What are the extrarenal manifestations of autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD), and what screening and management strategies are recommended for these manifestations?

Extrarenal Manifestations of ARPKD and ADPKD

ADPKD Extrarenal Manifestations

The most critical extrarenal manifestations of ADPKD requiring systematic screening and management are hepatic cysts, intracranial aneurysms, cardiac valvular abnormalities, and hypertension, with liver involvement being the most common and hypertension being the earliest and most treatable manifestation affecting morbidity and mortality. 1, 2

Hepatic Manifestations

• Liver cysts are the most frequent extrarenal manifestation, present in >80% of ADPKD patients by age 30 years 3
• Polycystic liver disease can progress to massive hepatomegaly causing significant symptom burden and reduced quality of life 2
• Unlike ARPKD, ADPKD liver cysts do not involve congenital hepatic fibrosis or biliary dysgenesis 4
• Screening with imaging should be performed when patients develop symptoms of mass effect or when liver size impacts clinical management 2

Cardiovascular Manifestations

• Hypertension is the earliest and most common cardiovascular manifestation, affecting approximately 20% of children under 19 years and typically presenting at age 30-34 years in adults 1
• Elevated blood pressure is significantly associated with kidney volume and cyst score, and precedes loss of renal function 1
• Yearly blood pressure monitoring is mandatory for all ADPKD patients, including at-risk children who have not undergone diagnostic testing 1
• Ambulatory blood pressure monitoring (ABPM) is superior to clinic measurements and should be used routinely, as it detects masked hypertension in a substantial proportion of patients and isolated nocturnal hypertension in 16-18% of children 1
• Cardiac valvular abnormalities (particularly mitral valve prolapse and aortic regurgitation) occur frequently but rarely cause clinically significant problems 2, 5

Cerebrovascular Manifestations

• Intracranial aneurysms represent a critical vascular abnormality affecting life expectancy 2
• There remains ongoing debate regarding universal screening versus selective screening based on family history and risk factors 2, 5
• Screening should be considered in patients with family history of intracranial aneurysms or hemorrhage, high-risk occupations, or prior to major surgery 5

Other Systemic Manifestations

• Pancreatic cysts can occur but are generally asymptomatic 2
• Gastrointestinal manifestations include diverticular disease and hernias 5
• Bone disorders are an emerging area of clinical importance that can significantly influence disease course 2
• Male infertility may occur in some patients 5

ARPKD Extrarenal Manifestations

All patients with ARPKD develop congenital hepatic fibrosis (CHF) with intrahepatic biliary dysgenesis, making hepatobiliary disease the defining extrarenal manifestation that becomes increasingly important as patients survive beyond the neonatal period. 4, 6

Hepatobiliary Manifestations

• Congenital hepatic fibrosis affects 100% of ARPKD patients at the histological level, though clinical manifestations vary 6
• Intrahepatic biliary dysgenesis and non-obstructive dilation of intrahepatic bile ducts (Caroli's disease) occur in approximately 45% of infants 6
• Portal hypertension with variceal bleeding and cholangitis are life-threatening complications that occur more frequently in advanced liver disease 6
• As more ARPKD patients survive to adulthood, hepatic complications are becoming increasingly prevalent and may dominate the clinical picture 4, 7

Pulmonary Manifestations

• Oligohydramnios secondary to severe in utero renal dysfunction can lead to pulmonary hypoplasia 6
• This is a major cause of mortality in the perinatal period, with up to 30% of patients dying in this phase 6

Key Distinction from ADPKD

• ARPKD is confined to kidneys (polycystic kidneys) and liver (congenital hepatic fibrosis), whereas ADPKD is a systemic disease involving multiple organ systems 4
• ARPKD does not typically involve intracranial aneurysms, cardiac valvular disease, or pancreatic cysts 4, 6

Screening and Management Strategy

For ADPKD Patients

• Annual blood pressure monitoring with ABPM when available, particularly for children ≥120 cm height 1
• Screen for albuminuria annually in conjunction with blood pressure monitoring 1
• Hepatic imaging when symptomatic or when liver size impacts clinical decisions 2
• Consider intracranial aneurysm screening based on family history and individual risk factors 5
• Encourage low dietary salt intake as recommended for all children 1

For ARPKD Patients

• Systematic monitoring for portal hypertension complications including variceal bleeding 6
• Surveillance for cholangitis, which can be life-threatening 6
• Regular assessment of liver function and hepatic complications, which become more important with longer survival 4, 7
• Blood pressure monitoring, as hypertension affects approximately 45% of patients 6

Critical Pitfall

The most common error is failing to recognize that both ADPKD and ARPKD can present across all age groups—ADPKD can present in fetuses and infants, while ARPKD can present in adults 4, 7. This overlap necessitates consideration of both diagnoses regardless of age at presentation, particularly when genetic testing reveals unusual constellations such as biallelic mutations or contiguous gene deletion syndromes 1.