eMedicine Specialties > Radiology > Genitourinary
Autosomal Recessive Polycystic Kidney Disease
Updated: Apr 24, 2008
Introduction
Background
Autosomal 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.
Autosomal recessive polycystic kidney disease (ARPKD). Excretory urogram of the same patient as in Image 1 demonstrates excretion into the bilaterally massively enlarged kidneys (arrows), with distorted pelvocalyceal systems and the vague suggestion of striated nephrograms.
Autosomal recessive polycystic kidney disease (ARPKD). Axial nonenhanced CT scan of a 1-day-old boy with ARPKD shows massively enlarged, hypoattenuating kidneys (K) that occupy most of the abdominal area.
Autosomal recessive polycystic kidney disease (ARPKD). Transaxial section through the same kidney (arrowheads) as in Image 9 demonstrates a very echogenic kidney with loss of the corticomedullary junction. Foci of intense echogenicity (arrows) may be due to the acoustic interfaces at the walls of tiny cysts or to focal renal calcification.
Related eMedicine topics:
Polycystic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease
Acquired Cystic Kidney Disease
Pathophysiology
ARPKD 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
Frequency
United States
Autosomal recessive polycystic kidney disease (ARPKD) has an incidence of 1 in 6,000 to 1 in 55,000 live births.
International
In Finland, the incidence is reported to be 1 in 1000.
Mortality/Morbidity
Autosomal recessive polycystic kidney disease (ARPKD) 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.
Race
No studies have shown a racial predominance.
Sex
Both sexes are affected equally.
Age
ARPKD may initially occur anytime between the perinatal period and 5 years of age, depending on classification.
Anatomy
Autosomal recessive polycystic kidney disease (ARPKD) 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.
Presentation
Typical features of ARPKD
Two constant features of the autosomal recessive polycystic kidney 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 Examination
Ultrasonography is the primary radiographic modality for the evaluation of autosomal recessive polycystic kidney disease (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 Techniques
Please see the sections concerning specific modalities below.
Differential Diagnoses
| Autosomal Dominant Polycystic Kidney
Disease | Medullary Sponge Kidney |
| Caroli Disease | Portal Hypertension |
| Cirrhosis | Tuberous Sclerosis |
| Esophageal Varices | Von Hippel-Lindau Syndrome |
Other Problems to Be Considered
Glomerulocystic disease
Bilateral renal vein thrombosis
Medullary cystic disease
Renal obstructive cystic disease
Diffuse cystic renal dysplasia
Congenital nephrotic syndrome
More on Autosomal Recessive Polycystic Kidney Disease |
 Overview: Autosomal Recessive Polycystic Kidney Disease |
| Imaging: Autosomal Recessive Polycystic Kidney Disease |
| Follow-up: Autosomal Recessive Polycystic Kidney Disease |
| Multimedia: Autosomal Recessive Polycystic Kidney Disease |
| References |
| Next Page » |
References
Al-Bhalal L, Akhtar M. Molecular basis of autosomal recessive polycystic kidney disease (ARPKD). Adv Anat Pathol. Jan 2008;15(1):54-8. [Medline].
Williams SS, Cobo-Stark P, James LR, Somlo S, Igarashi P. Kidney cysts, pancreatic cysts, and biliary disease in a mouse model of autosomal recessive polycystic kidney disease. Pediatr Nephrol. May 2008;23(5):733-41. [Medline].
Gigarel N, Frydman N, Burlet P, Kerbrat V, Tachdjian G, Fanchin R, et al. Preimplantation genetic diagnosis for autosomal recessive polycystic kidney disease. Reprod Biomed Online. Jan 2008;16(1):152-8. [Medline].
Gallagher AR, Esquivel EL, Briere TS, Tian X, Mitobe M, Menezes LF, et al. Biliary and pancreatic dysgenesis in mice harboring a mutation in Pkhd1. Am J Pathol. Feb 2008;172(2):417-29. [Medline].
Yang J, Zhang S, Zhou Q, Guo H, Zhang K, Zheng R, et al. PKHD1 gene silencing may cause cell abnormal proliferation through modulation of intracellular calcium in autosomal recessive polycystic kidney disease. J Biochem Mol Biol. Jul 31 2007;40(4):467-74. [Medline].
Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol. Sep 2002;13(9):2384-98. [Medline].
Lucaya J, Enriquez G, Nieto J, et al. Renal calcifications in patients with autosomal recessive polycystic kidney disease: prevalence and cause. AJR Am J Roentgenol. Feb 1993;160(2):359-62. [Medline].
Eggli KD. Autosomal recessive polycystic kidney disease. In: Pollack HM, McClennan BL, eds. Clinical Urography. 2nd ed. 2000: 1316-32.
