You are in: eMedicine Specialties > Radiology > GENITOURINARY Autosomal Recessive Polycystic Kidney DiseaseArticle Last Updated: Apr 24, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Ben Y Young, MD, Clinical Assistant Instructor, Staff Physician, Department of Radiology, Stony Brook University Hospital Ben Y Young is a member of the following medical societies: American College of Radiology Coauthor(s): Electra Veson, MPH, Department of Radiology, State University of New York at Stony Brook School of Medicine; Steven Perlmutter, MD, FACR, Clinical Associate Professor, Radiology Residency Program Director, Radiology Medical Director, Department of Radiology, University Hospital at Stony Brook; Thomas H Smith, MD, Associate Professor, Departments of Radiology and Pediatrics, State University of New York at Stony Brook Editors: John L Haddad, MD, Clinical Associate Professor, Department of Radiology, Weill Medical College of Cornell University; Director of Body MRI, Department of Radiology, Methodist Hospital in Houston; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Joshua A Becker, MD, Professor, Department of Radiology, New York University School of Medicine; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Clinical Assistant Professor of Radiology, University of Washington Medical School Author and Editor Disclosure Synonyms and related keywords: ARPKD, PDK, infantile polycystic kidney disease, polycystic disease of the newborn, hamartomatous form of polycystic kidney disease, polycystic kidney disease, Potter type I, chromosome 6, PKHD1, perinatal ARPKD, neonatal ARPKD, infantile ARPKD, juvenile ARPKD INTRODUCTIONSection 2 of 12
  BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is the most common heritable cystic renal disease occurring in infancy and childhood. It is distinct from autosomal dominant polycystic kidney disease (ADPKD), which tends to occur in an older population. The clinical spectrum shows a wide variability, ranging from perinatal death to a milder progressive form, which may not be diagnosed until adolescence. PathophysiologyARPKD follows an autosomal recessive inheritance pattern, with siblings of either sex having a 25% chance of developing disease while the parents are unaffected. The disease has variable expression, such that siblings may manifest different degrees of disease. Despite the clinical variability of ARPKD, it appears that a single unidentified gene is responsible for all forms of the disease. Linkage studies have localized an area on chromosome 6 (PKHD1) as the genetic locus. The frequency of the heterozygous state is estimated to be one in 70. The PKHD1 gene is expressed at high levels in the fetal and adult kidney and at lower levels in the liver, which corresponds to the principle sites of disease.1, 2, 3, 4, 5 ARPKD is characterized by pathologic changes in the kidney and/or liver. In the kidney, epithelial hyperplasia occurs along the collecting duct of the nephron. The hyperplastic cells undergo a functional change from being resorptive to becoming secretory. The fluid secreted from these abnormal cells is rich in epithelial growth factors, which further stimulate epithelial proliferation. The combination of epithelial hyperplasia and fluid secretion results in significant ductal ectasia. Approximately 10-90% of the ducts may be affected, resulting in a wide variability of renal dysfunction. Depending on the number of ducts involved, the kidneys may be massively enlarged. Examination of the kidney reveals multiple small subcapsular cystic spaces that correspond histologically with radially oriented, ectatic collecting ducts. Liver disease is present in every patient with ARPKD, with the manifestations varying according to the patient's age at presentation. The chief pathologic hallmarks of liver disease are periportal fibrosis and biliary duct ectasia. Significant liver involvement is referred to as congenital hepatic fibrosis. Although the mechanism is not clearly defined, the most common clinical manifestation of congenital hepatic fibrosis is portal hypertension.6, 7 FrequencyUnited StatesARPKD has an incidence of 1 in 6,000 to 1 in 55,000 live births. InternationalIn Finland, the incidence is reported to be 1 in 1000. Mortality/MorbidityARPKD accounts for 1.5% of children in renal replacement therapy before the age of 15 years and 0.6% of patients