystic dysplasia of the testis. Multicystic dysplastic kidney occurs with an increased incidence in patients with Turner syndrome, trisomy 21, Waardenburg syndrome, and chromosome 22 deletion.

Twenty percent of fetuses with multicystic dysplastic kidney have bilateral involvement. This lethal anomaly has a 2:1 female predominance. Many of these fetuses are stillborn. The prevalence of bilateral multicystic dysplastic kidney in live births is 1 in 10,000. Renal agenesis contralateral to a multicystic dysplastic kidney is an additional rare lethal association.

Over 50% of patients with multicystic dysplastic kidney have coexistent abnormalities of the urinary tract. The most common abnormality is contralateral vesicoureteral reflux, which occurs in 15% to 28% of these patients. A contralateral ureteropelvic junction obstruction is the next most frequent concomitant urological lesion. Megaureter is a rare associated anomaly. Any significant alteration in the contralateral kidney is particularly problematic in patients with multicystic dysplastic kidney, as the dysplastic kidney is nonfunctional. There is an overall reduction in the number of nephrons serving the patient, despite the presence of compensatory hypertrophy of the contralateral kidney. There is a substantial risk for long-term sequela such as proteinuria, hypertension, and chronic renal insufficiency (about half of patients), due to eventual decompensation of the remaining kidney. Careful imaging evaluation of the contralateral kidney in the child diagnosed with multicystic dysplastic kidney is essential to detect any potentially treatable lesions and to provide prognostic information.^13–18

A multicystic dysplastic kidney is composed of cysts and minimal solid tissue. The gross appearance can be likened to that of a cluster of grapes. The kidney lacks a reniform shape. There is usually no functional renal tissue. The number of cysts varies greatly between patients. The size of the kidney is also quite variable, ranging from an enlarged kidney with innumerable cysts to a kidney that is only a few centimeters in length. The histological features include cysts, metaplasia, and primitive glomeruli and tubules.

Multicystic dysplastic kidney results from abnormal differentiation of the metanephric tissue during embryonic development. The pathogenesis is likely related to complete obstruction or lack of development of the ureters during nephrogenesis (prior to 8 to 10 weeks gestational age). Abnormal interactions between the ureteric bud and embryonic renal mesenchyme are important factors.

Two types of multicystic dysplastic kidney are generally recognized. These are apparently determined by the level of collecting system atresia. The more common type is related to pelvoinfundibular atresia, which results in the presence of multiple noncommunicating cysts of varying sizes. There is no cortical or medullary parenchymal structure; the renal pelvis and infundibula are completely absent. Histological examination shows only a few scattered glomeruli and no normal collecting tubules.

The second type of multicystic dysplastic kidney is termed the hydronephrotic type. This is apparently due to embryonic ureteral atresia, without initial involvement of the pelvocaliceal system. In some patients, the pathogenesis involves an obstruction that is severe but incomplete. A prominent central cyst, which represents a partially developed renal pelvis, characterizes the hydronephrotic type of multicystic dysplastic kidney (Figure 45-1). In some instances, the central cyst communicates with adjacent cysts. Histological examination shows the presence of nephrons and primitive ducts.

There are rare instances of segmental multicystic dysplastic kidney that are due to atresia of a collecting system serving a duplex kidney. Either the upper or lower pole is dysplastic; there is a predilection for upper pole involvement. The adjacent portion of the duplicated kidney is normal or has an associated noncystic anomaly such as ureteropelvic junction (UPJ) obstruction or reflux. Spontaneous involution of the multicystic segment of the kidney is common.^19,20

Imaging of Multicystic Dysplastic Kidney

Multicystic dysplastic kidney can often be detected prenatally with sonography or MR. This is the most common cystic renal lesion of the fetus. The appearance is that of multiple renal cysts and little or no renal parenchyma. The cysts increase in size and number on serial examinations; the cysts may be quite small and difficult to detect early in pregnancy. Any solid tissue that is present usually has abnormally prominent echogenicity. Severe oligohydramnios develops during the second trimester in the presence of bilateral multicystic dysplastic kidney.

