Autosomal recessive polycystic kidney disease (ARPKD)

Page last reviewed: 13/07/2011

An autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic childhood condition.

In ARPKD, cysts (small fluid-filled sacs) grow on the kidneys and damage them. In some cases, ARPKD can also damage the liver in the same way.

The symptoms of ARPKD range from moderate to life-threatening, and include:

  • high blood pressure (hypertension)
  • excessive thirst
  • loss of normal lung function

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 converting them into urine. The kidneys also help to maintain blood pressure at a healthy level.

How common is ARPKD?

ARPKD is a rare condition. It is estimated that 1 in 20,000 babies is born with the condition.

The genetics of ARPKD

ARPKD is caused by a genetic mutation that is known as the PKHD1 mutation. A genetic mutation occurs when the normal instructions in certain genes become 'scrambled'. The PKHD1 mutation disrupts the normal development of the kidneys and, in some cases, the liver.

The PKHD1 mutation is an autosomal recessive mutation. This means that a person can carry the mutation without developing any symptoms. However, if two people who are both carriers have a baby, there is a 1 in 4 chance that the baby will develop ARPKD.

ARPKD can be cured using a kidney transplant (where a healthy kidney is transferred from one person to another). But this is not always possible or safe, particularly in children who are severely ill.

Types of ARPKD

There are four main types of ARPKD, which are classified in categories ranging from one to four. The lower the category number, the earlier symptoms begin and, usually, the poorer the outlook.

The four categories of ARPKD are described below below.

  • Category 1: the symptoms begin before birth and the baby is born with seriously underdeveloped lungs. Around 75% of babies who are born with this type of ARKPD will die within a week of birth, usually from complications arising from breathing difficulties.
  • Category 2: the symptoms develop in the first month after birth. This type of ARKPD usually causes a progressive loss of all kidney function (or almost all). The loss of kidney function is known as kidney failure or end-stage renal disease. Most babies with this type of ARKPD will die within a few months of birth from complications arising from kidney failure.
  • Category 3: the symptoms develop when a baby is a few months old. The most common symptoms are high blood pressure(hypertension) and chronic kidney disease (CKD - the kidneys lose a significant amount of their normal functioning ability).
  • Category 4: the symptoms usually first develop between the ages of six months and five years. They include high blood pressure and liver disease (as with CKS, liver disease occurs when the liver loses a large amount of its ability to function).

As ARPKD is so rare, it is difficult to accurately estimate which category of the condition is the most widespread. However, category 1 ARPKD is thought to be the most common type, accounting for three out of every four cases.

Note that members of the same family can sometimes be born with different categories of the condition. It is not known why this is.

Outlook

The outlook for babies who are born with category 1 or 2 ARPKD is poor, and the majority of children with the condition die shortly after birth.

If a baby manages to survive for a month, the outlook improves significantly. For example, around 80% of children who live for more than a month will live into adulthood.

The outlook for category 3 or 4 ARPKD is significantly better, but most older children and adults will develop health problems related to high blood pressure, kidney disease or liver disease in later life. For example, tiredness and shortness of breath. 

Blood
Blood supplies oxygen to the body and removes carbon dioxide. It is pumped around the body by the heart.
Chronic
Chronic usually means a condition that continues for a long time or keeps coming back.
Cyst
A cyst is a fluid-filled sac or cavity in the body.
Genetic
Genetic is a term that refers to genes- the characteristics inherited from a family member.
Kidney
Kidneys are a pair of bean-shaped organs located at the back of the abdomen, which remove waste and extra fluid from the blood and pass them out of the body as urine.
Spine
The spine supports the skeleton, and surrounds and protects the delicate spinal cord and nerves. It is made up of 33 bones called the vertebrae.

Autosomal dominant polycystic kidney disease (ADPKD)

Autosomal dominant polycystic kidney disease (ADPKD) is a more common type of polycystic kidney disease than ARPKD.

Autosomal dominant polycystic kidney disease tends to affect older people (adults aged 30 or over). See the Health A-Z topic about , for more information.

Page last reviewed: 13/07/2011

Each category of autosomal recessive polycystic kidney disease (ARPKD) has a different pattern of symptoms. These are described below.

Category 1 ARPKD

The symptoms of category 1 ARPKD begin before birth. Around half of all cases diagnosed during routine ultrasound scans.

The kidneys are affected by the development of multiple cysts (small, fluid-filled sacs), which make the kidneys much larger than usual. This can make the unborn baby's abdomen (tummy) swollen, which can cause difficulties when delivering the baby.

