Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of PKD. ADPKD affects 1 in every 400 to 1,000 people and is the most common kidney disorder passed down through family members. Health care providers usually diagnose ADPKD between the ages of 30 and 50, when signs and symptoms start to appear, which is why it is sometimes called “adult PKD.”

“Autosomal dominant” means you can get the PKD gene mutation, or defect, from only one parent. Researchers have found two different gene mutations that cause ADPKD. Most people with ADPKD have defects in the PKD1 gene, and 1 out of 6 or 1 out of 7 people with ADPKD have a defective PKD2 gene.

Health care providers can diagnose people with PKD1 sooner because their symptoms appear sooner. People with PKD1 also usually progress more quickly to kidney failure than people with PKD2. How quickly ADPKD progresses also differs from person to person.

Autosomal Dominant Polycystic Kidney Disease (PKD) is a genetic disorder characterized by the growth of numerous cysts in both kidneys. The progressive expansion of PKD cysts slowly replaces much of the normal mass of the kidneys, and can reduce kidney function and lead to kidney failure.

What is autosomal dominant polycystic kidney disease?

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common forms of polycystic kidney disease. It is present at birth in 1 in 400 to 1 in 1,000 babies, and it affects approximately 400,000 people in the United States. ADPKD occurs in individuals and families worldwide and in all races.

Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous cysts in both kidneys. The cysts are filled with fluid. The progressive expansion of PKD cysts slowly replaces much of the normal mass of the kidneys, and can reduce kidney function and lead to kidney failure.

When PKD causes kidneys to fail - which usually happens after many years - the patient requires dialysis or kidney transplantation. About one-half of people with the major type of PKD progress to kidney failure, also called end-stage kidney disease. PKD can also cause cysts in the liver and problems in other organs, such as the heart and blood vessels in the brain.

What are the symptoms of autosomal dominant polycystic kidney disease?

ADPKD is usually an adult-onset condition. This means that many people with ADPKD live for decades without developing symptoms of renal functional decline. People who have ADPKD have renal cysts in both kidneys and may also develop cysts in other organs such as the liver and pancreas; abnormalities of blood vessels (vascular system) such as high blood pressure (hypertension) intracranial and aortic aneurysms, heart valve defects , and abdominal wall hernias. Hypertension is the most common problem as a result of ADPKD.

About half of individuals who have ADPKD develop end-stage kidney disease by the age of 60.

How is autosomal dominant polycystic kidney disease diagnosed?

ADPKD can be diagnosed using ultrasound, CT scan or MRI studies of the kidneys. The diagnostic criteria for individuals who have a 50 percent risk of developing ADPKD include:

• At least two unilateral (cysts in one kidney) or bilateral (cysts in both kidneys) cysts in individuals who are younger than age 30.

• At least two cysts in each kidney in individuals who are between 30 and 59 years.

• At least four cysts in each kidney in individuals who are 60 years old or older.

There are two genes known to be associated with ADKPD. PKD1 is found in approximately 85 percent of individuals who have ADPKD. PKD2 is found in about 15 percent of individuals who have ADPKD.

A genetic test can detect mutations in the PKD1 and PKD2 genes, the genes that, when altered, cause autosomal dominant PKD. Although this test can detect the presence of the autosomal dominant PKD mutations before cysts develop, its usefulness is limited by two factors; it cannot predict the onset or ultimate severity of the disease and no absolute cure is available to prevent the onset of the disease. On the other hand, a young person who knows of a PKD gene mutation may be able to forestall the disease through diet and blood pressure control.

Genetic testing for PDK1 and PDK2 is also available for prenatal diagnosis and preimplantation genetic diagnosis. However this testing is not usually requested for ADPKD because it is usually an adult-onset condition.

What is the treatment for autosomal dominant polycystic kidney disease?

The treatment for ADPKD is aimed at treating the kidney and non-kidney symptoms. Blood pressure is followed regularly. High blood pressure is treated with medication.

Pain in the area of the kidneys is treated as needed with pain medications, and for chronic pain, with antidepressants. When standard methods to treat kidney pain do not work, then removing the fluid in the kidney cysts may be done.

When kidney function starts to decline, treatment is aimed at slowing down the progression to kidney failure. This involves controlling high blood pressure, restricting protein in the diet, controlling build up of acid (acidosis) and preventing elevated levels of phosphate (hyperphosphatemia).

When individuals with ADPKD develop renal failure, they need to have dialysis or a renal transplant. Studies have shown that individuals with ADPKD do better on dialysis than individuals with kidney failure from other causes.

Is autosomal dominant polycystic kidney disease inherited?