The sonographic features of multicystic dysplastic kidney in the newborn are similar to those of late prenatal evaluations. There may be multiple cysts of varying sizes or a few large dominant cysts. Cysts should be carefully examined to confirm absence of communication, and thereby exclude the diagnosis of hydronephrosis (Figure 45-2). In children with the hydronephrotic type of multicystic dysplastic kidney, there is a prominent cyst centrally at the expected location of the renal pelvis. Communication of adjacent cysts with this structure is an occasional finding (Figure 45-3). Sonography demonstrates only minimal solid tissue within a multicystic dysplastic kidney, predominantly consisting of the cyst walls. The solid tissue is relatively echogenic; no sonographically normal parenchyma is visible. Doppler examination shows high resistive indices and little or no perfusion.

Renal scintigraphy is an excellent confirmatory test for the diagnosis of multicystic dysplastic kidney when sonography is equivocal.²¹ The lesion has complete lack of activity with renal agents, whereas even a severely dilated and thinned hydronephrotic kidney will have some activity (Table 45-2). Nearly any renal imaging agent can be utilized in this situation, including dimercaptosuccinic acid (DMSA), diethylene triamine pentacetic acid (DTPA), mercaptoacetyltriglycine (MAG3), and glucoheptonate. Contrast-enhanced MR urography provides similar information and allows detailed examination of the contralateral kidney. Some investigators recommend a repeat ultrasound in 7 to 10 days when there is uncertainty in the differentiation between multicystic dysplastic kidney and hydronephrosis. This allows for greater urine production and increased distention of an obstructed collecting system, while the appearance of a multicystic dysplastic kidney should not change over this short time.²²

Careful imaging evaluation of the contralateral kidney is mandatory in all infants with multicystic dysplastic kidney, as this kidney is at risk for various lesions such as dysplasia, hydronephrosis, and reflux nephropathy. The contralateral kidney usually has manifestations of compensatory hypertrophy. Ureteropelvic junction obstruction is relatively common in these patients. Various, sometimes subtle, manifestations of parenchymal dysplasia can occur as well: abnormal corticomedullary differentiation, abnormalities of calyceal number or morphology, renal cysts, and a weak or heterogeneous nephrogram.

Many multicystic dysplastic kidneys undergo spontaneous involution. Nearly 20% of multicystic dysplastic kidneys are undetectable with sonography at 1 year of age, and approximately 60% are undetectable by 6 years of age. Therefore, conservative treatment is appropriate for most children with this lesion. Nephrectomy is reserved for those neonates with a very large lesion that is causing substantial mass effect and for older infants with a persistent mass.^23,24 Complications of multicystic dysplastic kidney are quite rare.²⁵ There are case reports of malignancy arising in residual dysplastic tissue in these patients, usually Wilms tumor or renal adenocarcinoma (in adults). However, this rare association is no longer considered a justification for surgical resection of a multicystic dysplastic kidney in childhood. Hypertension is a questionable long-term complication.^26,27

Autosomal recessive polycystic kidney disease (ARPKD) is an uncommon genetic disorder that affects the kidneys and liver. The hallmark pathological features consist of renal collecting tubule dilation, bile duct hyperplasia, and periportal fibrosis. The distribution and severity of these changes vary substantially between patients, resulting in a clinical spectrum that ranges from severe renal involvement with normal liver function to portal hypertension with minimal renal manifestations. ARPKD is genetically distinct from autosomal dominant polycystic kidney disease (ADPKD). ARPKD has historically been referred to by various other terms, including infantile polycystic kidney disease, Potter type I kidney disease, sponge kidney, and polycystic disease of the newborn.^28–30

ARPKD occurs in 1 to 2 per 10,000 livebirths. About half of these infants die within the first month of life, usually due to pulmonary complications. The overall prevalence of this disorder is approximately 1 in 40,000 individuals. The responsible gene is PKHD1 at chromosome locus 6p12.2. This gene encodes for a membrane-associated receptor-like protein called fibrocystin. There is marked variability in phenotypic expression of ARPKD, even in individual families. This clinical spectrum of the disease is categorized according to the age of onset of the clinical manifestations into perinatal, neonatal, infantile, and juvenile forms (Table 45-3).^31–33

Most patients with ARPKD present in the perinatal or neonatal periods. There frequently is a history of oligohydramnios during pregnancy, due to poor fetal renal function. Oligohydramnios and compression of the fetal thorax by massively enlarged kidneys can produce the manifestations of the Potter phenotype in the affected neonate, with distinctive Potter facies and pulmonary hypoplasia. The neonate suffers a variable degree of respiratory distress and is oliguric. Pneumothorax and pneumomediastinum are common. The abdomen is enlarged and there are bilateral flank masses due to nephromegaly. Pulmonary insufficiency is sometimes fatal in severely affected newborns.

