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Introduction 

Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited childhood condition where the development of the kidneys and liver is abnormal. Over time, either one of these organs may fail.

The condition often causes serious problems soon after birth, although less severe cases may not become obvious until a child is older.

ARPKD can cause a wide range of problems, including:

  • underdeveloped lungs, which can cause severe breathing difficulties soon after birth

  • high blood pressure (hypertension)

  • excessive urination and thirst

  • problems with blood flow through the liver, which can lead to serious internal bleeding

  • a progressive loss of kidney function, known as chronic kidney disease (CKD)

When these problems develop, and how severe they are, can vary considerably – even between family members with the condition.

What causes ARPKD?

ARPKD is caused by a genetic fault that disrupts normal development of the kidneys and liver.

In particular, the development and growth of the small tubes (tubules) that make up the kidneys is affected, causing bulges and cysts (fluid-filled sacs) to develop within them.

Over time, the kidneys become enlarged and scarred (fibrosis) as a result of the cysts, causing overall kidney function to deteriorate.

Similar problems also affect the small tubes (bile ducts) that allow bile (a digestive fluid) to flow out of the liver. The bile ducts may develop abnormally and cysts may grow inside them. The liver can also become scarred over time.

ARPKD occurs as the result of a genetic alteration in the gene PKHD1, which in most cases is passed on to a child by their parents. If both parents carry a faulty version of this gene, there is a 25% chance of each child they have developing ARPKD.

The way ARPKD is inherited is different from a more common type of kidney disease called autosomal dominant polycystic kidney disease (ADPKD), which usually doesn't cause significantly reduced kidney function until adulthood. This can be inherited if only one parent carries one of the genetic faults responsible for the condition.

Who is affected?

Although ARPKD is one of the most common kidney problems to affect young children, it is still rare.

It's estimated that between 1 in 10,000 and 1 in 40,000 babies is born with ARPKD. Both boys and girls are affected equally.

How ARPKD is treated

There is currently no cure for ARPKD, but various treatments are available to help manage the wide range of problems the condition can cause.

Treatment for ARPKD may include:

  • breathing assistance with a ventilator (a machine that moves air in and out of the lungs) for children with severe breathing difficulties

  • medication to treat high blood pressure

  • procedures to stop any internal bleeding that may occur

  • medications to control problems associated with the loss of kidney function, such as iron supplements for anaemia (a lack of red blood cells)

More than half of the children who survive the early stages of the condition after birth will eventually experience kidney failure by the time they are 15 to 20 years old.

If kidney failure does occur, there are two main treatment options:

  • dialysis – where a machine is used to replicate many functions of the kidney

  • kidney transplant – where a healthy kidney is removed from a living or recently deceased donor and implanted into someone with kidney failure

Outlook

The outlook for ARPKD can vary considerably between different people with the condition.

Despite the best efforts of medical teams, around one in every three children born with severe breathing difficulties will die as a result of the condition.

For those children who survive these early stages or who are diagnosed with ARPKD when they are older, the outlook is generally better.

It's estimated that around 90% of these children will live until they are at least 10 years old and, with advances in treatment, increasing numbers of people with the condition are living well into adulthood.

 

 

 

ARPKD often causes serious problems soon after birth 

 

The kidneys

The kidneys are two bean-shaped organs located on either side of the body, just beneath the ribcage.

The main role of the kidneys is to filter out waste products from the blood before passing them out of the body as urine. The kidneys also help maintain blood pressure at a healthy level.

Symptoms of autosomal recessive polycystic kidney disease 

The symptoms of autosomal recessive polycystic kidney disease (ARPKD) can vary significantly, even within the same family.

Generally, however, the main symptoms of ARPKD differ depending on when the condition first becomes apparent.

Before and soon after birth

In many cases, potential signs of ARPKD can be detected before birth during routine ultrasound scans. If your baby has ARPKD, an ultrasound scan may show that:

  • your baby has enlarged or "bright" kidneys

  • your baby's lungs are underdeveloped

  • there is a lack of amniotic fluid surrounding your baby 

When your baby is born, there may be clearer signs that suggest they have ARPKD, such as:

  • significant breathing difficulties – this is a result of the underdevelopment of the lungs

  • a swollen abdomen (tummy) – caused by enlargement of the kidneys

  • Potter's syndrome – a possibility in severe cases, when a lack of amniotic fluid leads to deformities of the limbs, face and ears

Immediately after birth, underdeveloped lungs are the biggest problem and breathing assistance with a ventilator (a machine that moves air in and out of the lungs) is often needed immediately.

