Polycystic Kidney Disease

What is polycystic kidney disease?

Polycystic kidney disease is a hereditary 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 (called an aneurysm) in a large blood vessel called the aorta or in blood vessels in the brain. Aneurysms can be life-threatening if they tear or rupture.

The two major forms of polycystic kidney disease are distinguished by their patterns of inheritance. 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 childhood. Autosomal dominant polycystic kidney disease can be further divided into type 1 and type 2, depending on which gene is mutated. The autosomal recessive form of polycystic kidney disease (sometimes called ARPKD) is much rarer and is often lethal. The signs and symptoms of the condition are usually apparent at birth or in early infancy.

How common is polycystic kidney disease?

Polycystic kidney disease is one of the most common inherited disorders caused by mutations in a single gene. It affects about 500,000 people in the United States. The autosomal dominant form of the disease is much more common than the autosomal recessive form. Autosomal dominant polycystic kidney disease affects 1 in 400-1,000 people, while the autosomal recessive type is estimated to occur in 1 in 20,000-40,000 people.

What genes are related to polycystic kidney disease?

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

Mutations in the PKD1 and PKD2 genes cause autosomal dominant polycystic kidney disease. The functions of the proteins made by these genes are not fully understood, but they are involved in transmitting chemical signals from outside the cell to the cell's nucleus. Researchers believe that the two proteins work together to promote normal kidney development 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 typically have a less severe form of the disease than people with PKD1 mutations.

Mutations in the PKHD1 gene cause autosomal recessive polycystic kidney disease. Although the function of this gene is not yet known, the protein made by the gene 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 and result in the characteristic features of polycystic kidney disease.

A very small number of families with polycystic kidney disease do not have apparent mutations in any of the three known genes. An unidentified gene or genes may also be responsible for this disease.

Although polycystic kidney disease is usually a genetic disorder, a small percentage of cases are not caused by gene mutations. These nonhereditary cases are called acquired polycystic kidney disease. This form of the disorder occurs most often in people who have long-term kidney damage and in those who have been treated with hemodialysis (a procedure that filters the blood in people with kidney failure).

How do people inherit polycystic kidney disease?

Most cases of polycystic kidney disease are inherited in an autosomal dominant pattern, which means affected people may have affected siblings and relatives in successive generations (such as parents and children). In about 90 percent of these cases, an affected person inherits a mutation in the PKD1 or PKD2 gene from one affected parent. The other 10 percent of cases may result from new mutations in one of the genes. These cases occur in people with no history of the disorder in their family.

People with autosomal dominant polycystic kidney disease are born with one mutated copy of the PKD1 or PKD2 gene in each cell. Then, during their lifetime, a second mutation occurs in the other copy of the gene in kidney cells or cells in other organs, triggering cyst formation. The rate at which cysts enlarge and cause a loss of kidney function varies widely; it may be accelerated by a second mutation in PKD1 or PKD2 or by mutations in other important genes.

Polycystic kidney disease also can be inherited in an autosomal recessive pattern, which means an affected person must inherit two altered copies of the PKHD1 gene to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

What other names do people use for polycystic kidney disease?

  • PKD
  • Polycystic renal disease

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