treated because of end-stage real failure before the age of 20 years. For additional information, see Anatomy and Clinical Details below. RaceNo studies have shown a racial predominance. SexBoth sexes are affected equally. AgeARPKD may initially occur anytime between the perinatal period and 5 years of age, depending on classification. AnatomyARPKD results in bilaterally generally symmetrically enlarged kidneys that maintain their reniform shape. Beneath the capsule are scattered opalescent cysts from dilated collecting ducts, usually 1-2 mm in diameter but sometimes larger. On sections, the renal parenchyma resembles a sponge with ectatic, nonobstructed, radially oriented collecting tubules that have areas of hyperplastic cuboidal or low columnar lining epithelium. Interstitial fibrosis develops, but the glomeruli remain normal. ARPKD results in dilated bile ducts with protrusions from the walls and bridging tissue between the duct walls. There are often increased numbers of ducts. There is congenital hepatic fibrosis with increased connective tissue in the enlarged portal tracts. Generally, there is a reciprocal relationship between the degree of renal and hepatic involvement in individual patients. Those with more severe renal involvement have less severe hepatic disease. Clinical DetailsTypical features of ARPKD Two constant features of the disease are kidney and liver involvement of variable severity. Generally, renal and hepatic disease manifest opposite degrees of severity. Patients who develop severe kidney disease early in life tend to succumb to renal failure before significant hepatic disease can develop. On the other hand, patients with a milder form of kidney disease tend to develop severe hepatic complications later in life. The main characteristic of kidney involvement is dilatation of the collecting system, which results in multiple cysts and manifests as progressive renal failure. Disease in the liver is typically diffuse, presenting as portal and interlobular fibrosis, dilatation and hyperplasia of bile ducts, or a combination of both. Liver disease ultimately results in portal hypertension.8, 9 Classification of ARPKD In a landmark study, Blyth and Ockenden initially classified ARPKD into 4 groups: perinatal, neonatal, infantile, and juvenile. The 4 categories are based on the individual's age and the onset of clinical manifestations; however, the disease is characterized by a spectrum of findings and is not easily classified into clearly defined subcategories.28, 29, 30 Category 1 is perinatal ARPKD. Patients with the perinatal form are born with a markedly enlarged abdomen due to nephromegaly, which may interfere with delivery. Approximately 90% of the collecting ducts are dilated, and there is minimal liver involvement. Severe renal impairment in utero leads to oligohydramnios and subsequent pulmonary hypoplasia. Other clinical findings may include sequelae of oligohydramnios, such as Potter facies and clubfoot. Most infants do not survive beyond the first week of life. Unfortunately, such severity of disease is seen in approximately 75% of all cases of ARPKD. Category 2 is neonatal ARPKD. Patients with the neonatal form have palpable kidneys at birth. Approximately 60% of the kidney is affected, and there is mild liver disease. Pulmonary involvement is less of a factor in this form because renal impairment is often less severe in utero. Progressive renal failure is the dominant feature of this form, resulting in death within a few months. Category 3 is infantile ARPKD. The infantile form of the disease tends to manifest itself after a few months of life. Approximately 25% of renal collecting ducts are dilated, with moderate hepatic periportal fibrosis. Clinical presentation includes large kidneys and hepatosplenomegaly. Patients often develop chronic renal failure and/or portal and systemic hypertension. The disease often progresses to end-stage renal disease by adolescence; renal failure is the predominant cause of mortality. Category 4 is juvenile ARPKD. The hallmark of the juvenile form is pronounced hepatic involvement. Renal insufficiency is generally absent or mild, with less than 10% of the kidneys affected. The age at presentation varies from 6 months to 5 years. The presentation is characterized by variable renal enlargement and hepatosplenomegaly. Significant liver involvement