Another serious symptom of category 1 ARPKD is that the lungs are seriously underdeveloped - a condition that is known as pulmonary hypoplasia.

To develop normally, the lungs require an amino acid called proline, which is produced by the kidneys. However, due to the damage caused by the cysts, the kidneys do not produce enough proline. This leads to the lungs being much smaller than normal. The underdevelopment of the lungs causes serious breathing difficulties, which usually prove to be fatal.

Category 2 ARPKD

The symptoms of category 2 ARPKD develop in the first month after birth. The kidneys may be enlarged, which can often be detected by touch. Lung function is usually unaffected, or mildly or moderately disrupted.

Additional damage to the liver caused by cysts can often occur, resulting in the symptoms of mild liver disease. These symptoms include:

  • tiredness and weakness
  • loss of appetite
  • weight loss
  • feeling sick
  • very itchy skin

The damage to the kidneys progresses rapidly, resulting in kidney failure and, in most cases, death.

Category 3 ARPKD

The symptoms of category 3 ARPKD usually develop a few months after birth, and include noticeably enlarged kidneys, liver and spleen. Other conditions associated with this category of ARPKD include:

  • high blood pressure (hypertension)
  • chronic kidney disease

Most children with category 3 ARPKD will develop kidney failure by the time they reach puberty, and they will need either a kidney transplant or dialysis. Dialysis is a type of treatment that involves replicating many of the functions of the kidneys, such as their blood filtering abilities.

Category 4 ARPKD

The symptoms of category 4 ARPKD usually develop during early childhood, between six months to five years of age.

In this form of ARPKD, kidney damage is mild. Only about 10% of the kidneys are affected by cysts. But damage to the liver tends to be more extensive than in other forms of the condition.

Portal hypertension is a common related condition that is caused by liver damage. It occurs when the blood pressure inside the liver has risen to a potentially serious level.

If the liver becomes scarred, it becomes harder for blood to move through it. This leads to a rise in blood pressure.

The blood must also find a new way of returning to your heart. It does this by opening up new blood vessels, usually along the lining of the stomach. These new blood vessels are known as varices. If the blood pressure keeps rising, it can become too high for the varices to cope with, causing the varices' walls to split and bleed.

This may cause moderate but long-term bleeding, which could lead to anaemia (a condition where the body does not have enough oxygen-carrying red blood cells).

Symptoms of anaemia include:

  • fatigue
  • breathlessness (dyspnoea)
  • pale skin
  • irregular heartbeat

Alternatively, the bleeding can be rapid and massive, causing you to:

  • vomit blood
  • pass stools that are very dark or tar-like

If you suspect that you or your child is experiencing massive internal bleeding, dial 999 immediately and ask for an ambulance.

Abdomen
The abdomen is the part of the body between the chest and the hips.
Bladder
The bladder is a small organ near the pelvis that holds urine until it is ready to be passed from the body.
Blood
Blood supplies oxygen to the body and removes carbon dioxide. It is pumped around the body by the heart.
Cyst
A cyst is a fluid-filled sac or cavity in the body.
High blood pressure
Hypertension is when the pressure of the blood in your bloodstream is regularly above 140/90 mmHG.
Kidney
Kidneys are a pair of bean-shaped organs located at the back of the abdomen, which remove waste and extra fluid from the blood and pass them out of the body as urine.
Liver
The liver is the largest organ in the body. Its main jobs are to secrete bile (to help digestion), detoxify the blood and change food into energy.
Stomach

The sac-like organ of the digestive system. It helps digest food by churning it and mixing it with acids to break it down into smaller pieces.

 

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Page last reviewed: 13/07/2011

Genetic mutation

Autosomal recessive polycystic kidney disease (ARPKD) is caused by a genetic mutation known as the PKHD1 mutation.

A genetic mutation occurs when the instructions that are carried in certain genes become 'scrambled'. This means that some of the body's processes do not work in the normal way.

A healthy kidney contains a large number of ducts (channels), which absorb some of the fluids that pass through the kidney. Due to the genetic mutation, some of the ducts begin to secrete (pass out) fluid instead of absorbing fluids.

The secreted fluid is rich in a type of protein called epidermal growth factor (EGF), which stimulates the growth of new cells.

The combination of the abnormal growths secreting fluid and EGF stimulating new cell growth will lead to many of the ducts becoming enlarged. In turn, this leads to the creation of a series of cysts, an often massive enlargement of the kidneys and a loss of normal kidney function. Depending on the type of ARPKD that you have, 10-90% of your ducts can be affected in this way.