Unfortunately, even with treatment, around one in every three babies with ARPKD who develop breathing difficulties soon after birth will die within a few weeks or months.

However, if a baby survives this stage, the chance of long-term survival is much better. Around 90% of newborn babies who survive these early stages will be alive 10 years later, although a third of these children will require treatment for kidney failure.

Infants and children

ARPKD tends to be less immediately life-threatening in infants and older children, although the condition can still cause a wide range of serious problems.

Some of the main problems infants and children with ARPKD experience are described below.

High blood pressure

High blood pressure (hypertension) is a common problem in children with ARPKD.

If your child has high blood pressure, they will usually need to take medication to lower it and prevent long-term damage to their heart and blood vessels. 

Liver problems and internal bleeding

In children with ARPKD, a number of problems affecting the liver can also develop. For example, the small tubes (bile ducts) that allow bile (a digestive fluid) to flow out of the liver may develop abnormally and cysts may grow inside them.

Over time, the liver can also develop fibrosis, a process similar to scarring. This restricts the blood flow through the liver and increases the pressure in its delicate blood vessels (portal hypertension).

When this occurs, blood bypasses the liver and is diverted into veins. These veins then become swollen (varices), particularly in the lower gullet (oesophageal varices). If they get beyond a certain size, they can bleed.

Portal hypertension also diverts blood to the spleen, causing it to become enlarged. This can affect the normal functions of the spleen, such as removing old or damaged blood cells from the blood.

An enlarged spleen may remove too many of these cells, including platelets (cell fragments in the blood that make the blood clot if a blood vessel is damaged), which can increase the risk of internal bleeding (internal haemorrhage), particularly from any varices that have developed.

If your child does experience any internal bleeding, this can be rapid and severe, causing your child to vomit blood or pass stools that are very dark or tar-like.

Excessive urination and thirst

In ARPKD, the small tubes (tubules) that make up the kidneys can develop abnormally, causing bulges and cysts (fluid-filled sacs) to develop within them.

The tubules are important in regulating how much water is held in the body. This is disrupted in ARPKD, which is why small children lose excessive amounts of body fluid as urine. This can lead to:

  • polyuria – where large amounts of urine are passed, which can mean your child needs to urinate frequently and may wet the bed

  • polydipsia – an excessive and prolonged thirst

This increases the risk of dehydration, particularly if the child also has a high temperature, is vomiting, or has diarrhoea.

Signs and symptoms of dehydration can include:

  • dry mouth and lips

  • sunken features (particularly the eyes)

  • headaches

  • dizziness

  • irritability

Contact your child's kidney specialist if you think your child may be becoming dehydrated, as regular dehydration treatments, including oral rehydration treatments such as Dioralyte, may not be suitable for them.

Feeding problems

Your child may have problems feeding because of the very large kidneys taking up most of the space in their abdomen. They may vomit after eating and may only be able to eat small amounts at a time.

If this leads to malnourishment, your child may need to be fed through a tube inserted into the stomach, either through the nose or the abdomen.

Faltering growth

Some children with ARPKD do not grow at a normal rate. Doctors call this faltering growth or failure to thrive, and this is usually caused by a combination of factors.

Children with ARPKD are usually under the care of a dietitian, who may recommend a high-calorie and high-protein diet to boost their weight. Some children may also need to be fed through a tube if they are having feeding problems.

Chronic kidney disease and kidney failure

Most people with ARPKD will lose a significant amount of kidney function. Loss of kidney function caused by kidney damage is known as chronic kidney disease (CKD).

CKD does not usually cause any symptoms until it has reached an advanced stage.

The most advanced stage of CKD is called kidney failure or end-stage renal disease. This occurs when the kidneys have lost almost all of their ability to function.

Symptoms of kidney failure can include:

  • poor appetite and weight loss

  • swollen ankles, feet or hands

  • shortness of breath

  • an increased need to urinate, particularly noticeable at night

  • itchy skin

  • feeling sick

Most children with ARPKD will develop kidney failure by the time they are 15 to 20 years old, and they will need either a kidney transplantor dialysis (where a machine is used to replicate many of the functions of the kidneys).