Lonergan GJ, Rice RR, Suarez ES. Autosomal recessive polycystic kidney disease: radiologic-pathologiccorrelation. Radiographics. May-Jun 2000;20(3):837-55. [Medline].
Zerres K, Hansmann M, Mallmann R, Gembruch U. Autosomal recessive polycystic kidney disease. Problems of prenatal diagnosis. Prenat Diagn. Mar 1988;8(3):215-29. [Medline].
Jung G, Benz-Bohm G, Kugel H, et al. MR cholangiography in children with autosomal recessive polycystic kidneydisease. Pediatr Radiol. Jun 1999;29(6):463-6. [Medline].
Kern S, Zimmerhackl LB, Hildebrandt F, Uhl M. Rare-MR-urography--a new diagnostic method in autosomal recessive polycystic kidney disease. Acta Radiol. Sep 1999;40(5):543-4. [Medline].
Nasu K, Yoshimatsu J, Anai T, et al. Magnetic resonance imaging of fetal autosomal recessive polycystic kidney disease. J Obstet Gynaecol Res. Feb 1998;24(1):33-6. [Medline].
Nishi T. Magnetic resonance imaging of autosomal recessive polycystic kidneydisease in utero. J Obstet Gynaecol. Oct 1995;21(5):471-4. [Medline].
Sigmund G, Stover B, Zimmerhackl LB. Cystic diseases of the kidney in children: MRI including RARE-MR-urography. Eur Radiol. 1991;1:27.
Nishi T, Iwasaki M, Yamoto M, Nakano R. Prenatal diagnosis of autosomal recessive polycystic kidney disease by ultrasonography and magnetic resonance imaging. Acta Obstet Gynecol Scand. 1991;70(7-8):615-7. [Medline].
Avni FE, Guissard G, Hall M, et al. Hereditary polycystic kidney diseases in children: changing sonographic patterns through childhood. Pediatr Radiol. Mar 2002;32(3):169-74. [Medline].
Blickman JG, Bramson RT, Herrin JT. Autosomal recessive polycystic kidney disease: long-term sonographic findings in patients surviving the neonatal period. AJR Am J Roentgenol. May 1995;164(5):1247-50. [Medline].
Herman TE, Siegel MJ. Pyramidal hyperechogenicity in autosomal recessive polycystic kidney disease resembling medullary nephrocalcinosis. Pediatr Radiol. 1991;21(4):270-1. [Medline].
Nicolau C, Torra R, Badenas C, et al. Sonographic pattern of recessive polycystic kidney disease in youngadults. Differences from the dominant form. Nephrol Dial Transplant. Sep 2000;15(9):1373-8. [Medline].
Reuss A, Wladimiroff JW, Stewart PA, Niermeijer MF. Prenatal diagnosis by ultrasound in pregnancies at risk for autosomal recessive polycystic kidney disease. Ultrasound Med Biol. 1990;16(4):355-9. [Medline].
Slovis TL, Bernstein J, Gruskin A. Hyperechoic kidneys in the newborn and young infant. Pediatr Nephrol. Jun 1993;7(3):294-302. [Medline].
Stein-Wexler R, Jain K. Sonography of macrocysts in infantile polycystic kidney disease. J Ultrasound Med. Jan 2003;22(1):105-7. [Medline].
Zagar I, Anderson PJ, Gordon I. The value of radionuclide studies in children with autosomal recessive polycystic kidney disease. Clin Nucl Med. May 2002;27(5):339-44. [Medline].
Wisser J, Hebisch G, Froster U, et al. Prenatal sonographic diagnosis of autosomal recessive polycystic kidney disease (ARPKD) during the early second trimester. Prenat Diagn. Sep 1995;15(9):868-71. [Medline].
Tracey KP, Jen H, Metcalfe JB, McEwan AJ. Autosomal recessive (infantile) polycystic kidney disease demonstrated byTc-99m DMSA renal imaging. Clin Nucl Med. Nov 1991;16(11):833-5. [Medline].
Waters K, Howman-Giles R, Rossleigh M, et al. Intrahepatic bile duct dilatation and cholestasis in autosomal recessive polycystic kidney disease. Demonstration with hepatobiliary scintigraphy. Clin Nucl Med. Oct 1995;20(10):892-5. [Medline].
Blyth H, Ockenden BG. Polycystic disease of kidney and liver presenting in childhood. J Med Genet. Sep 1971;8(3):257-84. [Medline].
Ockenden BG, Blyth H. Polycystic disease of the liver and kidneys in childhood. Arch Dis Child. Feb 1970;45(239):148. [Medline].
Blyth HM, Ockenden BG. A clinico-pathological and family study of polycystic disease of the kidneys and liver in children. J Clin Pathol. Jul 1969;22(4):508. [Medline].
Further Reading
Keywords
autosomal recessive polycystic kidney disease, 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