results in portal hypertension. Morbidity and mortality are often secondary to the sequelae of portal hypertension, including variceal bleeding and thrombocytopenia or anemia secondary to hypersplenism. Mortality for this type is lowest among the 4 categories, with approximately 80% of patients surviving beyond the age of 15 years. Preferred ExaminationUltrasonography is the primary radiographic modality for the evaluation of ARPKD, especially during the perinatal and neonatal periods. Intravenous urography is less commonly used to evaluate the kidneys. In older children, CT and MRI are often used to evaluate liver disease.10 Limitations of TechniquesPlease see the sections concerning specific modalities below. DIFFERENTIALSSection 3 of 12
Autosomal Dominant Polycystic Kidney Disease Caroli Disease Cirrhosis Esophageal Varices Medullary Sponge Kidney Portal Hypertension Tuberous Sclerosis Von Hippel-Lindau Syndrome Other Problems to Be ConsideredGlomerulocystic disease
RADIOGRAPHSection 4 of 12
FindingsPlain radiography In the neonate, plain abdominal radiographs may demonstrate bilateral flank masses due to nephromegaly; these masses may cause the bowel to become displaced centrally (see Image 1). In severe cases, perinatal chest radiographs show Potter syndrome with hypoplastic thoraces and an elevated diaphragm. Occasionally, pneumothoraces or pneumomediastinum is observed. In the older child, hepatomegaly, splenomegaly, and nephromegaly are seen on plain abdominal radiographs. Intravenous urography In the neonate, intravenous urograms reveal decreased excretion of contrast material, nephromegaly, and characteristic striated nephrograms due to dilated collecting tubules (see Image 2). Contrast material may remain in the dilated tubules for days without visible excretion into the renal calyces. In more severe cases, renal excretion may be absent. Intravenous urography is rarely used in the very young infant. In the older child, intravenous urography demonstrates more rapid excretion and a striated nephrogram. On follow-up excretory urograms, kidneys that were initially enlarged are seen to be smaller or even of normal size. One should remember that intravenous contrast material is nephrotoxic in patients with renal failure. Esophagraphy Esophagraphic results can confirm the presence of varices in patients with portal hypertension. Degree of ConfidenceThe demonstration of organomegaly on plain images is a nonspecific finding. Plain radiographs are also insensitive for the detection of renal calcification in patients with ARPKD. False Positives/NegativesIn one study of patients with ARPKD, plain radiographs demonstrated only one seventh of the renal calcifications that were demonstrated on CT scans. Occasionally, renal function in neonates is so poor that their kidneys cannot be visualized with intravenous urography. CT SCANSection 5 of 12
FindingsIn the perinatal period, nonenhanced CT scans demonstrate nephromegaly with renal attenuation values approximating that of water. This feature is secondary to the water-containing, dilated, collecting tubules (see Image 3). After the administration of contrast material, striated nephrograms are observed; these are due to the stasis of contrast medium in dilated tubules with diminished excretion. In one study, 7 of 9 children aged 9-15 years had had CT scans that demonstrated renal calcifications. These calcifications were always bilateral and diffuse but tended to be more significant in ARPKD patients with moderate to severe renal failure. CT examination may also demonstrate hepatic duct ectasia, varices, and splenomegaly. One should remember that intravenous contrast material is nephrotoxic in patients with renal failure. Degree of ConfidenceCT is generally not required in the very young infant. False Positives/NegativesIntrahepatic bile ducts may appear either dilated or normal on CT examinations of patients with ARPKD. MRISection 6 of 12