ADPKD is inherited as an autosomal dominant trait in families. The phrase 'autosomal dominant' means that if one parent has the disease, there is a 50-percent chance that the disease will pass to a child of either gender. In this form, one out of a person's two copies of the gene must be altered in order for the person to develop ADPKD. Most of the time, one parent must have the disease for a child to inherit it. Either the mother or father can pass it along, but new mutations may account for up to one-fifth of new cases.

In many cases, ADPKD doesn’t cause signs or symptoms until cysts are a half inch or larger in size. For this reason, you should meet with a health care provider if you are at risk for PKD before your symptoms start.

The most common symptoms are pain in the back and sides, between the ribs and hips, and headaches. The pain can be short term or ongoing, mild or severe.

Hematuria, or blood in the urine, may be a sign of ADPKD. If you have hematuria, see a health care provider right away.

Normal Function

The PKD1 gene provides instructions for making a protein called polycystin-1. This protein is most active in kidney cells before birth; much less of the protein is made in normal adult kidneys. Although its exact function is not well understood, polycystin-1 appears to interact with a smaller, somewhat similar protein called polycystin-2.

Polycystin-1 spans the cell membrane of kidney cells, so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. This positioning of the protein allows it to interact with other proteins, carbohydrates, and fat molecules (lipids) outside the cell and to receive signals that help the cell respond to its environment. When a molecule binds to polycystin-1 on the surface of the cell, the protein interacts with polycystin-2 to trigger a cascade of chemical reactions inside the cell. These chemical reactions instruct the cell to undergo certain changes, such as maturing to take on specialized functions. Polycystin-1 and polycystin-2 likely work together to help regulate cell growth and division (proliferation), cell movement (migration), and interactions with other cells.

Polycystin-1 is also found in cell structures called primary cilia. Primary cilia are tiny, fingerlike projections that line the small tubes where urine is formed (renal tubules). Researchers believe that primary cilia sense the movement of fluid through these tubules, which appears to help maintain the tubules' size and structure. The interaction of polycystin-1 and polycystin-2 in renal tubules promotes the normal development and function of the kidneys.

Health Conditions Related to Genetic Changes

Polycystic kidney disease

More than 250 mutations in the PKD1 gene have been identified in people with polycystic kidney disease. These mutations are responsible for about 85 percent of cases of autosomal dominant polycystic kidney disease (ADPKD), which is the most common type of this disorder. Mutations in the PKD1 gene include deletions or insertions of DNA building blocks (base pairs) and alterations of one or more base pairs. Most PKD1 mutations are predicted to produce an abnormally small, nonfunctional version of the polycystin-1 protein. Although researchers are uncertain how a lack of polycystin-1 leads to the formation of cysts, it probably disrupts the protein's signaling function within the cell and in primary cilia. As a result, cells lining the renal tubules may grow and divide abnormally, leading to the growth of numerous cysts characteristic of polycystic kidney disease.

Other Names for This Gene

• Lov-1
• PBP
• Pc-1
• PC1
• PKD1_HUMAN
• polycystic kidney disease 1 (autosomal dominant)
• polycystin-1
• TRPP1

Genomic Location

Normal Function

The PKD2 gene provides instructions for making a protein called polycystin-2. This protein is found in the kidneys before birth and in many adult tissues. Although its exact function is not well understood, polycystin-2 can be regulated by a larger, somewhat similar protein called polycystin-1.

Polycystin-2 likely functions as a channel spanning the cell membrane of kidney cells. In conjunction with polycystin-1, the channel transports positively charged atoms (ions), particularly calcium ions, into the cell. This influx of calcium ions triggers a cascade of chemical reactions inside the cell that may instruct the cell to undergo certain changes, such as maturing to take on specialized functions. Polycystin-1 and polycystin-2 likely work together to help regulate cell growth and division (proliferation), cell movement (migration), and interactions with other cells.

Polycystin-2 is also active in other parts of the cell, including cellular structures called primary cilia. Primary cilia are tiny, fingerlike projections that line the small tubes where urine is formed (renal tubules). Researchers believe that primary cilia sense the movement of fluid through these tubules, which appears to help maintain the tubules' size and structure. The interaction of polycystin-1 and polycystin-2 in renal tubules promotes the normal development and function of the kidneys.

