What is autosomal recessive polycystic kidney disease (ARPKD)

Autosomal recessive polycystic kidney disease (ARPKD) is a rare disease that about 1 in every 20,000 babies are born with. It can cause many small fluid-filled sacs (cysts) and scar tissue to form in the kidneys. It can also cause scar tissue, cysts and other changes in the liver.  

ARPKD can affect people differently. Some people with ARPKD have mainly kidney problems, while others have mainly liver problems. The reason for this variation is not known.

The severity of the disease also varies:

• In the mildest cases, ARPKD does not cause symptoms until childhood or even adulthood. These people will have some health issues but are likely to live long lives.
• In the most severe cases, babies are born with serious lung and kidney problems. Sadly, about 3 in every 10 of these babies will not survive.

Before birth

Sometimes, signs of ARPKD are found while a baby is growing in the womb. These can show up on a routine pregnancy scan at about 18–21 weeks.

Signs are one or more of the following:

• An ultrasound scan showing large kidneys with cysts in them or both kidneys looking ‘bright’
• low levels of amniotic fluid (the fluid in the womb that cushions the baby)

Low levels of amniotic fluid are a sign the kidneys are not working well. This can affect lung development too.

Babies with signs of ARPKD before birth are likely to need specialist medical care as soon as they’re born. Parents-to-be will receive support and advice on what to expect and the best place for the birth.

Newborn babies

Health problems in babies with ARPKD can include:

• poor lung function in newborns, meaning a ventilator is needed
• low kidney function (which, if severe, requires dialysis)
• high blood pressure
• liver changes
• difficulty feeding (in part because the stomach and gut might be squashed by large kidneys and liver)
• particular facial features, twisted feet (club feet) and hip problems
•  

Not all babies with ARPKD will have these problems. Most babies with ARPKD survive to adulthood. Sadly, those with the weakest lungs might not survive the first days or weeks of life.

Children

We list symptoms of ARPKD in children below. It’s unlikely a child would have all of these problems: they vary over time and from child to child [PKDC AR child].

Kidney problems:

• reduced kidney function
• large kidneys
• infections of the urinary tract (bladder, kidneys and connecting tubes)
• peeing much more than usual, which can include bedwetting.

Blood problems:

• low numbers of red blood cells in the blood (anaemia)
• low sodium in the blood
• too much acid in the blood
• high blood pressure.

Liver problems:

• a large liver
• a wide bile duct (which sends bile from the liver to the gut). This can affect digestion and get infected (cholangitis).
• high blood pressure in the vein to the liver (portal hypertension). This can lead to a large spleen, fluid in the abdomen, and swollen blood vessels in the oesophagus (gullet) and gut.

Nutrition and growth problems:

• not eating well (partly because enlarged kidneys/liver can squash the stomach and gut)
• being underweight
• slower development.

Psychological problems:

• difficult emotions
• behavioural and attention challenges.

What can be done about ARPKD?

Tests

ARPKD can be diagnosed based on an ultrasound scan (sometimes even before birth). A genetic test can be used to confirm the diagnosis.

People with ARPKD have a team of experts who check their health regularly.

Checks typically include:

• scans to check the kidneys and liver
• blood and urine tests to check how well the kidneys and liver are working
• blood pressure checks
• chats about how children are getting on at school, at home and in clubs.

Treatments

The treatments that newborns, babies and children with ARPKD need depends on how the disease is affecting them.

Treatments can include:

• a ventilator (breathing machine) for newborns whose lungs are not fully developed
• medicines to control blood pressure
• medicines to treat anaemia
• diet changes or medicines to control acid levels in the blood
• antibiotics for infections
• a feeding tube (gastrostomy) for babies and children who are not eating enough
• supplements to aid digestion
• dialysis or a kidney transplant if the kidneys fail
• removal of one or both kidneys if they’re causing problems
• procedures, surgery, or a liver transplant to treat problems related to portal hypertension
• growth hormones for children who are small for their age.

Steps to keep children healthy

Parents can help children with ARPKD to stay healthier and happier by:

• making sure they drink enough fluid to stay hydrated
• giving reassurance about bedwetting
• chatting to the school about their child’s needs
• being alert for signs of infections (such as a high temperature, pain, and crying in babies)
• going to all recommended check-ups.

Other people’s experiences

The PKD Charity gives patients a number of ways to connect with each other and share experiences. This includes face-to-face information days, online events, and a Facebook group for ARPKD support. Call our helpline on 0300 111 1234.

How the disease works

ARPKD genes

ARPKD is caused by altered genes (gene mutations). The disease usually occurs when a child inherits altered PKHD1 genes from both their mother and father. Less commonly, it is caused by altered DZIP1L genes.

We all have thousands of different genes. These act as recipes for different proteins that our bodies need to grow and work.

The PKHD1 gene is for a protein called fibrocystin. This protein is found on cells that line tubes in the kidneys and liver. It’s not well understood how an altered PKHD1 gene leads to the changes seen to the kidneys and liver in ARPKD.

How is it inherited?  

Whether or not a person has ARPKD or can pass it to their children depends on whether they have altered copies of the genes linked to ARPKD:

• A person with two normal copies of PKHD1 (and DZIP1L) is healthy.
• A person with one altered copy of PKHD1 (or DZIP1L) is a carrier. They don’t have ARPKD but they can pass on the altered gene to a child.
• A person with two altered copies of PKHD1 (or DZIP1L) has ARPKD.

About 1 in every 70 people in the UK is a carrier of an ARPKD gene.

ARPKD occurs when 2 carriers have a baby who inherits an altered gene from each parent. For 2 carrier parents, there is a 1 in 4 chance of this happening. This pattern is called ‘autosomal recessive’ inheritance. We show it in the figure below using PKHD1 as the example.

Figure 1: How ARPKD genes are passed from parents to their child. Both of the parents in this example have one normal PKHD1 gene (green) and one mutated copy (purple). This means that each of them is a carrier, although they don’t have ARPKD themselves. If these 2 people have a baby, there is a 1 in 4 chance the baby will inherit a mutated gene from each parent (bottom left). This child will have ARPKD. There is a 2 in 4 chance the baby will inherit the normal gene from one parent and a mutated gene from the other. This baby will be healthy, but a carrier. There is a 1 in 4 chance the baby will inherit 2 normal copies of the gene (bottom right). This baby will be healthy and can’t pass on ARPKD.

What’s new? Opportunities for research and development

The ARPKD Rare Disease Group and international partners are aiming to find new and improved treatments for ARPKD and empower patients.

A first step is to collect information on:

• symptoms
• treatment choices
• markers (things you can measure in tests that help to plan treatment).

To do this the group is registering people with ARPKD in the National Rare Kidney Disease Registry (RaDaR). The database will be used to find suitable participants for future research and clinical trials of potential new treatments for ARPKD.

If you’re interested in finding out more about the RaDaR or the activity of the Rare Disease Group, please visit the ARPKD RDG page.