Autosomal Recessive Polycystic Kidney Disease (ARPKD)
DISEASE DEFINITION
Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder that primarily affects the kidneys and the liver and is characterized with formation and uncontrolled growth of fluid-filled cysts in the kidney, the spread of which eventually leads to the loss of kidney function.
GENETICS OR INHERITANCE OF ARPKD
ARPKD is inherited in an autosomal recessive manner, which means that both parents must carry a mutated copy of the responsible gene for their child to develop the condition. If both parents are carriers of the ARPKD gene mutation, there is a 25% chance with each pregnancy that their child will have ARPKD.
The disease develops during prenatal development, or in early childhood. It is often diagnosed in infancy or childhood, but the severity and onset of symptoms can vary widely among affected individuals. The primary cause of ARPKD is mutations in the PKHD1 gene encoding the fibrocystin. The fiborcystin is localized in the primary cilia and basal bodies in kidney epithelial cells and participates in the organization of microtubules and/or mechano-and chemo-sensibilization of primary cilia, as well as in regulation of intracellular adhesion and cell proliferation.
► ARPKD is a complex and challenging condition that requires ongoing medical care and support.
SYMPTOMS
The clinical presentation of ARPKD can vary widely. Common symptoms and complications may include enlarged kidneys, high blood pressure, urinary tract infections, abdominal pain, and liver problems.
The early signs of ARPKD often appear during the first few months of life and in the womb. Early signs of ARPKD in the womb can cause serious health problems. For this reason, it is important for a woman who is at risk for passing PKD to her children to get prenatal care as soon as she learns she is pregnant.Some people with ARPKD do not develop signs or symptoms until later in childhood, or even adulthood.
Enlarged kidney
An early sign of ARPKD is an enlarged kidney. Enlarged kidneys put pressure on a fetus’ or child’s lungs, which can make lung growth and breathing harder. A health care provider can see enlarged kidneys in a fetus or an infant using ultrasound imaging, also called a sonogram.
Growth failure
Due to decreased kidney and lung function, children with ARPKD are usually smaller-than-average size, a condition called growth failure.
Low levels of amniotic fluid
Decreased kidney function can cause prenatally low levels of amniotic fluid in a mother’s womb. Low levels of amniotic fluid can cause lung hypoplasia and with it connected breathing problems. The extent of pulmonary hypoplasia after oligo-/anhydramnios is crucial for prognosis in the first days of life.
Kidney Function Impairment
ARPKD can lead to progressive damage to the kidneys, resulting in impaired kidney function over time.
Kidney Cysts
Cysts in the kidneys are a hallmark of ARPKD. These cysts can cause the kidneys to become enlarged and dysfunctional.
Gastrointestinal Symptoms
Some individuals with ARPKD may experience gastrointestinal issues such as poor appetite, vomiting, or diarrhea.
Jaundice
Yellowing of the skin and eyes (jaundice) may occur due to liver involvement.
What are the complications of ARPKD?
Children with ARPKD who survive birth often have kidney and liver problems that can affect their breathing. Working with a health care team as soon as possible can help manage these complications.
Breathing problems
Babies with the most severe cases of ARPKD often die hours or days after birth because they cannot breathe well enough to live. Their lungs do not develop as they should in the womb.
Kidney Enlargement (Nephromegaly)
Cysts form in the kidneys, causing them to enlarge and lose function over time.
Kidney Failure
The progressive loss of kidney function can lead to kidney failure, which may require dialysis or kidney transplantation, before reaching adulthood.
Hyponatremia
As mentioned in a previous response, low sodium levels in the blood (hyponatremia) can occur due to kidney dysfunction in ARPKD.
Urinary Tract Infections
Recurrent urinary tract infections can occur due to the kidney and urinary tract abnormalities associated with ARPKD.
High blood pressure
Most children with ARPKD have high blood pressure. High blood pressure increases a child’s chances of heart disease and stroke. High blood pressure can also further damage a child’s kidneys.
Heart Valve Abnormalities
Some individuals with ARPKD may develop heart valve abnormalities.
Liver Involvement
ARPKD can also affect the liver, causing fibrosis (the formation of scar tissue) in the liver's bile ducts. This can lead to liver problems, including hepatomegaly (enlarged liver) and, in severe cases, liver failure. Liver fibrosis can lead to increased pressure in the portal vein (portal hypertension), which can result in complications such as bleeding from esophageal varices.
Growth and Developmental Delays
Infants and children with ARPKD may experience growth and developmental delays, possibly due to chronic illness and nutritional issues.
Cognitive and Behavioral Challenges
Some individuals with ARPKD may face cognitive and behavioral challenges, which can vary in severity. These challenges can be related to chronic illness, medications, or other factors.
Neurological Complications
In rare cases, ARPKD can be associated with neurological complications, including seizures.
DIAGNOSIS
Prenatal ultrasound
ARPKD may be suspected due to the routine prenatal ultrasound examinations.
Postnatal ultrasound
After birth, an ultrasound is done to confirm the diagnosis and assess the extent of kidney and liver involvement.
Genetic testing
Genetic testing can confirm the presence of ARPKD mutations.
TREATMENT
There is no cure for ARPKD, but treatment focuses on managing the symptoms and complications. This may include medication to control blood pressure, dietary management, and, in severe cases of kidney failure, the need for kidney transplantation.
PROGNOSIS
The prognosis for people with ARPKD varies depending on the severity of the disease and the extent of kidney and liver involvement. Some children may have relatively good kidney function and a relatively normal life expectancy with appropriate medical care, while others may face more severe challenges. Kidney replacement therapy is required in about 50% of ARPKD patients in the first two decades of life. Peritoneal dialysis has been recommended as the dialysis modality of choice early in life.