Polycystic kidney disease is a disorder that affects the kidneys and other organs. Clusters of fluid-filled sacs, called cysts, develop in the kidneys and interfere with their ability to filter waste products from the blood. The growth of cysts causes the kidneys to become enlarged and can lead to kidney failure. Cysts may also develop in other organs, particularly the liver.

Frequent complications of polycystic kidney disease include dangerously high blood pressure (hypertension), pain in the back or sides, blood in the urine (hematuria), recurrent urinary tract infections, kidney stones, and heart valve abnormalities. Additionally, people with polycystic kidney disease have an increased risk of an abnormal bulging (an aneurysm) in a large blood vessel called the aorta or in blood vessels at the base of the brain. Aneurysms can be life-threatening if they tear or rupture.

The two major forms of polycystic kidney disease are distinguished by the usual age of onset and the pattern in which it is passed through families. The autosomal dominant form (sometimes called ADPKD) has signs and symptoms that typically begin in adulthood, although cysts in the kidney are often present from birth or childhood. Autosomal dominant polycystic kidney disease can be further divided into type 1 and type 2, depending on the genetic cause. The autosomal recessive form of polycystic kidney disease (sometimes called ARPKD) is much rarer and is often lethal early in life. The signs and symptoms of this condition are usually apparent at birth or in early infancy.

Polycystic kidney disease (PKD) is a genetic disorder that causes many fluid-filled cysts to grow in your kidneys. Unlike the usually harmless simple kidney cysts that can form in the kidneys later in life, PKD cysts can change the shape of your kidneys, including making them much larger.

PKD is a form of chronic kidney disease (CKD) that reduces kidney function and may lead to kidney failure. PKD also can cause other complications, or problems, such as high blood pressure, cysts in the liver, and problems with blood vessels in your brain and heart.

PKD is one of the most common genetic disorders. PKD affects people of all ages, races, and ethnicities worldwide. The disorder occurs equally in women and men.

PKD affects about 500,000 people in the United States. ADPKD affects 1 in every 400 to 1,000 people in the world, and ARPKD affects 1 in 20,000 children.

The two main types of PKD are

• autosomal dominant PKD (ADPKD), which is usually diagnosed in adulthood
• autosomal recessive PKD (ARPKD), which can be diagnosed in the womb or shortly after a baby is born

PKD affects people of all ages, races, and ethnicities worldwide. The disorder occurs equally in women and men.

The signs and symptoms of ADPKD, such as pain, high blood pressure, and kidney failure, are also PKD complications. In many cases, ADPKD does not cause signs or symptoms until your kidney cysts are a half inch or larger in size.

Early signs of ARPKD in the womb are larger-than-normal kidneys and a smaller-than-average size baby, a condition called growth failure. The early signs of ARPKD are also complications. However, some people with ARPKD do not develop signs or symptoms until later in childhood or even adulthood.

Mutations in the PKD1, PKD2, and PKHD1 genes cause polycystic kidney disease.

Mutations in either the PKD1 or PKD2 gene can cause autosomal dominant polycystic kidney disease; PKD1 gene mutations cause ADPKD type 1, and PKD2 gene mutations cause ADPKD type 2. These genes provide instructions for making proteins whose functions are not fully understood. Researchers believe that they are involved in transmitting chemical signals from outside the cell to the cell's nucleus. The two proteins work together to promote normal kidney development, organization, and function. Mutations in the PKD1 or PKD2 gene lead to the formation of thousands of cysts, which disrupt the normal functions of the kidneys and other organs. People with mutations in the PKD2 gene, particularly women, typically have a less severe form of the disease than people with PKD1 mutations. The signs and symptoms, including a decline in kidney function, tend to appear later in adulthood in people with a PKD2 mutation.

Mutations in the PKHD1 gene cause autosomal recessive polycystic kidney disease. This gene provides instructions for making a protein whose exact function is unknown; however, the protein likely transmits chemical signals from outside the cell to the cell nucleus. Researchers have not determined how mutations in the PKHD1 gene lead to the formation of numerous cysts characteristic of polycystic kidney disease.

Although polycystic kidney disease is usually a genetic disorder, a small percentage of cases are not caused by gene mutations. These cases are called acquired polycystic kidney disease. This form of the disorder occurs most often in people with other types of kidney disease who have been treated for several years with hemodialysis (a procedure that filters waste products from the blood).

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

Normal Function

The PKHD1 gene provides instructions for making a protein called fibrocystin (sometimes known as polyductin). This protein is present in fetal and adult kidney cells, and is also present at low levels in the liver and pancreas.

Fibrocystin 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. Based on its structure, fibrocystin may act as a receptor, interacting with molecules outside the cell and receiving signals that help the cell respond to its environment. This protein also may be involved in connecting cells together (adhesion), keeping cells apart (repulsion), and promoting the growth and division of cells (proliferation).