Health Conditions Related to Genetic Changes

Polycystic kidney disease

More than 75 mutations in the PKD2 gene have been identified in people with polycystic kidney disease. These mutations are responsible for about 15 percent of all cases of autosomal dominant polycystic kidney disease (ADPKD), which is the most common type of this disorder. Mutations in the PKD2 gene include changes in single DNA building blocks (base pairs) and deletions or insertions of a small number of base pairs in the gene. Most PKD2 mutations are predicted to result in the production of an abnormally small, nonfunctional version of the polycystin-2 protein. Although researchers are uncertain how a lack of polycystin-2 leads to the formation of cysts, it likely disrupts the protein's interaction with polycystin-1 and alters signaling within the cell and in primary cilia. As a result, cells lining the renal tubules may grow and divide abnormally, leading to the growth of numerous cysts characteristic of polycystic kidney disease.

Other Names for This Gene

• APKD2
• Pc-2
• PC2
• PKD2_HUMAN
• PKD4
• polycystic kidney disease 2 (autosomal dominant)
• polycystin-2
• TRPP2

Genomic Location

Most people with ADPKD have pain, high blood pressure, and kidney failure at some point in their lives.

Pain

Pain is a common complication of ADPKD and is usually due to kidney or liver cysts. Pain also can be caused by

• kidney cyst infection
• bleeding or burst kidney cysts
• urinary tract infection
• kidney stones
• tissue stretching around the kidney due to cyst growth

High blood pressure

Almost all people with ADPKD who have kidney failure have high blood pressure. High blood pressure increases your chances of heart disease and stroke. High blood pressure can also damage your kidneys even more. Keep your blood pressure under control to help delay kidney damage.

Kidney failure

Kidney failure means your kidneys no longer work well enough to stay healthy. Untreated kidney failure can lead to coma and death. More than half of people with ADPKD progress to kidney failure by age 70.

ADPKD complications, or problems, can affect many systems in your body besides your kidneys. Researchers have not found a link between PKD and kidney cancer.

You may see some ADPKD complications right away. Other complications may not appear for many years, depending on whether you have the PKD1 or PKD2 gene. Also, ADPKD complications can vary from person to person, so you may not have all of these problems.

Vascular system problems

Abnormal heart valves. Abnormal heart valves can occur in some people with ADPKD. Abnormal heart valves can cause too little blood to flow into the aorta, the large artery that carries blood from the heart to the rest of your body. Abnormal heart valves in people with ADPKD rarely need to be replaced. However, you may need more tests if your health care provider detects a heart murmur.

Brain aneurysms. An aneurysm is a bulge in the wall of a blood vessel. Aneurysms in the brain might cause headaches that are severe or feel different from other headaches. See a health care provider even before you take over-the-counter pain medicines for severe headaches or headaches that won’t go away.

Brain aneurysms can break open and cause bleeding inside the skull. Large brain aneurysms are life threatening and need immediate medical treatment. If you have an aneurysm, stop smoking and control your blood pressure and lipids.

Digestive system problems

Liver cysts. Liver cysts, which are fluid-filled cysts on the liver, are the most common nonkidney complication of ADPKD. Liver cysts don’t usually cause symptoms in people under age 30, because liver cysts are normally small and few in number in the early stages of ADPKD. In rare cases, liver cysts can eventually reduce liver function. In the most severe cases, you may need a liver transplant.

Because the hormone estrogen may affect liver cyst growth, women are more likely to have liver cysts than men. The more pregnancies a woman with ADPKD has had, the more likely she will have liver cysts.

Pancreatic cysts. PKD can also cause cysts in your pancreas. Pancreatic cysts rarely cause pancreatitis, which is inflammation, or swelling, of the pancreas.

Diverticula. Diverticula are small pouches, or sacs, that push through weak spots in your colon wall. Diverticula can cause diverticulosis. Diverticulosis can cause changes in your bowel movement patterns or pain in your abdomen.

Urinary tract problems

Urinary tract infections (UTIs). Kidney cysts can block urine flow through the kidneys so that urine stays in your urinary tract too long. When urine stays in your urinary tract too long, bacteria in your urine can cause a bladder infection or a kidney infection. A kidney infection can cause further damage to your kidneys by causing cysts to become infected.

Kidney stones. People with ADPKD sometimes have kidney stones. Kidney stones can block urine flow and cause infection and pain.

Reproductive problems

Although most women with PKD have normal pregnancies, women with PKD who have high blood pressure and decreased kidney function are more likely to have preeclampsia, or high blood pressure during pregnancy.

With preeclampsia, the fetus gets less oxygen and fewer nutrients. Women with preeclampsia should be followed closely by their health care provider during and after pregnancy. After delivery, preeclampsia goes away.

Many men with ADPKD have cysts on their seminal vesicles, which are glands in the male reproductive system that help produce semen. Seminal vesicle cysts rarely cause infertility.

