Patient information: Polycystic kidney disease

POLYCYSTIC KIDNEY DISEASE OVERVIEW

Normally, the kidneys filter out excess toxic and waste substances and fluid from the blood. In people with polycystic kidney disease, the kidneys become enlarged with multiple cysts that interfere with normal kidney function. This can sometimes lead to kidney (renal) failure and the need for dialysis or kidney transplantation.

There are two major forms of polycystic kidney disease: autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease.

• Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder, occurring in approximately 1 in every 400 to 1000 people. Only about one-half of people with ADPKD will be diagnosed during the person's lifetime because the disease is often without symptoms. Autosomal dominant means that there is a 50 percent risk that an affected parent will pass the mutated gene to a child.
• Autosomal recessive polycystic kidney disease (ARPKD, also called childhood polycystic kidney disease) is typically diagnosed in infancy, although less severe forms may be diagnosed later in childhood or adolescence. The estimated incidence is 1 in 10,000 to 20,000 people. Autosomal recessive means that the mutated gene must be present in both parents; a person who has only one abnormal gene is a carrier. If both parents are carriers (each having one abnormal and one normal gene), then there is a 25 percent chance that a child will inherit an abnormal gene from each and develop the disease.

The following is a discussion of autosomal dominant polycystic kidney disease, the most common cystic kidney disease.

GENETICS OF POLYCYSTIC KIDNEY DISEASE

Approximately 85 percent of families with autosomal dominant polycystic kidney disease (ADPKD) have an abnormality on chromosome 16; these people have PKD1 disease. The remaining 15 percent have a defect that involves a gene on chromosome 4; this is called PKD2 disease. In some cases, it is not possible to detect which gene is mutated.

In approximately 25 to 40 percent of cases, ADPKD occurs in people without a family history of the disease. This represents a new genetic mutation in about 10 percent of cases. More frequently, particularly in families without PKD1, it is a disease that progresses slowly and never causes symptoms.

Cysts and kidney failure occur at an earlier age in PKD1 disease; the average age of end-stage renal disease (that is, needing dialysis or a transplant) is approximately 57 years in PKD1 disease versus 69 years in non-PKD1 disease.

CYST FORMATION

Autosomal dominant polycystic kidney disease (ADPKD) appears to cause abnormal cell growth that leads to cysts on the kidneys, but the way in which cysts form is not clear.

The basic unit of the kidney is the nephron, with each kidney containing approximately one million nephrons (figure 1 and figure 2). Each nephron consists of a glomerulus, which is a collection of very small arteries intermingled among a series of tubules. The glomeruli and tubules work together to filter waste products from the bloodstream and dispose of them in the urine.

With ADPKD, a cyst begins as an expansion in a tubule. The cyst subsequently enlarges, usually due to fluid that accumulates in the cyst. The cells making up the cysts multiply, causing the cyst to grow even larger. Cysts may also grow in the liver, pancreas, and/or spleen.

EFFECTS ON THE KIDNEY

Autosomal dominant polycystic kidney disease (ADPKD) often leads to progressive kidney (renal) failure, due in part to continued enlargement of the cysts. Other effects on the kidney can occur, and include high blood pressure, kidney infection, blood in the urine (hematuria), and kidney stones. Flank and abdominal pain due can also occur.

Kidney failure — Kidney (renal) failure severe enough to require dialysis or kidney transplantation is called end-stage renal disease (ESRD). Although ADPKD can lead to ESRD in early childhood, itd most commonly occurs in middle age or later in life. The likelihood of requiring dialysis in people with ADPKD is estimated at less than 2 percent in people under age of 40, increasing to 50 to 75 percent by age 70 to 75. Kidney failure does not occur in all patients with ADPKD. (See "Patient information: Dialysis or kidney transplantation — which is right for me?".)

Risk factors — The risk of developing chronic kidney disease (a precursor to end-stage renal disease) in ADPKD depends upon a number of risk factors. Factors that increase the risk include a younger age at diagnosis, being male, having PKD1, having frequent episodes of visible blood in the urine, high blood pressure, and larger kidney size. Having more than one risk factor further increases the risk of worsening kidney disease in both men and women.

High blood pressure — High blood pressure is a common feature of autosomal dominant polycystic kidney disease (ADPKD), occurring in 60 to 70 percent of people. It is often diagnosed early in the course of the disease, before there are any signs of kidney failure. (See "Patient information: High blood pressure in adults".)

Kidney infection — Approximately 30 to 50 percent of people with ADPKD will have one or more kidney infections during their lifetime.