The PKHD1 mutation sometimes has a similar effect on your bile duct. Your bile duct is made up of a series of tubes that start in your liver and connect to your gallbladder and small intestine.

The bile duct helps to move bile from your liver into your gallbladder, which is a small pouch that stores bile when it is not being used. Bile is a fluid that the digestive system uses to help break down fats. The bile is then passed from your gallbladder into your small intestine.

The PKHD1 mutation causes your bile duct to become enlarged, and the bile scars your liver (cirrhosis). If your liver becomes extensively scarred, you may develop liver disease.

Autosomal recessive mutation

All the genes in your body come in pairs. You receive one half of the pair from your mother and the other half from your father.

The mutation that causes ARPKD is an autosomal recessive mutation. This means that you need to receive two copies of the mutated gene in order to develop the condition - one from your mother and one from your father.

If you only receive one copy of the mutated gene from one of your parents, you will not develop ARPKD but you will carry the mutated gene. It is estimated that 1 in 70 people is a carrier of the mutated 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 1 in 4 chance that the baby will receive a pair of normal genes
  • a 1 in 2 chance that the baby will receive one normal gene and one mutated gene and become a carrier of the PKHD1 mutation
  • a 1 in 4 chance that the baby will receive a pair of mutated genes and develop ARPKD
Disease
A disease is an illness or condition that interferes with normal body functions.
Gene
Genes contain information that you inherit from your parents, such as eye or hair colour. They are carried by chromosomes.
Genetic
Genetic is a term that refers to genes - the characteristics inherited from a family member.
Kidney

Kidneys are a pair of bean-shaped organs located at the back of the abdomen, which remove waste and extra fluid from the blood and pass them out of the body as urine.

 

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Page last reviewed: 13/07/2011

Before birth

Around half of all cases of autosomal recessive polycystic kidney disease (ARPKD) are diagnosed in pregnancy, during the routine ultrasound scan. The condition is not usually detected until the second routine scan at around week 20 of the pregnancy.

The kidneys of the unborn baby will appear unusually bright on the scan. This is thought to be caused by too much fluid inside the kidney.

Following birth

Two tests that can be used to diagnosis ARPKD after birth are:

  • computerised tomography (CT) scan- a scanner is used to take a series of X-ray scans and a computer assembles them into a more detailed image
  • magnetic resonance imaging (MRI) scan - strong magnetic fields and radio waves are used to produce a detailed image of the inside of the body

GFR blood test

An effective way of assessing how well your kidneys or your child's kidneys are working is to calculate your glomerular filtration rate (GFR). GFR is a measurement of how many millilitres (ml) of waste products your kidneys can filter in one minute. A healthy pair of kidneys should be able to filter more than 90ml.

Calculating your GFR usually involves taking a blood sample and measuring the levels of a waste product called creatinine. If your creatinine levels are higher than normal, it may suggest that your kidneys are not filtering the blood as effectively as they should.

A very low GFR rate (15-29ml) suggests that your kidneys are close to failing.

Genetic testing

Genetic testing for ARPKD is currently only possible if you have a relative who has been diagnosed with ARPKD.

A sample of your relative's DNA (deoxyribonucleic acid) will be extracted from their blood and compared against a sample of your own DNA. DNA are molecules which contain genetic information that determine characteristics, such as your eye and hair colour.

Once the DNA samples have been taken, a technique called linkage analysis is used. In simple terms, this involves finding out where in the DNA your relative's genetic mutation occurs, and checking whether your own DNA has mutated in a similar place.

Abdomen
The abdomen is the part of the body between the chest and the hips.
Bile duct
The bile duct is the tube which carries bile from your liver to your gall bladder. Bile helps digest food.
Biopsy
A biopsy is a test that involves taking a small sample of tissue from the body so it can be examined.
Chorionic villus sampling
Chorionic villus sampling is a test during pregnancy to see if there are any genetic problems with the foetus. A small sample of tissue is taken from the placenta.
Cyst
A cyst is a fluid-filled sac or cavity in the body.
Intravenous
Intravenous (IV) means the injection of blood, drugs or fluids into the bloodstream through a vein.
Kidney
Kidneys are a pair of bean-shaped organs located at the back of the abdomen, which remove waste and extra fluid from the blood and pass them out of the body as urine.
Liver
The liver is the largest organ in the body. Its main jobs are to secrete bile (to help digestion), detoxify the blood and change food into energy.
MRI
MRI stands for magnetic resonance imaging. It is the use of magnets and radio waves to take detailed pictures of inside the body.
Tissue
Body tissue is made up of groups of cells that perform a specific job, such as protecting the body against infection, producing movement or storing fat.
Ultrasound scan
Ultrasound scans are a way of producing pictures of inside the body using sound waves.
X-ray

An X-ray is a painless way of producing pictures of inside the body using radiation.

