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Autosomal Recessive Polycystic Kidney Disease

Definition

Autosomal recessive polycystic kidney disease (ARPKD) is a rare hereditary polycystic kidney disease and liver fibrosis with variable manifestations in newborns, children, and adolescents (Guay-Woodford et al., 2014).

Epidemiology

Incidence 1:40 000 to 1:20 000.

Etiology

Autosomal recessive inheritance. The disease-causing gene defect has been mapped to chromosome 6. The mutations affect the PKHD1 gene, which encodes the protein fibrocystin. Fibrocystin plays a role in tubulogenesis and in maintaining the luminal architecture of the collecting ducts and bile ducts.

Pathology of Autosomal Recessive Polycystic Kidney Disease

Kidney:

Bilaterally enlarged kidneys with a usually preserved reniform shape. Histopathologically, cystic or fusiform dilatations are found predominantly in the collecting ducts; macroscopically, minute microcysts often predominate initially, whereas larger, macroscopically visible cysts may increase later in the course of the disease.

Liver:

Congenital hepatic fibrosis and ductal plate malformations with variable intrahepatic bile duct dilatation are typical. Portal hypertension, splenomegaly, hypersplenism, cholangitis, and biliary complications may result clinically.

Signs and Symptoms

The earlier the onset of the disease, the more pronounced the kidney involvement and respiratory insufficiency and the worse the life expectancy.

Onset at birth:

Enlarged echogenic kidneys, oligohydramnios, pulmonary hypoplasia, and abdominal distension after birth due to the enlarged kidneys are typical findings. Severe neonatal presentations can lead to respiratory insufficiency, arterial hypertension, electrolyte disturbances, and early kidney failure.

Onset after the sixth month of life:

Possible manifestations include chronic kidney insufficiency, arterial hypertension, polyuria, polydipsia, failure to thrive, as well as signs of congenital hepatic fibrosis with portal hypertension, splenomegaly, thrombocytopenia, esophageal varices, or recurrent cholangitis.

Diagnosis of Autosomal Recessive Polycystic Kidney Disease

Family history:

The family history should specifically inquire about prenatal deaths and unexplained kidney insufficiency in childhood. An unremarkable pedigree over multiple generations does not exclude ARPKD because of its autosomal recessive inheritance pattern.

Laboratory tests:

Basic parameters include creatinine, electrolytes, acid-base status, urinalysis, complete blood count, liver function tests, and coagulation studies.

Genetic evaluation:

Detection of mutations in the PKHD1 gene.

Ultrasound:

Renal ultrasound shows enlarged, diffusely hyperechogenic kidneys; this may be detectable prenatally. Macroscopically visible cysts usually do not appear until later in the course of the disease. In addition, the liver, spleen, portal vein, and signs of portal hypertension should be assessed.

MRI with MR cholangiography:

MRI can provide a more detailed assessment of kidney size, microcysts and macrocysts, as well as the hepatic parenchyma. MR cholangiography is particularly helpful when biliary dilatation or cholangitis is suspected.

Intravenous urography:

Historic examination, replaced by modern cross-sectional imaging. Typical findings were enlarged kidneys; on delayed images, contrast medium was seen in a radial pattern in the dilated collecting ducts.

Liver biopsy:

Only in uncertain cases.

Treatment of Autosomal Recessive Polycystic Kidney Disease

• Treatment of respiratory insufficiency during the first days of life
• Symptomatic treatment of hypertension, heart failure, kidney failure, and liver failure
• Treatment of end-stage kidney disease with peritoneal dialysis or hemodialysis or kidney transplantation
• Treatment of portal hypertension and its complications
• Liver transplantation or combined liver-kidney transplantation may be required in cases of severe hepatic involvement or combined hepatorenal insufficiency

Prognosis

The prognosis depends on the severity of perinatal pulmonary involvement and on the extent of the renal and hepatobiliary manifestations. Neonatal mortality is increased in the presence of severe oligohydramnios and pulmonary hypoplasia. For children who survive the first year of life, 10-year survival is about 80%. Approximately half of the patients who survive the early high-risk phase require dialysis or kidney transplantation by young adulthood.

Genetic counseling:

Siblings of affected children have a 25% risk of being affected, a 50% probability of being heterozygous carriers, and a 25% probability of being genetically unaffected.

References

Avner, E. D. & Sweeney, W. E. Renal cystic disease: new insights for the clinician.
Pediatr Clin North Am, 2006, 53, 889-909, ix

Guay-Woodford LM, Bissler JJ, Braun MC, et al. Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr. 2014;165:611–617.

Burgmaier K, et al. Autosomal Recessive Polycystic Kidney Disease – PKHD1. GeneReviews. Update 2024.

  Deutsche Version: Autosomal rezessive polyzystische Nierenerkrankung (ARPKD)

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