Patients with ARPKD who present beyond infancy usually have disease that is clinically dominated by hepatic manifestations. This end of the clinical spectrum of ARPKD is sometimes termed congenital hepatic fibrosis. These patients have periportal fibrosis and portal hypertension, leading to splenomegaly and varices. The nephromegaly is less pronounced than in those patients who present as infants; overt clinical manifestations of renal involvement may be absent.

The enlarged kidneys of patients with ARPKD usually retain their uniform shapes. Pathological examination shows enlargement of collecting tubules in association with cellular hyperplasia. The “cysts” of ARPKD actually represent markedly dilated collecting ducts. The dilated tubules communicate with functioning nephrons and open into the papillae. Although larger cysts occur in some affected children, most are quite small, measuring 1 to 2 mm in diameter. Hyperplastic epithelium lines the dilated collecting tubules. The pelvocaliceal systems develop normally.

Hepatic pathology in children with ARPKD consists of proliferation, dilation, and branching of well-differentiated bile ducts and bile ductules in association with a variable degree of periportal fibrosis. Septal bile ducts as well as small- and medium-sized interlobular bile ducts are affected. The parenchymal cells are normal. In those children with the juvenile form of ARPKD, there is marked periportal fibrosis.

Patients with neonatal or infantile onset ARPKD usually have clinical manifestations of tubular dysfunction, with a deficient ability to concentrate urine. Systemic hypertension is common. Failure to thrive occurs in many of these children. In older children, hepatic involvement may be manifest by hepatosplenomegaly and variceal bleeding. In those children who survive their first month, the survival rate without end-stage renal disease is 86% at 1 year, 78% at 5 years, and 67% at 15 years. Hypertension develops in 39% of patients with ARPKD during the first year of life, in 54% by 5 years, and 60% by 15 years. About one-quarter of patients experience variceal bleeding due to portal hypertension; the mean age for this complication is 12.5 years. Some degree of congenital hepatic fibrosis is always present in ARPKD and is extremely rare in autosomal dominant disease.^34–37

Imaging of ARPKD

Manifestations of ARPKD are sometimes detectable with prenatal sonography. However, the findings are nonspecific, and a lack of visible fetal abnormalities with sonography does not exclude the diagnosis. The most common findings are enlarged echogenic kidneys in association with oligohydramnios. On MR, the fetus with ARPKD may have enlarged kidneys that produce relatively high signal intensity on T2-weighted images, due to the innumerable small cysts and prominent water content of the kidneys.

Abdominal radiographs of the neonate with severe manifestations of ARPKD show bilateral flank masses. The diaphragm is elevated and the thorax is small; the appearance of the abdomen can simulate that of massive ascites (Figure 45-4). Pneumothorax and pneumomediastinum are common, particularly after the institution of assisted ventilation. Infants who are asymptomatic often have nephromegaly that is less pronounced and may not be demonstrable on abdominal radiographs. Hepatosplenomegaly is often the predominant finding in patients with this form of the disease. Renal calcifications are common by middle-to-late childhood.

Sonography confirms that the flank masses represent markedly enlarged kidneys. The kidneys retain reniform shapes. Fetal lobulation may be evident. There is loss of sonographic corticomedullary differentiation. There is prominent echogenicity of the renal parenchyma due to the multiple acoustic interfaces created by the dilated collecting tubules and cysts (Figure 45-5). Occasionally, there is a peripheral cortical rim that is hypoechoic relative to the remainder of the kidney. Although not pathognomonic, this finding is suggestive of the diagnosis of ARPKD (Figure 45-6). Scattered small cysts, usually no more than a few millimeters in diameter, are frequently visible on images obtained with a high frequency transducer (Figure 45-7). The presence of larger cysts is uncommon in infants and children with ARPKD, but does not exclude the diagnosis (Figure 45-8).

Sonography of children with childhood onset of ARPKD shows nephromegaly of lesser severity than that of the neonatal onset variety. There is abnormal prominence of parenchymal echogenicity, particularly in the medulla. Corticomedullary differentiation is deficient. Occasionally, discrete small cysts are visible. Parenchymal calcifications can develop, particularly in older children. Other potential sonographic findings in these children include hepatosplenomegaly, irregular biliary tract dilation, prominent hepatic echogenicity, and portosystemic collateral vessels.