FindingsMRI may be used to characterize the findings of ARPKD in utero, possibly with better detail than sonography. Fetal MRI demonstrates nephromegaly with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. This finding is attributed to the fluid-filled, ectatic collecting ducts. Renal MRIs of children with ARPKD may demonstrate nephromegaly with reniform-shaped kidneys and a homogeneous parenchymal signal pattern without pyelocaliectasis. The renal parenchyma has high signal intensity with T2-weighted sequences and usually has low signal intensity with T1-weighted sequences. In rapid acquisition with relaxation enhancement (RARE) magnetic resonance urography, hyperintense linear structures are seen radiating in the cortex and medulla. They represent dilated collecting ducts. Small subcapsular renal cysts may be seen. In a series of 8 children with ARPKD, MRIs failed to demonstrate hepatic fibrosis or bile duct dilatation.11, 12, 13, 14, 15, 16 Degree of ConfidenceAn unfavorable fetal position, a large maternal size, and oligohydramnios are some of the factors that can limit obstetric MRI. False Positives/NegativesMagnetic resonance cholangiography is more sensitive than sonography in the detection of biliary dilatation in children with ARPKD ULTRASOUNDSection 7 of 12
FindingsUltrasonography is often the first imaging modality used to diagnose cases of ARPKD. The diagnosis may be suspected because of enlarged, echogenic kidneys on an obstetric sonogram, on a newborn's sonogram obtained to evaluate abdominal masses or renal insufficiency, or on an older child's sonogram obtained to evaluate portal hypertension. The small size of a newborn or child facilitates the use of high-frequency ultrasound transducers that have outstanding resolution. The ability to perform imaging studies without the risk of sedation, intravenous contrast material, or ionizing radiation is an advantage of sonography. Images can be obtained in a number of planes to facilitate interpretation. In some circumstances, Doppler ultrasonography is used to evaluate blood flow. Prenatal sonography may demonstrate echogenic, enlarged kidneys, oligohydramnios, or an empty urinary bladder in severe cases of ARPKD; however, these findings are not demonstrable in all cases (see Images 4-5). Severely affected fetuses with oligohydramnios often have pulmonary hypoplasia, abnormal facies, and high mortality due to pulmonary insufficiency (Potter syndrome). In the neonate with ARPKD, sonograms usually show symmetric nephromegaly without contour-deforming masses (see Images 6-13). There may be fetal lobation, which is a normal finding. The kidneys are often diffusely echogenic. This has been attributed to reflection of the ultrasound waves from the many acoustic interfaces of dilated medullary collecting ducts, or perhaps to increased acoustic interfaces from interstitial edema. Frequently, there is loss of the differences in echogenicity that distinguishes the renal cortex from the renal medulla (see Images 6-10 and 13). In less severe cases, a sonolucent rim of cortical tissue may be present (see Image 11). This rim has variously been attributed to compressed cortical tissue without duct ectasia, to perirenal fluid, and to elongated thin wall cysts in the peripheral cortex. Discrete, small sonolucent cysts and, less frequently, larger cysts may occasionally be seen on sonograms of patients with ARPKD (see Image 8). These cysts are more likely to be demonstrated with modern high-resolution equipment (see Image 13). A rare but interesting case was reported in which the sonogram demonstrated focal sonolucent macrocysts that contained radiating septations. These corresponded pathologically to radially oriented, dilated collecting tubules. In premature infants with severe ARPKD, the increased echogenicity may be localized to the pyramids, mimicking medullary nephrocalcinosis (see Image 12). Because liver involvement tends to be less severe in newborns, the livers of newborns with ARPKD usually appear normal on ultrasonography; however, increased hepatic echogenicity or early bile duct ectasia on sonography has been reported. Long-term imaging demonstrates the emergence of hepatic fibrosis and portal hypertension and has been reported to show the development of splenomegaly, often with varices. In children and neonates, renal sonography may show increased echogenicity in the kidneys, particularly in the pyramids, loss of corticomedullary junction differentiation, mild to moderate nephromegaly, and (occasionally) dilated cystic-appearing collecting ducts. There are some published data regarding the patterns of serial renal growth and the changing patterns of renal echogenicity in children with ARPKD. One study of long-term survivors reported that renal size tends to peak at 1-2 years