Autosomal Recessive Polycystic Kidney Disease

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Introduction

Autosomal Recessive Polycystic Kidney Disease

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 peeing 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.

Read more about the symptoms of ARPKD and diagnosing ARPKD.

Even though ARPKD is rare, it's one of the most common kidney problems to affect young children. It's estimated that around 1 in 20,000 babies is born with the condition. Both boys and girls are affected equally.

What causes ARPKD?

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

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

Over time, the cysts cause the kidneys to become enlarged and scarred (fibrosis), resulting in the deterioration of overall kidney function.

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 is caused by 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's a one in four (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. ADPKD can be inherited if only one parent carries one of the genetic faults responsible for the condition.

Read more about the causes of ARPKD.

Treating ARPKD

There's currently no cure for ARPKD, but various treatments can help manage the wide range of problems it 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.

More than half of all children who survive the early stages of ARPKD will eventually experience kidney failure by the time they're 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

Read more about the treatment of ARPKD.

Outlook

The outlook for children with ARPKD can vary considerably, depending on the severity of the condition.

If routine scans pick up kidney problems during pregnancy, the baby will usually have a poorer outlook than a child who's diagnosed at a later stage.

However, in general, ARPKD is a severe condition and around one in three babies will die from severe breathing difficulties during the first four weeks after birth.

About eight or nine out of 10 babies (80-90%) with ARPKD who survive the first month of life will live until they're at least five years old.

It's difficult to predict exactly how long a child with ARPKD will live because there's very little data showing long-term survival rates. However, with advances in treatments and a better understanding of the condition, increasing numbers of children with ARPKD are living well into adulthood.

Information about you

If you have ARPKD, your clinical team will pass information about you on to the National Congenital Anomaly and Rare Diseases Registration Service (NCARDRS).

This helps scientists look for better ways to prevent and treat this condition. You can opt out of the register at any time.

Find out more about the register.


Symptoms

Symptoms

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 the condition, an ultrasound scan may show that:

  • they have enlarged or "bright" kidneys
  • their lungs are underdeveloped
  • there's 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 caused by the lungs being underdeveloped
  • a swollen abdomen (tummy) - caused by enlargement of the kidneys
  • Potter's syndrome - where a lack of amniotic fluid leads to deformities of the limbs, face and ears; Potter's syndrome is a possibility in severe cases of ARPKD 

Underdeveloped lungs is the biggest problem immediately after birth and breathing assistance with a ventilator is often needed. A ventilator is a machine that moves air in and out of the lungs.

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.

If a baby survives this stage, the chance of long-term survival is much better and around 90% of those who survive these early stages will live for 10 years. However, about a third of these children will need 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 for children with ARPKD.

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

Liver problems and internal bleeding

For 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, particularly in the lower gullet (oesophagus) and if they get too big they can bleed.

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

An enlarged spleen may remove too many of these cells, including platelets, which can increase the risk of internal bleeding, particularly from any varices that have developed. Platelets are tiny cells that cause the blood to thicken (clot) if a blood vessel is damaged.

Internal bleeding 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 form 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 - passing large amounts of urine, which means your child will need to urinate frequently and may wet the bed
  • polydipsia - an excessive and prolonged thirst

These symptoms increase 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:

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 their enlarged kidneys take 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 their stomach, either through the nose or abdomen.

Faltering growth

Some children with ARPKD don't grow at a normal rate. Doctors call this faltering growth or failure to thrive, and it's 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're having feeding problems.

Chronic kidney disease and kidney failure

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

CKD doesn't usually cause any symptoms until it's reached an advanced stage.

The most advanced stage of CKD is known as 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 (oedema)
  • shortness of breath
  • an increased need to urinate, particularly at night (nocturia)
  • itchy skin
  • feeling sick

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


Causes

Causes

Autosomal recessive polycystic kidney disease (ARPKD) is an inherited condition, which means it's passed on to a child from their parents.

ARPKD is caused by a DNA mutation (abnormality) in a gene called PKHD1, which produces a protein called fibrocystin that gives the kidney its structure. The faulty PKHD1 gene is responsible for small fluid-filled sacs (cysts) and scarring developing in the kidneys.

In some cases, the faulty gene can also cause enlargement and scarring of the liver, 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 the bile ducts become 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 that 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 won't develop ARPKD, but will carry the mutated gene. It's estimated that 1 in 70 people in the UK is a carrier of the mutated PKHD1 gene.

If you're a carrier of the mutated gene and you conceive a baby with a partner who's also a carrier, there's a:

  • 25% chance the baby will receive a pair of normal genes
  • 50% chance the baby will receive one normal gene and one mutated gene, and become a carrier of the PKHD1 mutation
  • 25% chance the baby will receive a pair of mutated genes and develop ARPKD

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

Read more about diagnosing ARPKD.


Diagnosis

Diagnosis

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're considering having a baby, you may be referred to a genetic counsellor to discuss your options in terms of the tests that can be carried out before and during pregnancy.

A genetic counsellor can also discuss the possibility of pre-implantation genetic diagnosis. This is where a couple who are both carriers of the ARPKD gene use in vitro fertilisation (IVF) to conceive and the embryos are tested for ARPKD before they're implanted into the womb.

During pregnancy

In some cases, it may be possible to detect ARPKD during routine ultrasound scans. The kidneys of a baby with ARPKD may appear unusually large or bright on the scan.

Early signs of ARPKD are sometimes visible during the first routine ultrasound scan carried out at week 12 of pregnancy, although the condition isn't usually 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 whether you both carry the faulty gene that causes the condition (PKHD1). ARPKD can only be passed on to a child if both parents carry the faulty PKHD1 gene.

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

Following birth

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

  • 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 
  • blood test to assess kidney function

Genetic testing for the faulty PKHD1 gene that causes ARPKD may also help support a diagnosis, but it isn't routine and is usually only carried out if doctors think there's a possibility that a child's symptoms could be caused by a condition other than ARPKD.

Treatment

Treatment

There's 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:

Treatments for these common problems are described below.

Breathing difficulties

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

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

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

They may also be given a type of medication called 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 (the 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 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

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:

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 angiotensin 2 receptor blockers (ARBs), which work in a similar way to ACE inhibitors, but don't cause a cough.

As well as 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.

Read more about treating high blood pressure.

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 that 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 can burst under high blood pressure.

If your child has bleeding from these varices, urgent treatment will be needed 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 has particularly severe liver problems, they may need a liver transplant. If they also need a kidney transplant, both procedures may be combined into a single operation.

Chronic kidney disease

If your child's condition progresses to a stage where their kidney function is significantly affected, they'll 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 iron in the body, which leads to a decreasing number 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, which is taken with meals 
  • growth problems - which can be treated with injections of human growth hormone (HGH), a synthetic version of the hormones used by the body to stimulate growth

Read more about treating chronic kidney disease.

Kidney failure

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

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

When kidney failure occurs, your child will need to have their kidneys replaced or treatment to compensate for their loss of kidney 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 living or recently deceased donor and implanted into a person with kidney failure

A person only needs one kidney to survive, so 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're 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.