 

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Page last reviewed: 13/07/2011

There is currently no direct cure for autosomal recessive polycystic kidney disease (ARPKD). Therefore, treatment focuses on the condition's associated symptoms and any complications that may occur, such as:

  • pulmonary hypoplasia (underdeveloped lungs)
  • high blood pressure (hypertension)
  • chronic kidney disease
  • liver disease

Pulmonary hypoplasia

If there is thought to be a significant risk that your baby will be born with pulmonary hypoplasia, 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 the lungs and help the lungs work more efficiently.

After birth, it is likely that your baby will be immediately admitted to an intensive care unit (ICU). 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 to prevent tiny air sacs inside the lungs, known as alveoli, from 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 muscle in the abdomen that helps with breathing). The doctor treating your baby may consider removing one of their kidneys to relieve the pressure.

Pulmonary hypoplasia is a very difficult condition to treat in babies with ARPKD. Despite the best efforts of the medical teams, an only one in four babies with the condition will survive longer than a week after they are born. 

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 (hypertension).

ACE inhibitors work by blocking the actions of some of the hormones that help to regulate blood pressure. By stopping these hormones from working, the medication reduces the amount of water in your child's blood and widens their arteries. Both of these will help to lower their blood pressure.

The side effects of ACE inhibitors include:

  • dizziness
  • tiredness or weakness
  • headaches
  • a persistent dry cough

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

See the Health A-Z topic about High blood pressure - treatment for more information.

Chronic kidney disease

If your child has chronic kidney disease, it is likely that they will develop anaemia. Anaemia is a condition where there is not enough oxygen-carrying red blood cells. Symptoms of anaemia include:

  • tiredness
  • lethargy (lack of energy)
  • shortness of breath (dyspnoea)
  • palpitations (irregular heartbeat)

The reason children with chronic kidney disease develop anaemia is because the kidneys are responsible for stimulating the growth of new red blood cells. To treat anaemia, some people with kidney disease may be given a blood transfusion, where blood is injected intravenously (into the vein) in hospital.

Most children with kidney disease will be given iron supplements because iron is needed for the production of red blood cells. To boost iron levels, iron may be given as tablets, such as daily ferrous sulphate tablets, or as occasional intravenous injections.

Your child may also be given an injection of erythropoietin (a hormone that produces red blood cells) to help raise the amount of red blood cells in their body. These injections are often administered intravenously or subcutaneously (under the skin).

Examples of erythropoietin injections include epoetin alfa, which is given once a week, and darbepoetin alfa, which is given three times a week.

Your child is also likely to have increased levels of the mineral phosphate in their blood. Phosphate is obtained through diet, mainly through dairy foods.

Healthy kidneys usually filter out any excess phosphate. A high level of phosphate can be potentially serious because it can damage your child's skin, joints and eyes.

Your child may need a medication that is known as a phosphate binder. Phosphate binders work by binding (sticking) to the phosphate in the food inside your child's stomach, stopping it from being absorbed into their body.

To work properly, phosphate binders must be taken with meals. The most commonly used phosphate binders are calcium carbonate and, less commonly, aluminium hydroxide.

The side effects of phosphate binders are uncommon but include:

  • nausea
  • stomachache
  • constipation
  • diarrhoea
  • flatulence (wind)
  • skin rash
  • itchy skin 

Many children with chronic kidney disease will have delayed growth. This is because the kidneys produce some of the hormones that are used to stimulate physical growth.

To compensate for this, your child may need human growth hormone (HGH). HGH is given by injection and it is a synthetic version of the hormones used by the body to stimulate growth.

The most common side effects of HGH are some minor reddening, plus irritation and pain at the site of the injection. These side effects should pass within a few hours.

Almost all children with ARPKD (with the exception of category 4 ARPKD) will have kidney failure at some point in their life. While kidney failure can sometimes be treated with medication in the short to medium term, the only long-term treatment options are a kidney transplant or dialysis.

See the Health A-Z topics about Chronic kidney disease - treatment, Kidney transplants and Dialysis for more information.

Liver disease

The most common difficulty faced by children with ARPKD who are affected by liver disease is that they experience bleeding from their varices (varices are new blood vessels that form due to scarring of the liver).