of age and then decreases until age 4-5 years, with the echogenicity returning to normal. Another group found little change in the nephromegaly over time and that diffuse hyperechoic foci correlated with the onset of renal failure. Renal calculi may be seen with sonography. Microcalcification in ARPKD is caused by the precipitation of calcium within dilated collecting ducts. This is attributed to decreased urinary citrate excretion and abnormally alkaline urine. Patients presenting in childhood often have portal hypertension. Long-term survivors with ARPKD develop portal hypertension secondary to hepatic fibrosis. The sonogram may show hepatosplenomegaly, echogenic livers, and ectatic bile ducts that contain nodular protrusions or bridge formation across the ductal lumen (see Images 14-15). Increased through-transmission of the ultrasound beam is seen beyond the dilated bile-filled ducts. Choledocholithiasis and complicating cholangitis may develop. Sonography of patients with portal hypertension may reveal collateral veins, and Doppler sonography demonstrates the velocity and direction of blood flow within the portal vein. Color-flow Doppler provides qualitative information, and duplex Doppler provides quantitative information about portal venous flow. Rarely, areas of intrahepatic duct ectasia with a central echogenic do may be seen in tpatients with ARPKD; such findings are characteristic of Caroli disease. Caroli disease has been associated with ARPKD.14, 17, 18, 19, 20, 21, 22, 23, 24, 25 Degree of ConfidenceUltrasonography is highly operator dependent, and its utility often depends on the skill of the person performing the study and not just the individual interpreting the final images. On renal sonography, small foci of intense echogenicity, with or without acoustic shadowing, have been attributed to either microcalcifications or reflections from the walls of multiple tiny cysts (see Image 10). Renal calcifications occur in ARPKD but are more frequently seen with CT than sonography. False Positives/NegativesIn utero, ARPKD is usually not diagnosed with obstetric sonography before the second half of pregnancy; however, ARPKD is uncommonly suspected on the basis of sonographic results during the early second trimester. ADPKD and glomerulocystic kidney disease can present in newborns with bilaterally enlarged echogenic kidneys that are indistinguishable from ARPKD. In these cases, the family history may suggest ARPKD. In approximately 10% of ADPKD cases, there is asymmetric renal involvement; is is very uncommon in ARPKD. Other conditions that have echogenic nephromegaly include bilateral renal vein thrombosis, congenital nephrotic syndrome, and diffuse cystic renal dysplasia that are seen in syndromes such as Meckel syndrome, Goldston syndrome, Zellweger syndrome, and Jeune syndrome. NUCLEAR MEDICINESection 8 of 12
FindingsIn the newborn with severe ARPKD involvement, renal scintigraphy shows enlarged reniform kidneys with poor function. In older children, hepatobiliary scintigraphy can demonstrate cholestasis and intrahepatic duct dilatation. Technetium-99m iminodiacetic acid (HIDA) hepatobiliary scintigraphy may demonstrate enlargement of the left lobe of the liver; delay in maximal hepatocyte uptake; delayed excretion of radionuclide into the biliary tree, which is often dilated; and delayed excretion into the bowel.24, 26, 27 Degree of Confidence99mTc DMSA renal scintigraphic findings are not specific and are variable. Reported patterns include both nonspecific discordant focal defects throughout the kidneys, particularly at the poles, and homogeneous renal uptake. In very young infants renal 99mTc mercaptoacetyltriglycine (MAG3) may show enlarged poorly functioning kidneys, even when the kidneys cannot be demonstrated by excretory urography. False Positives/NegativesIn a small minority of patients with ARPKD, results of renal or hepatobiliary nuclear medicine imaging studies are normal. ANGIOGRAPHYSection 9 of 12
FindingsAngiography is not usually required for patients with ARPKD. INTERVENTIONSection 10 of 12
Interventional radiology is not usually required in the management of ARPKD. Medical/Legal Pitfalls
MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
Autosomal Recessive Polycystic Kidney Disease excerpt Article Last Updated: Apr 24, 2008 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
