Autosomal recessive polycystic kidney disease (ARPKD) is the most common heritable cystic renal disease occurring in infancy and childhood. The clinical spectrum shows a wide variability, ranging from perinatal death to a milder progressive form, which may not be diagnosed until adolescence
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.
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.
Both sexes are affected equally.
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
Classification of ARPKD
In a landmark study, Blyth and Ockenden initially classified ARPKD into 4 groups: perinatal, neonatal, infantile, and juvenile.
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 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
Plain 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
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 . 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 . 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. In less severe cases, a sonolucent rim of cortical tissue may be present . 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