People with PKD who are considering having children may want to discuss family planning concerns with a genetics counselor.

Health care providers diagnose ADPKD using imaging tests and genetic testing. A health care provider can make a diagnosis based on these tests and your age, family history of PKD, and how many cysts you have.

The sooner a health care provider can diagnose ADPKD, the better your chances of delaying complications.

Imaging tests

A specially trained technician performs imaging tests in a health care provider’s office, an outpatient center, or a hospital. A radiologist reads the images. Adults usually don’t need anesthesia for these tests. However, a health care provider may give infants or children a sedative to help them fall asleep during the test.

Ultrasound. Ultrasound uses a device called a transducer that bounces safe, painless sound waves off your organs to create an image of their structure. An abdominal ultrasound can create images of your entire urinary tract or focus specifically on the kidneys. The images can show cysts in the kidneys.

Computed tomography (CT) scans. CT scans use a combination of x-rays and computer technology to create images of your urinary tract. For a CT scan of your urinary tract, a health care provider may give you an injection of contrast medium. Contrast medium is a dye or other substance that makes structures inside your body easier to see during imaging tests. You lie on a table that slides into a tunnel-shaped device that takes the x-rays. CT scans can show more detailed images of kidney cysts than ultrasound.

Magnetic resonance imaging (MRI). MRI machines use radio waves and magnets to produce detailed pictures of your body’s internal organs and soft tissues without using x-rays. An MRI may include an injection of contrast medium. With most MRI machines, you lie on a table that slides into a tunnel-shaped machine that may be open on each end or closed at one end. Some newer machines allow you to lie in a more open space. Health care providers use MRIs to measure kidney and cyst size and monitor kidney and cyst growth. Measuring kidney and cyst size and growth can help track the progress of PKD.

Genetic testing

Your health care provider may refer you to a geneticist if you are at risk for ADPKD. A geneticist is an expert in genes and diseases that are passed down through families. You will provide the geneticist with a blood or saliva sample, which will be tested in a special lab for the gene mutations that cause ADPKD. The genetic testing may take many days or weeks to complete.

A health care provider may also use genetic testing results to find out whether someone with a family history of PKD is likely to develop PKD in the future.

When to consider genetic counseling

If you are considering genetic testing, you and your family may want to talk with a genetics counselor as part of your health care team. Genetic counseling may be useful when you’re deciding whether to have genetic testing and again later when test results are available. Genetic counseling can help you and your family understand how test results may affect your lives.

• Radiologist
• Nephrologist - a doctor who specializes in the care of kidneys
• Dietician/nutritionist
• Genetics specialist

Although a cure doesn’t exist yet for ADPKD, treatment can help reduce your complications, which can help you live longer.

Manage pain

A health care provider needs to find the source of your pain before he or she can treat it. For example, if growing cysts are causing pain, the health care provider may first suggest over-the-counter (OTC) pain medicines such as aspirin or acetaminophen.

Always talk with a health care provider before taking any OTC medicines because some may be harmful to your kidneys. People with ADPKD have a higher risk for acute kidney injury (AKI), which is the sudden and temporary loss of kidney function. Sometimes AKI is caused by using OTC painkillers for a long time.

Depending on the size and number of cysts and whether medicine helps your pain, a health care provider may suggest surgery. Surgery to shrink cysts can help pain in your back and sides for a while. However, surgery does not slow PKD’s progress toward kidney failure.

Control your blood pressure

Controlling your blood pressure can slow the effects of ADPKD. Lifestyle changes and medicines can lower high blood pressure. Sometimes you can control blood pressure with healthy eating and regular physical activity alone.

Some health care providers will recommend blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).

Treat kidney failure

ADPKD can eventually cause your kidneys to fail. People with kidney failure must have dialysis or a kidney transplant to replace their kidney function.

The two forms of dialysis are hemodialysis and peritoneal dialysis. Hemodialysis uses a machine to circulate your blood through a filter outside the body. Peritoneal dialysis uses the lining of your abdomen to filter the blood inside the body.

A kidney transplant is surgery to place a healthy kidney from a donor into your body.

Managing PKD successfully will probably include several lifestyle changes, such as changes in your physical activity level and what you eat. Visiting with a health care team on a regular basis is an important part of your routine as you work to limit your kidney problems.

PKD is a costly disease to manage and treat, especially if health insurance doesn’t cover some or any of your costs. Financial help may be available from the Federal Government and other sources. Visit the Centers for Medicare & Medicaid Services website or talk with your health care team for more information.

Many people with PKD may find it hard, but not impossible, to get life insurance. Contact an insurance company that specializes in “impaired risk life insurance.”