Causes of autosomal recessive polycystic kidney disease 

Autosomal recessive polycystic kidney disease (ARPKD) is caused by a DNA mutation in a gene called PKHD1.

In ARPKD, the faulty PKHD1 gene causes small fluid-filled sacs (cysts) and scarring to develop in the kidneys.

In some cases, the faulty PKHD1 gene can also cause the liver to become enlarged and scarred, or the bile ducts (which produce a digestive fluid called bile) to widen.

This can make it difficult for blood to flow through the liver and can make the bile duct more vulnerable to infection.

The genetic fault responsible for ARPKD is usually passed on to a child by their parents. 

How ARPKD is inherited

The mutation that causes ARPKD is known as an autosomal recessive mutation. This means a baby needs to receive two copies of the mutated gene to develop the condition – one from their mother and one from their father.

If a baby only receives one copy of the mutated gene from one of their parents, he or she will not develop ARPKD but will carry the mutated gene. It is estimated that 1 in 70 people in the UK is a carrier of the mutated PKDH1 gene.

If you are a carrier of the mutated gene and you conceive a baby with a partner who is also a carrier, there is:

  • a 25% chance the baby will receive a pair of normal genes

  • a 50% chance the baby will receive one normal gene and one mutated gene and become a carrier of the PKHD1 mutation

  • a 25% chance the baby will receive a pair of mutated genes and develop ARPKD

If you have a family history of ARPKD and you are considering trying for a baby, your GP may refer you to a geneticist or genetic counsellorto discuss the risks, benefits and limitations of testing for the condition.

Diagnosing autosomal recessive polycystic kidney disease 

A diagnosis of autosomal recessive polycystic kidney disease (ARPKD) is usually based on a child's symptoms and the results of an ultrasound scan.

Before getting pregnant

If you have a family history of ARPKD and you are considering having a baby, you may be referred to a genetic counsellor to discuss what your options are in terms of the tests that can be carried out before and during pregnancy.

A genetic counsellor may also talk to you about the possibility of pre-implantation genetic diagnosis. This involves a couple who are both carriers of the ARPKD gene undergoing in-vitro fertilisation (IVF) to conceive and then having the embryos tested for the condition before implanting them in the womb.

During pregnancy

In some cases, it may be possible to detect ARPKD during routine ultrasound scans. If your baby has ARPKD, their kidneys may appear unusually large or bright on the scan.

Early signs of ARPKD may sometimes be visible during the first routine ultrasound scan carried out when you are around 12 weeks pregnant, although the condition is not usually first detected until the second routine scan at around 20 weeks.

If you have a known family history of ARPKD, it may be possible to be more certain about the diagnosis by testing your and your partner's blood to see if you both carry the faulty gene that causes the condition. ARPKD can only be passed on to a child if both parents carry this faulty gene.

It is also possible to test the foetus for the genetic mutation, but this involves invasive procedures such as chorionic villus samplingor amniocentesis, which carry a risk of miscarriage.

Following birth

Tests that can be used to help diagnose ARPKD after birth are:

  • a physical examination to look for visible signs of ARPKD, such as a swollen abdomen (tummy)

  • blood pressure monitoring

  • an ultrasound scan of the kidneys 

  • a blood test to assess kidney function

Genetic testing for the faulty gene that causes ARPKD may also help support a diagnosis, although this is not routine and is usually only carried out if doctors think there is a possibility a child's symptoms could be caused by a condition other than ARPKD.

Treating autosomal recessive polycystic kidney disease 

There is currently no cure for autosomal recessive polycystic kidney disease (ARPKD).

However, treatments are available to manage the condition's associated symptoms and any complications that may occur, such as:

  • breathing difficulties caused by underdeveloped lungs (pulmonary hypoplasia)

  • high blood pressure

  • liver problems

  • chronic kidney disease (CKD) and kidney failure 

Treatments for these common problems are described below.

Breathing difficulties

If there is thought to be a significant risk your baby will be born with underdeveloped lungs (pulmonary hypoplasia), particularly if your baby is premature, treatment can begin before they are born.

