You are here: Urology Textbook > Kidneys > Autosomal recessive polycystic kidney disease

Autosomal Recessive Polycystic Kidney Disease

Definition

Autosomal recessive polycystic kidney disease (ARPKD) is a polycystic kidney disease and liver fibrosis with variable manifestations in newborns, children and adolescents (Avner & Sweeney, 2006) (Hermanns et al., 2003).

Epidemiology

Incidence 1:20.000 to 1:40.000

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

Kidneys:

Bilaterally enlarged kidneys with preserved renal shape. Fusiform cystic dilatation of the collecting ducts (diameter 2 mm with progredient dilatation later in the course of the disease).

Liver:

Periportal fibrosis of the liver.

Signs and Symptoms

The symptoms and prognosis of autosomal recessive polycystic kidney disease differ with the age of the clinical manifestation.

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 6th 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.

Diagnostic Workup

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:

Mutations of the gene PKHD1.

Renal Ultrasound:

Renal ultrasound shows enlarged kidneys; this may be already detectable in fetal examinations. Hyperechogenic renal medulla, high-resolution ultrasound reveals microcysts. Larger cysts show up much later in the course of the disease.

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:

Late films show enlarged kidneys with contrast medium in the dilated collecting ducts. Intravenous urography is a historic examination, replaced by MRI.

Liver biopsy:

A liver biopsy is sometimes necessary in uncertain cases.

Treatment of Autosomal Recessive Polycystic Kidney Disease

• In the first days: treatment of respiratory insufficiency
• Symptomatic treatment of hypertension, kidney and liver insufficiency
• Treatment of end-stage renal disease with peritoneal dialysis or hemodialysis
• Treatment of portal hypertension and its complications
• In cases of severe hepatic involvement or combined hepatorenal insufficiency, liver transplantation or combined liver-kidney transplantation may be required.

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.

Siblings of affected children have, with autosomal recessive inheritance, 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)

Urology-Textbook.com – Choose the Ad-Free, Professional Resource

This website is designed for physicians and medical professionals. It presents diseases of the genital organs through detailed text and images. Some content may not be suitable for children or sensitive readers. Many illustrations are available exclusively to Steady members. Are you a physician and interested in supporting this project? Join Steady to unlock full access to all images and enjoy an ad-free experience. Try it free for 7 days—no obligation.

New release: The first edition of the Urology Textbook as an e-book—ideal for offline reading and quick reference. With over 1300 pages and hundreds of illustrations, it’s the perfect companion for residents and medical students. After your 7-day trial has ended, you will receive a download link for your exclusive e-book.