The primary symptoms of a kidney infection in people with ADPKD are fever and flank pain. The infection may be of the kidney or of a cyst. Not all antibiotics work well if the infection is in the cyst. Since it is not easy to tell where the infection is, most physicians will use an oral antibiotic that can penetrate the cysts. Some people with high fevers or severe symptoms need to be treated with intravenous antibiotics. (See "Patient information: Bladder infections in adolescents and adults".)

Blood in the urine — Hematuria (blood in the urine) occurs in 35 to 50 percent of people with ADPKD and may be the first sign of the disease. With hematuria, the urine may be a pink or red color. Repeated episodes of hematuria are common. (See "Patient information: Blood in the urine (hematuria) in adults".)

Hematuria is usually caused by bleeding into a cyst due to rupture of the cyst, which can occur as a result of a urinary tract infection or strenuous activity; bleeding can cause pain in the side of the low back (called flank pain). Patients with ADPKD can also develop kidney stones, which can cause hematuria and flank pain.

Hematuria related to bleeding cysts generally stops within two to seven days. The usual treatment includes bed rest and increasing fluids until the bleeding stops. If bleeding does not stop with bed rest and increased fluids, a procedure to stop the bleeding may be required.

Kidney stones — Kidney stones occur in up to 20 percent of people with polycystic kidney disease. Kidney stones may cause pain, or sometimes they can block the flow of urine without symptoms.

Treating kidney stones that block urine flow is difficult in patients with ADPKD. The cysts make it harder to surgically remove the stone or use shock waves to break up the stone (extracorporeal shock-wave lithotripsy or ESWL). (See "Patient information: Kidney stones in adults".)

Flank and abdominal pain — People with autosomal dominant polycystic kidney disease (ADPKD) often get flank and abdominal pain that is not related to infection, bleeding into a cyst, or a kidney stone. The pain is often dull and persistent and is thought to be caused by stretching of the wall of a cyst or pressure on other organs when the kidneys and/or liver are very large. In contrast, pain that begins suddenly is more likely to be caused by bleeding into or infection of a cyst, twisting of the kidney, or a kidney stone.

No specific treatment is required in most people with dull or persistent flank and abdominal pain; pain medications such as acetaminophen are often recommended. Nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen or naproxen, are sometimes recommended, although people with polycystic kidney disease should speak to their healthcare provider about the risks and benefits of NSAIDs before using them. NSAIDs are not recommended when kidney function is reduced.

Some people have persistent pain that is severe enough to limit their daily activities. Severe pain is usually evaluated with ultrasound to see if a large cyst is present in the area of pain. If so, ultrasound can be used to guide needle drainage of the cyst. Most people have significant relief of pain after drainage. However, pain commonly recurs and surgery is sometimes required to relieve the pressure of the cysts.

COMPLICATIONS OUTSIDE OF THE KIDNEY

A variety of complications outside the kidney can occur in people with autosomal dominant polycystic kidney disease (ADPKD). These complications are thought to result from the same abnormality responsible for the formation of kidney cysts.

Cerebral aneurysm — The most serious complication of polycystic kidney disease is a cerebral or brain aneurysm (a bulging blood vessel due to weakening of the blood vessel wall). Aneurysms can rupture, causing bleeding into the brain (subarachnoid hemorrhage). If not treated quickly, this can lead to irreversible brain damage or death. Aneurysm rupture occurs most often in people with larger aneurysms and/or poorly controlled high blood pressure. The most common symptoms of subarachnoid hemorrhage is a severe headache that begins suddenly, frequently with nausea and vomiting. (See "Patient information: Hemorrhagic stroke treatment".)

Approximately 4 percent of young adults with ADPKD may have brain aneurysms, and the frequency increases with age to about 10 percent in older patients. People with a family history of cerebral aneurysm or subarachnoid hemorrhage are at the highest risk of forming an aneurysm.

Early diagnosis of cerebral aneurysm is recommended in people who are at high-risk. Screening (looking for an aneurysm) is generally performed with imaging studies, such as a CT scan or magnetic resonance angiography (MRA).

At present, routine screening is recommended only for high-risk patients, such as those with a previous rupture, a positive family history of a brain hemorrhage, warning symptoms, or a person with a high-risk occupation (eg, airline pilot), in whom a loss of consciousness would place the patient or others at extreme risk.

Screening of low-risk patients is not recommended because aneurysms are rare in this group and most aneurysms that are found have a low risk of rupture. In addition, there is a high risk of severe neurologic complications associated with corrective surgery; this means that risk of fixing the aneurysm outweighs the benefit of avoiding aneurysm rupture. Thus, most low-risk patients would not derive any benefit from finding an aneurysm, since surgery for a small aneurysm would not be recommended.