You may be injected with a medication called betamethasone during your pregnancy. This helps to stimulate the development of your baby's lungs and help them work more efficiently if they are born prematurely.

After birth, it is likely your baby will be immediately admitted to an intensive care unit (ICU), where they will be placed on a ventilator (an artificial breathing machine) to assist their breathing.

They may also be given a type of medication known as a surfactant, which helps prevent tiny air sacs inside the lungs known as alveoli collapsing. The more working alveoli your baby has, the better their ability to breathe.

Breathing difficulties can be made worse if your baby's enlarged kidneys press on their diaphragm (a sheet of muscle in the abdomen that helps with breathing). In a few cases, the doctor treating your baby may recommend removing one of their kidneys to relieve the pressure.

Despite advances in treatment, pulmonary hypoplasia is still a very difficult condition to manage in babies with ARPKD. In some cases, your baby may need to stay in hospital for weeks or months. Even with the best efforts of the medical team, around one in every three babies will die as a result of the condition. 

High blood pressure

A type of medication called an angiotensin-converting enzyme (ACE) inhibitor is the most widely used treatment for babies and children with high blood pressure.

ACE inhibitors reduce blood pressure by reducing the pressure across the filtering units of the kidney (glomeruli).

Possible side effects of ACE inhibitors can include:

  • dizziness

  • tiredness or weakness

  • headaches

  • a persistent dry cough

  • high potassium levels or worsening of the kidney function (blood tests are needed to monitor this)

Most of these side effects should pass in a few days, although some people have a dry cough for longer.

A similar group of blood pressure medicines are angiotension II receptor blockers (ARBs), which work in a similar way to ACE inhibitors but do not cause a cough.

In addition to ACE inhibitors and ARBs, there are lots of other medications that may also be used to control blood pressure in children with ARPKD, such as calcium channel blockers, beta-blockers and diuretics.

 

Liver problems

Many children with ARPKD also have problems affecting their liver, such as swelling and scarring.

Scarring in the liver can make it difficult for blood to flow through it, and this can mean blood is forced through blood vessels in your child's stomach or gullet (oesophagus) instead.

These blood vessels, known as varices, are smaller and more fragile than the blood vessels in the liver and they can burst under high blood pressure.

If your child experiences bleeding from these varices, they will need urgent treatment to stop the bleeding. This will usually involve passing a thin, flexible tube called an endoscope down their mouth and gullet (oesophagus), and either placing a small band around the base of the varices or injecting a special medication "superglue" to make the blood clot.

If your child's liver problems are particularly severe, they may need to have a liver transplant. If your child needs a kidney transplant as well, these may be combined into a single procedure.

Chronic kidney disease

If your child's condition progresses to a stage where their kidney function is significantly affected, they will usually need a number of different treatments to manage the various problems this can cause.

For example, your child may need treatment for the following problems:

  • anaemia (a lack of red blood cells) – this can be treated with iron supplements, injections of erythropoietin (the hormone the kidneys produce to stimulate red blood cell production), or blood transfusions in severe cases

  • high phosphate levels, which can affect bone health – this can be treated with a medication called a phosphate binder that is taken with meals 

  • growth problems – this can be treated with injections of human growth hormone (HGH), a synthetic version of the hormones used by the body to stimulate growth

Kidney failure

Most people with ARPKD will eventually develop kidney failure at some point in their life. 

More than half of children who survive the early stages of the condition after birth will eventually experience kidney failure by the time they are 15 to 20 years old.

When this does occur, your child will need treatment to replace their kidneys or compensate for their loss of function.

There are currently two effective treatments that can be used on a long-term basis:

  • dialysis – where a machine replicates many functions of the kidneys

  • kidney transplant– where a kidney is removed from a donor and implanted into a patient

A kidney donor can be somebody who is recently deceased or, as is increasingly common, someone who is still alive.

A person only needs one kidney to survive. This means that unlike many other types of organ donation, a living person can donate a kidney.

Close relatives usually make the best match, so you may want to consider getting yourself tested to see if you are a suitable candidate for donation.

You could also ask your relatives if they would consider having themselves tested to see if they could donate one of their kidneys.

Polycystic kidney disease autosomal recessive ARPKD

Polycystic kidney disease autosomal recessive ARPKD