Participate in research.
Patients and families can play a direct role in advancing ARPKD/CHF research. Below are clinical studies actively recruiting participants.
Actively Recruiting
Natural History of Noncirrhotic Portal Hypertension
A study following the course of noncirrhotic portal hypertension, which can occur with Congenital Hepatic Fibrosis.
While almost all individuals with Autosomal Recessive Polycystic Kidney Disease (ARPKD) have underlying liver involvement (congenital hepatic fibrosis), noncirrhotic portal hypertension does not always develop, nor does it always present to a severe degree.
Liver involvement begins at birth on a microscopic level, but the progression toward clinically significant portal hypertension varies greatly from person to person.
Learn more about progression
- The liver connection: ductal plate malformation
- ARPKD is caused by mutations in the PKHD1 gene, which affect both the kidneys and the liver. In the liver, this leads to congenital hepatic fibrosis (CHF) — a condition where immature embryonic bile ducts persist and stimulate scar tissue in the portal areas. This scarring changes the architecture of the liver, creating resistance to blood flow and potentially leading to noncirrhotic portal hypertension.
- Variability in portal hypertension
- While the microscopic liver changes are universally present, clinical symptoms of portal hypertension — an enlarged spleen (splenomegaly), low platelets (hypersplenism), and esophageal varices — occur in only 36% to 70% of patients. For many, the scarring is mild enough that they never develop noticeable portal hypertension; for others, it appears later in childhood, adolescence, or even adulthood.
- Key differences from cirrhosis
- ARPKD-related portal hypertension is noncirrhotic: despite extensive scarring, the liver's functional tissue remains largely healthy. Because the liver's synthetic functions (filtering toxins, producing proteins) are preserved, patients typically do not experience liver failure as they would with traditional cirrhosis.
- Why does severity vary?
- Why some patients remain asymptomatic while others experience complications like gastrointestinal bleeding is not fully understood. Notably, there is no direct correlation between the severity of the kidney disease and the severity of the liver disease — some patients with relatively mild kidney function have more prominent liver and portal-hypertension phenotypes.
- Management
- Because the liver disease is noncirrhotic, management focuses on monitoring pressure indirectly (e.g., spleen size and platelet counts) rather than treating liver failure. When portal hypertension becomes symptomatic, it can be managed with medications, endoscopic procedures (such as banding varices), or occasionally shunts; liver transplants are rarely required.
Key references
- Kidney and liver transplantation in children with fibrocystic liver–kidney disease (US Scientific Registry of Transplant Recipients, 1990–2010)
- Occurrence of Portal Hypertension and Its Clinical Course in Patients With Molecularly Confirmed ARPKD
- Autosomal Recessive Polycystic Kidney Disease: A Hepatorenal Fibrocystic Disorder With Pleiotropic Effects
A Study to See If Tolvaptan Is Safe in Infants and Children with ARPKD
Evaluating the safety of tolvaptan in patients from 28 days to under 18 years old with Autosomal Recessive Polycystic Kidney Disease.
Imaging Assessments of ARPKD Kidney Disease Progression (IMAGE-ARPKD)
A study at Children's Hospital of Philadelphia using MRI to better understand how ARPKD kidney disease progresses over time.
Who can participate: Ages 6 and older with a clinical diagnosis of ARPKD, normal to moderately decreased kidney function (chronic kidney disease stages 1–3), no history of transplant, and able to safely have an MRI. Four study visits over about four years; travel costs are covered.
Interested, or want to learn more? Contact the Children's Hospital of Philadelphia study team: ARPKD_Studies@chop.edu
Liver-MAP: ARPKD Liver Imaging Study
A study at Children's Hospital of Philadelphia testing whether new MRI and ultrasound techniques can measure how severely the liver is affected in people with ARPKD.
Who can participate: Ages 6 and older with a clinical diagnosis of ARPKD who can lie in an MRI scanner for up to 60 minutes. Four study visits over about four years (about three hours each); participants are compensated for their time and travel.
Interested, or want to learn more? Contact the Children's Hospital of Philadelphia study team: ARPKD_Studies@chop.edu · 267-425-5541
ARPKD Transitions Study
An interview study at Children's Hospital of Philadelphia exploring what it is like to live with ARPKD and to move from pediatric to adult care — from both the patient and the parent/guardian perspective.
Who can participate: A single one-on-one online interview of about 60 minutes (with a short demographic survey beforehand); participants are compensated. Open to patients ages 16–30 with ARPKD, and to parents and guardians of adolescents and young adults ages 16–30.
Interested, or want to learn more? Contact the Children's Hospital of Philadelphia study team: ARPKD_Studies@chop.edu
Please note: The NIH Natural History Study — Clinical Investigations into Autosomal-Recessive Polycystic Kidney Disease and Congenital Hepatic Fibrosis — has finished and is now closed to new participants. Learn about its findings on our Landmark NIH Study page.
Looking for more?
To see additional research trials — including studies outside the United States — search ClinicalTrials.gov. For published medical literature, search PubMed.