Although not commonly performed in current practice, excretory urography has a characteristic appearance in infants with ARPKD. There is abnormal delay in appearance of the nephrogram and abnormal persistence. The nephrogram frequently has a heterogeneous, striated appearance. Delayed radiographs show a “spoke wheel” pattern due to the accumulation of contrast within ectatic tubules and collecting ducts. The thin linear collections of contrast are arrayed in a radial pattern, extending from the cortex to the medulla. The spoke wheel pattern does not occur with ADPKD. In some infants with ARPKD, severe compromise of renal function results in lack of detectable nephrograms or collecting system opacification on excretory urography. Childhood-onset ARPKD is associated with a striated character of contrast accumulation within ectatic collecting ducts in the medullary portions of the kidneys. Excretion of contrast is relatively prompt.

Unenhanced CT of the infant with ARPKD shows bilateral nephromegaly. Because the proportion of fluid within the renal parenchyma is elevated by the dilated tubules, renal parenchymal attenuation is somewhat diminished and approaches that of water (Figure 45-9). Contrast-enhanced images show similar findings to those described above with excretory urography. Function is delayed and the parenchyma eventually develops a striated appearance due to the accumulation of contrast in the dilated tubules. CT examinations of patients with childhood-onset disease demonstrate nephromegaly of lesser severity than occurs with early onset varieties. Nephrocalcinosis is common. Contrast-enhanced images sometimes show striations within the medullary pyramids, but this finding is not present in all patients. Multiple discrete nonenhancing cysts can frequently be identified. Liver involvement in these older patients results in CT findings of hepatosplenomegaly, bile duct dilation, hepatic cysts, and portosystemic collaterals.³⁸

Although not commonly performed, the morbid anatomy of ARPKD can be evaluated with MR. In affected infants, MR shows massive nephromegaly. There is prominent parenchymal signal intensity on T2-weighted images due to the elevated water content of the kidneys. Radial striations corresponding to the dilated collecting tubules are sometimes visible. In older children, MR may show bile duct dilation as well as varices and portosystemic collateral vessels due to portal hypertension.

Differential Diagnosis of ARPKD

The diagnostic imaging findings in children with the perinatal, neonatal, and infantile forms of ARPKD are rarely pathognomonic. Depending on the specific findings for the individual patient and the clinical history, various conditions can be considered in the differential diagnosis. ADPKD is the most important differential diagnostic consideration in many of these children. Although clinical manifestations of ADPKD are rare in neonates, there are unusual instances in which the imaging findings are indistinguishable from those of ARPKD. The spoke wheel pattern on excretory urography and the peripheral hypoechoic cortical rim on sonography are useful features that, when present, are relatively specific for the diagnosis of ARPKD. The identification of renal cysts in affected family members strongly supports the diagnosis of ADPKD. Maternal oligohydramnios and perinatal renal insufficiency are generally not associated with the dominant form of the disease.

There is a rare form of transient neonatal nephromegaly that can clinically and radiographically mimic ARPKD in the newborn. The nephromegaly is apparently due to transient intratubular obstruction, possibly related to the accumulation of Tamm-Horsfall protein. Terms for this condition include Tamm-Horsfall proteinuria and tubular stasis nephropathy. There may be clinical evidence of bilateral flank masses. Excretory urography shows diminished renal function and persistent nephrograms. The pyramids have slightly increased attenuation on unenhanced CT. Sonography shows nephromegaly and prominent renal parenchymal echogenicity (Figure 45-10). Followup studies show rapid, complete resolution of these findings.³⁹

Bilateral renal vein thrombosis in the neonate can result in transient nephromegaly and diminished renal function. Sonography shows a heterogeneous pattern of the renal parenchyma, usually with overall increased echogenicity. Careful examination may demonstrate clot within the larger renal veins, but the absence of clot does not exclude the diagnosis. Correlation with the clinical history aids in establishing the correct diagnosis for these infants; common predisposing factors are dehydration and maternal diabetes.