Fibrocystin 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 play an important role in maintaining the size and structure of these tubules; however, the function of fibrocystin in primary cilia remains unclear.

Health Conditions Related to Genetic Changes

Polycystic kidney disease

More than 270 mutations in the PKHD1 gene have been identified in people with polycystic kidney disease. These mutations cause autosomal recessive polycystic kidney disease (ARPKD), which is a severe type of the disorder that is usually evident at birth or in early infancy. PKHD1 mutations include changes in single DNA building blocks (base pairs) and insertions or deletions of a small number of base pairs in the gene. These mutations disrupt the normal structure and function of the fibrocystin protein, or lead to the production of an abnormally small, nonfunctional version of the protein. Researchers have not determined how these genetic changes lead to the formation of numerous cysts characteristic of polycystic kidney disease.

Other Names for This Gene

• FCYT
• fibrocystin
• PKHD1_HUMAN
• polycystic kidney and hepatic disease 1 (autosomal recessive)
• polyductin
• TIGM1
• tigmin

Genomic Location

Most cases of polycystic kidney disease have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the PKD1 or PKD2 gene in each cell. In about 90 percent of these cases, an affected person inherits the mutation from one affected parent. The other 10 percent of cases result from a new mutation in one of the genes and occur in people with no history of the disorder in their family.

Although one altered copy of a gene in each cell is sufficient to cause the disorder, an additional mutation in the second copy of the PKD1 or PKD2 gene may make cysts grow faster and increase the severity of the disease. The rate at which cysts enlarge and cause a loss of kidney function varies widely, and may be influenced by mutations in other genes that have not been identified.

Polycystic kidney disease also can be inherited in an autosomal recessive pattern. People with this form of the condition have two altered copies of the PKHD1 gene in each cell. The parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

The sooner you know you or your child has PKD, the sooner you can keep the condition from getting worse. Getting tested if you or your child are at risk for PKD can help you take early action.

You also can take steps to help delay or prevent kidney failure. Healthy lifestyle practices such as being active, reducing stress, and quitting smoking can help.

Make lifestyle changes

Be active for 30 minutes or more on most days. Regular physical activity can help you reduce stress, manage your weight, and control your blood pressure. If you are not active now, ask your health care provider about how much and what type of physical activity is right for you.

If you play contact sports, such as football or hockey, a health care provider should do a magnetic resonance imaging (MRI) test to see whether these sports are safe for you. Trauma to your body, especially to your back and sides, may cause kidney cysts to burst.

Lose weight. Being overweight makes your kidneys work harder. Losing weight helps protect your kidneys.

Aim for 7 to 8 hours of sleep each night. Getting enough sleep is important to your overall physical and mental health and can help you manage your blood pressure and blood glucose, or blood sugar.

Reduce stress. Long-term stress can raise your blood pressure and even lead to depression. Some of the steps you take to manage your PKD are also healthy ways to cope with stress. For example, getting enough physical activity and sleep helps reduce stress.

Quit smoking. Cigarette smoking can raise your blood pressure, making your kidney damage worse. Quitting smoking may help you meet your blood pressure goals, which is good for your kidneys and can lower your chances of having a heart attack or stroke. Quitting smoking is even more important for people with PKD who have aneurysms. An aneurysm is a bulge in the wall of a blood vessel.

Change what you eat and drink

You may need to change what you eat and drink to help control your blood pressure and protect your kidneys. People with any kind of kidney disease, including PKD, should talk with a dietitian about which foods and drinks to include in their healthy eating plan and which may be harmful. Staying hydrated by drinking the right amount of fluid may help slow PKD’s progress toward kidney failure.

Take blood pressure medicines

If lifestyle and diet changes don’t help control your blood pressure, a health care provider may prescribe one or more blood pressure medicines. Two types of blood pressure medicines, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), may slow kidney disease and delay kidney failure. The names of these medicines end in –pril or –sartan.

If you have any kind of chronic kidney disease, including polycystic kidney disease (PKD), talk with a dietitian about which foods to include in your diet and which foods might be harmful. Find a dietitian who specializes in helping people with kidney disease to help you choose the right foods and plan healthy meals.

PKD may require diet changes to help lower your blood pressure by limiting how much sodium (salt) you eat. Staying hydrated by drinking the right amount of fluid may help slow PKD’s progress toward kidney failure. Eating high-quality protein and smaller portions of protein also can help protect the kidneys. As your kidneys become more damaged, you may need to eat foods lower in phosphorus and potassium. Your health care provider will use lab tests to watch your levels of these minerals.

Researchers have not yet found a way to prevent PKD. However, you may be able to slow PKD problems caused by high blood pressure, such as kidney damage. Aim for a blood pressure goal of less than 120/80. Work with a health care team to help manage your or your child’s PKD. The health care team will probably include a general practitioner and a nephrologist, a health care provider specializing in kidney health.