Aneurysms that are greater than 7 to 10 mm in size have a high risk of rupture (up to 2 percent per year for larger aneurysms). Cerebral aneurysms of this size and those that cause symptoms may be corrected with surgery or with a procedure that involves placing a coil within the aneurysm that reduces the risk of rupture. Smaller aneurysms that do not cause symptoms are much less likely to rupture and are not routinely corrected, except in people with a history of a bleeding aneurysm.

Liver cysts — Liver cysts occur commonly in people with autosomal dominant polycystic kidney disease (ADPKD), with approximately 30 to 40 percent of people who are younger than 30 years to greater than 80 to 90 percent of people over the age of 60 being affected.

Liver cysts are more common in people with advanced chronic kidney disease. Although the incidence of polycystic liver disease is similar in men and women, very large cysts occur almost exclusively in women, and are more common in women who have had several pregnancies.

Most people with liver cysts have no symptoms and have normal or near-normal liver function. However, some people develop pain (which may require drainage of the cyst if it is persistent and severe) and/or cyst infection (which requires antibiotic therapy and, in some cases, drainage).

Heart valve disease — Abnormalities of the heart valves are detected in 25 to 30 percent of patients with ADPKD. Most patients with heart valve disease have no symptoms and require no treatment. However, the valve disease may progress over time, and can become severe enough to require valve replacement.

Colonic diverticula — A diverticulum is an outpocketing that can form in the wall of the colon, particularly at points where blood vessels enter. Diverticulosis means that diverticula are present within the colon; diverticulitis refers to inflammation of the diverticula. People with autosomal dominant polycystic kidney disease (ADPKD) have an increased likelihood of experiencing complications from colon diverticula, especially after kidney transplantation. (See "Patient information: Diverticular disease".)

Symptoms of diverticulitis include abdominal pain (which may be similar to pain caused by kidney cysts), diarrhea, and blood in the stool. People with diverticular disease who do not have any symptoms do not require specific treatment. Treatment of diverticulitis depends upon the severity of symptoms and clinical findings.

Abdominal wall hernias — A hernia is an area of weakness in a muscle. The area may protrude if the organs behind the muscle press against the area of weakness, especially as a person increases the pressure in their abdomen (such as during a cough or while carrying a heavy package). Abdominal wall hernias are relatively frequent, affecting approximately 45 percent of people with autosomal dominant polycystic kidney disease (ADPKD).

Surgery is the best treatment for abdominal wall hernias, but not all hernias require surgical repair. Small hernias may be monitored over time.

POLYCYSTIC KIDNEY DISEASE DIAGNOSIS

It is usually easy to diagnose autosomal dominant polycystic kidney disease (ADPKD) in people who develop flank or abdominal pain and have a family history of ADPKD. An imaging study, such as an ultrasound, magnetic resonance imaging scan (MRI), or CT scan is usually recommended, and may reveal large kidneys with multiple cysts on both kidneys (figure 3). Cysts may also be seen in the liver, pancreas, and spleen.

In people without a family history, ADPKD may be more difficult to diagnose. The diagnosis of polycystic kidney disease may first be suspected based on an imaging test, such as ultrasonography, performed for some other reason. The family history may be negative because family members developed symptoms at a later age and died of other causes before ADPKD was diagnosed, or did not have symptoms.

POLYCYSTIC KIDNEY DISEASE TREATMENT

Autosomal dominant polycystic kidney disease (ADPKD) often leads to kidney failure due to continued enlargement of the cysts. Treatment therefore focuses on slowing the progression of kidney failure and treating the associated features of the disease, such as kidney infections or kidney stones and flank or abdominal pain.

High blood pressure — Treating high blood pressure can have a dual benefit in people with polycystic kidney disease because it can slow the decline in kidney function and minimize the risk that a cerebral aneurysm will rupture. People with high blood pressure are much more likely to develop kidney failure.

Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) can effectively lower blood pressure in most people with ADPKD. (See "Patient information: High blood pressure treatment in adults".)

Dietary protein restriction — There are conflicting findings on the benefit of a low protein diet in people with ADPKD. Given the limited evidence of benefit, we do not recommend restricting protein intake below 1 to 1.1 g/kg per day. In this example, a 180 pound (82 kg) man would need approximately 90 grams of protein per day.

End-stage renal disease — Patients with ADPKD who progress to end-stage renal disease require either dialysis or kidney transplantation. (See "Patient information: Dialysis or kidney transplantation — which is right for me?".)

People with ADPKD who require dialysis are usually treated with hemodialysis. People with ADPKD who have hemodialysis appear to survive longer than people with other types of end-stage renal disease.