The findings on renal imaging of patients with a late childhood onset of ARPKD sometimes mimic those of medullary sponge kidney. However, medullary sponge kidney is not accompanied by hepatic disease. Diseases with renal involvement that can also have hepatic manifestations include Meckel syndrome,⁴⁰ juvenile nephronophthisis,⁴¹ Ivemark syndrome,⁴² Jeune syndrome,⁴³ COACH syndrome (cerebellar vermis hypoplasia/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis),⁴⁴ and Bardet-Biedl syndrome.⁴⁵

ADPKD is a common heritable disorder that is characterized by the development of and progressive enlargement of multiple cysts within the renal cortex and medulla. These patients are also at risk for various extrarenal manifestations of the disease, including cysts of other abdominal organs, intracranial aneurysms, and cardiac valve abnormalities. This is the most common inherited kidney disease. ADPKD was previously termed “adult polycystic kidney disease,” reflecting the usual (but not universal) age at clinical presentation. This disorder is present in 1 in 500 to 1 in 1000 livebirths.⁴⁶ Approximately 600,000 individuals in the United States have autosomal dominant kidney disease. In adults, this is the fourth leading cause of end-stage renal disease.^47,48

ADPKD is a polygenic disorder. Approximately 85% to 90% of individuals with this disorder have the PKD₁ gene, which is located on chromosome 16p13.11-16pter; this is ADPKD type 1. A second responsible gene, termed PKD₂, is on chromosome 4q13-123, accounting for approximately 5% to 10% of cases—ADPKD type 2. Some families have no evidence of linkage to either of these genes. These genes encode polycystin-1 and polycystin-2. The PKD₂ mutation results in a milder phenotype and slower disease progression than the more common PKD₁ abnormality. In patients with the PKD₁ mutation, the age of onset of end-stage renal disease is earlier in individuals inheriting the disease from their mothers than that in those inheriting the disease from their fathers. Approximately 90% of ADPKD cases are due to inheritance of a mutant gene and 10% are due to sporadic mutations. However, a positive family history is lacking in approximately 40% of patients, apparently due to variations in the phenotypic expression of the disease. Because not all children with ADPKD are symptomatic or have diagnostic imaging abnormalities, DNA linkage analysis is the most sensitive diagnostic technique.^49–55

Unlike ARPKD, the cysts of ADPKD originate from a small number of nephrons and collecting ducts. The cysts originate as diverticula at sites of abnormal proliferation of renal tubular cells. The cysts initially communicate with the parent collecting tubules, but eventually lose this connection. Simple flattened or cuboidal epithelium lines the cysts. Transepithelial fluid secretion results in slowly progressive enlargement of the cyst despite lack of communication with the collecting tubule. The cysts can be located in the cortex or medulla, and most patients have cysts that are scattered in a haphazard pattern. The interstitium adjacent to each cyst is thickened, which may contribute to compromised renal function in these patients. Except in advanced disease, the intervening parenchyma between cysts is otherwise normal aside from compression. Large central cysts displace and distort the pelvicaliceal system. Dystrophic calcification within cyst walls is common.

Common clinical presentations of ADPKD include abdominal pain, hematuria, and manifestations of hypertension. Laboratory examination often demonstrates proteinuria and hyperlipidemia. There is a clinical spectrum of severity of ADPKD that is reflected in the age at presentation. Only 10% of individuals with ADPKD have overt clinical manifestations during the first decade of life. Clinical evidence of renal disease is quite rare in neonates and infants with this disorder. However, those neonates who are affected can suffer potentially fatal respiratory failure due to massively enlarged kidneys. In general, the presence or absence of symptoms and the age at clinical presentation correlate with the number and sizes of the renal cysts. Overall cyst volume and renal function are inversely related. Children with more than 10 cysts are likely to suffer flank or back pain, palpable kidneys, or hypertension.^56–59

Acute episodes of pain in patients with ADPKD are sometimes related to cyst hemorrhage. Hemorrhage can occur spontaneously or after minor trauma. Patients with polycystic kidney disease are at an elevated risk for renal injuries due to blunt trauma. There a propensity for urolithiasis, which can also cause acute pain. There is also an elevated susceptibility to renal infections. Most patients with ADPKD who have no major symptoms during childhood maintain adequate renal function as young adults. Approximately 50% of patients with ADPKD suffer no major complications of the disease over normal lifetimes. However, progression to end-stage kidney disease can occur in older adults with ADPKD. There does not appear to be an elevated risk for renal cell carcinoma.^60–63