A treatment called sclerotherapy is often used to treat varices in children with ARPKD. In sclerotherapy, a special solution is injected into the blood vessels to help shrink the blood vessels.

Protecting your child’s kidneys

If your child has ARPKD, their kidneys will be very vulnerable to injury. A sudden knock or blow to their kidneys could cause the cysts to split and bleed, leading to severe and intense pain.

Due to this risk, it is recommended that your child avoids taking part in contact sports, such as football and rugby.

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Page last reviewed: 13/07/2011

Failure to thrive

Around a quarter to a third of children with autosomal recessive polycystic kidney disease (ARPKD) will fail to thrive after birth. The reasons for this are uncertain.

'Failure to thrive' is a medical term that means that a child does not put on weight at the expected rate. It should not be confused with a growth deficiency, which is where a child does not grow at the expected rate.

If this is the case with your child, they may need to be referred to a dietician (an expert in food and nutrition) as they may need a high calorie and protein diet to boost their weight.

Urinary tract infections (UTIs)

If your child has ARPKD, they have an increased risk of developing a urinary tract infection (UTI). A UTI is an infection that develops inside their urinary system, which is made up of:

  • the kidneys
  • the ureters - the tubes that run from the kidney to the bladder
  • the bladder - a 'balloon-shaped' organ that stores urine
  • the urethra - the tube that runs from the bladder through the penis (in males) or vulva (in females) through which urine passes

Some common symptoms of UTIs include:

  • high temperature (fever) of 38ºC (100.4ºF)  or above
  • vomiting
  • blood in the urine
  • unpleasant smelling urine
  • frequent need to urinate
  • pain when urinating

UTIs can be treated with antibiotics. Young babies under the age of three months, or children with more severe symptoms, may need to be admitted to hospital as a precaution.

Polyuria and polydipsia

Two related complications that affect children with ARPKD are:

  • polyuria - large amounts of urine are passed and there is a need to urinate frequently
  • polydipsia - an excessive and prolonged thirst

Both polyuria and polydipsia are caused by damage to parts of the kidneys called nephrons. Nephrons control how much water is reabsorbed into the body and how much is passed as urine. Many children with polyuria will experience episodes of bedwetting (enuresis).

Also, the excessive amount of urine that is passed from your child's body means that they are potentially at risk of dehydration, particularly if they have a high temperature, they are vomiting or if they have diarrhoea.

Dehydration occurs when a person has a severe lack of fluid in their body. Signs and symptoms of dehydration may include:

  • dry mouth and lips
  • sunken features (particularly the eyes)
  • headaches
  • dizziness
  • confusion and irritability

Treatment for dehydration includes oral rehydration solution (ORS). ORS usually come in sachets that are available over the counter without a prescription from your local pharmacist. You dissolve them in water and they help to replace salt, glucose and other important minerals that are lost through dehydration.

If your child vomits after drinking an ORS solution, you should wait 5-10 minutes before giving them some more. However, make sure they drink it slowly. For example, give them a spoonful every few minutes.

It is usually recommended that your child drinks an ORS each time that they pass a large amount of watery stools. However, the exact amount of ORS that they should drink will depend on their size and weight. Your pharmacist can advise you about this. The manufacturer's instructions that come with the ORS will also have information on the recommended dosage.

Abdomen
The abdomen is the part of the body between the chest and the hips.
Bile duct
The bile duct is the tube which carries bile from your liver to your gall bladder. Bile helps digest food.
Blood
Blood supplies oxygen to the body and removes carbon dioxide. It is pumped around the body by the heart.
Congenital
Congenital means a condition that is present at birth- the condition could be hereditary or develop during pregnancy.
Deformity
Deformity is used to describe a part of the body that is not the usual shape. This could develop during pregnancy or as a result of a condition or injury.
Inflammation
Inflammation is the body's response to infection, irritation or injury, which causes redness, swelling, pain and sometimes a feeling of heat in the affected area.
Kidney
Kidneys are a pair of bean-shaped organs located at the back of the abdomen, which remove waste and extra fluid from the blood and pass them out of the body as urine.
Liver
The liver is the largest organ in the body. Its main jobs are to secrete bile (to help digestion), detoxify the blood and change food into energy.
Lung
Lungs are a pair of organs in the chest that control breathing. They remove carbon dioxide from the blood and replace it with oxygen.
Platelets
Platelets are cells in the blood that control bleeding by plugging the broken blood vessel and helping the blood to clot.
Rupture
A rupture is a break or tear in an organ or tissue.
Veins

Veins are blood vessels that carry blood from the rest of the body back to the heart.

 

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