Peritoneal dialysis, a form of dialysis that involves infusing fluid into the abdomen and then draining the fluid, is less commonly performed due to the presence of the enlarged kidneys. (See "Patient information: Hemodialysis".)

The prognosis after kidney transplantation is usually excellent.

POLYCYSTIC KIDNEY DISEASE SCREENING

Screening tests are available to relatives of a person with autosomal dominant polycystic kidney disease (ADPKD). The decision to have a screening test for PKD should be discussed with an experienced healthcare provider, and should include a full discussion of the potential risks and benefits.

Screening in children — A child of a person with ADPKD can be screened for the disease before symptoms develop. The chance of a child being affected by ADPKD when one parent is affected is one in two (50 percent chance). When both parents are affected, there is a three in four (75 percent) chance of the child being affected.

However, screening is not usually recommended during childhood, unless the child has signs or symptoms of the disease, because ultrasound screening is not reliable in children. Most people with PKD do not develop cysts until later in life. In addition, learning of the diagnosis during childhood would not change the child's medical treatment but could potentially cause the child to worry.

However, a parent who has ADPKD should ensure that their child's blood pressure is measured every year, beginning at age three. Although this is recommended for all children, it is not always done. (See "Patient information: High blood pressure in children".)

Screening for polycystic kidney disease in adults — An adult with a family history of polycystic kidney disease who has no symptoms may consider being screened for the disease. However, it is important to realize that no treatment is needed for people who have no symptoms of their disease. In addition, being diagnosed with PKD could potentially affect a person's ability to obtain life insurance.

Ultrasound — Imaging tests such as ultrasound can be used to screen for ADPKD, using the criteria described below. These criteria are very sensitive in detecting PKD1; the criteria are less sensitive for people with non-PKD1 disease, who form cysts at a later age. To be diagnosed with ADPKD:

• In patients younger than 30 years of age, at least two cysts (on one or both kidneys) must be seen with ultrasound.
• In patients aged 30 to 59, at least two cysts must be seen in each kidney with ultrasound.
• In patients over age 60, four or more cysts must be seen in each kidney with ultrasound.

A negative ultrasound or CT scan does not mean that a person does not have PKD1 unless the person is older than 30 years. It is not clear when PKD2 can be excluded with ultrasound.

As an example, a person who is older than 30 years and has a negative ultrasound may eventually develop non-PKD1 disease. However, people with non-PKD1 disease have a lower risk of kidney failure compared to people with PKD1 disease. This news may be reassuring to some people.

Genetic testing — Genetic tests can also be done to screen for PKD1 or PKD2 mutations, although the use of genetic tests is limited by their cost and the test's inability to make a diagnosis in 30 percent of cases. Genetic tests may be used for:

• A young adult with a family history of ADPKD and a negative ultrasound who is a potential kidney donor
• A person whose ADPKD diagnosis is not certain based upon imaging tests

Cyst formation in ADPKD appears to begin in the fetus. However, the disease does not usually cause symptoms in young children. Genetic testing can be done during pregnancy to determine if the baby is affected, although it is not recommended for several important reasons:

• The test is not perfect and may falsely identify the baby as having ADPKD when it does not
• The test may fail to identify ADPKD when it is present
• Some people with gene mutations will never develop symptoms of ADPKD
• ADPKD does not cause symptoms until middle age in most people (by which time there may be effective therapy to prevent cyst growth).

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Dialysis or kidney transplantation — which is right for me?
Patient information: High blood pressure in adults
Patient information: Bladder infections in adolescents and adults
Patient information: Blood in the urine (hematuria) in adults
Patient information: Kidney stones in adults
Patient information: Hemorrhagic stroke treatment
Patient information: Diverticular disease
Patient information: High blood pressure treatment in adults
Patient information: Hemodialysis
Patient information: High blood pressure in children

Professional Level Information:
Course and treatment of autosomal dominant polycystic kidney disease
Diagnosis of and screening for autosomal dominant polycystic kidney disease
Extrarenal manifestations of autosomal dominant polycystic kidney disease
Genetics of autosomal dominant polycystic kidney disease and mechanisms of cyst growth
Hypertension in autosomal dominant polycystic kidney disease
Prenatal sonographic diagnosis of cystic renal disease
Renal manifestations of autosomal dominant polycystic kidney disease
Screening for intracranial aneurysm
Urinary tract infection in autosomal dominant polycystic kidney disease

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• National Institute of Diabetes and Digestive and Kidney Diseases

      (www.niddk.nih.gov)

• PKD Foundation

      (www.pkdcure.org)

• National Kidney Foundation

      (www.kidney.org)

• American Kidney Fund

      (www.akfinc.org)

• American Association of Kidney Patients

      (www.aakp.org)

[1-4]