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Patient information: Polycystic kidney disease
Burton D Rose, MD
Harvard Medical School
William M Bennett, MD
Editor Cystic Diseases

Normal kidneys filter out excess toxic and waste substances and fluid from the blood. In polycystic kidney disease, the kidneys become enlarged with multiple cysts that interfere with normal kidney function. This can lead to kidney (renal) failure.

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

The following is a discussion of autosomal dominant polycystic kidney disease.

GENETICS ? Approximately 85 percent of families with ADPKD have an abnormality on chromosome 16 (these people have what is called PKD1 disease). Most of the remaining patients have a different defect that involves a gene on chromosome 4 (called PKD2 disease); very rare families appear to have defects at different sites.

Cysts occur at a later age in non-PKD1 disease, as does end-stage renal disease (the mean age for end-stage renal disease is approximately 57 years in PKD1 disease versus 69 years in non-PKD1 disease).

In approximately 25 to 40 percent of cases, PKD occurs in people without a family history of the disease. This can represent a new mutation or, more often, particularly in non-PKD1 families, such slow progression that affected family members die from other causes before there are any manifestations of PKD.

CYST FORMATION ? The underlying mechanism by which cysts form remains unclear. It may be that the primary defect in ADPKD is abnormal cellular differentiation and maturation.

The basic unit of the kidney is the nephron, with each kidney in humans containing approximately one million nephrons. 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 pass waste products from the bloodstream to the urine.

With ADPKD, a cyst begins as an expansion in a tubule. The cysts subsequently enlarge, usually due to the secretion of fluid into the cyst. The cells making up the cysts also multiply, making the cyst even larger; it is thought that something in the cyst fluid promotes the growth of these cells. Cysts may also grow in the liver, pancreas, and spleen (see below).

KIDNEY MANIFESTATIONS ? ADPKD often leads to progressive kidney (renal) failure due in part to continued enlargement of the cysts. Other renal manifestations that can occur include high blood pressure (hypertension), kidney infection, blood in the urine (hematuria), and kidney stones (nephrolithiasis). Flank and abdominal pain due to kidney involvement is also observed.

Renal failure ? Although ADPKD can lead to end-stage renal failure in early childhood, progression most commonly occurs in middle age and later. The likelihood of requiring dialysis is estimated at less than 2 percent below the age of 40, 20 to 25 percent by age 50, 35 to 45 percent by age 60, and 50 to 75 percent by age 70 to 75. Thus, end-stage renal disease is not inevitable among all patients with ADPKD.

Risk factors ? A number of risk factors have been identified for progressive renal disease in ADPKD. These include younger age at diagnosis, black race, male gender, the type of genetic abnormality (PKD1 versus PKD2), episodes of gross hematuria, hypertension, and increased kidney size.

Hypertension ? Hypertension is a common early finding in ADPKD, occurring in 50 to 70 percent of cases. Hypertension is often diagnosed early in the course of the disease, before any significant reduction in kidney function is observed.

Kidney infection ? Approximately 30 to 50 percent of patients with ADPKD will have one or more renal infections during their lifetime. The primary manifestations of renal infection in PKD are fever and flank pain. These infections may be due either to infection of the kidney or of a cyst, and distinguishing between them is often difficult. Similar findings are also observed with bleeding into a cyst.

Hematuria ? Hematuria (blood in the urine) occurs in 35 to 50 percent of patients and may be the presenting symptom of the disease. An underlying cause of the hematuria, such as a urinary tract infection or strenuous activity, can often be identified and recurrent episodes are not uncommon.

Kidney stones ? Kidney stones occur in up to 20 percent of patients with ADPKD.

Flank and abdominal pain ? Flank and abdominal pain is a common problem in ADPKD. The pain is often dull and persistent and is thought to most frequently reflect stretching of the wall of a cyst. Acute pain can also result from bleeding into or infection of a cyst, twisting of the kidney, or an obstructing stone.

COMPLICATIONS OUTSIDE OF THE KIDNEY ? A variety of complications outside the kidney occur in ADPKD. They are thought to result from the same abnormality responsible for the formation of kidney cysts.

Cerebral aneurysm ? A cerebral aneurysm (outpouching of a blood vessel in the brain) can rupture, resulting in a brain hemorrhage, which is the most serious complication of polycystic kidney disease. Studies suggest that the incidence of aneurysms in ADPKD is approximately 4 percent in young adults, increasing with age, to as high as 10 percent in older patients. Patients with a family history of intracranial aneurysm or subarachnoid hemorrhage appear to be at greatest risk of aneurysm formation. Aneurysm rupture most often occurs in patients with larger aneurysms and/or poorly controlled hypertension.

Liver cysts ? The incidence of liver (hepatic) cysts in ADPKD increases with age, from approximately 10 percent below the age of 30 to greater than 40 percent over the age of 60. Liver cysts are more commonly seen in those with advanced renal disease. Although the incidence of polycystic liver disease is similar in men and women, massive cysts occur almost exclusively in women, and are more common in those who have had several pregnancies.

Heart valve disease ? Abnormalities of the heart valves, usually lesions that result in leakage through the valve, are detected by cardiac ultrasound in 25 to 30 percent of patients with ADPKD. Most affected patients are asymptomatic.

Colonic diverticula ? A diverticulum is a sac-like protrusion that sometimes forms in the muscular wall of the colon, particularly at points where blood vessels enter the colon. Diverticulosis means that diverticula are present within the colon; diverticulitis refers to inflammation of the diverticula.

Symptoms of this condition include abdominal pain (that may be difficult to distinguish from the pain induced by the renal cysts), diarrhea, and blood in the stool. The incidence of diverticular disease appears to be higher in patients with ADPKD than in those without the disease.

Abdominal wall hernias ? Abdominal wall hernias occur in 45 percent of patients with ADPKD; a much higher percentage than in patients with other causes of chronic renal failure or in those undergoing general surgery.

DIAGNOSIS ? The diagnosis of ADPKD is easy to establish in people with a positive family history of PKD and flank or abdominal pain. Imaging studies, such as ultrasonography, IVP (intravenous pyelogram), or CT scanning, will reveal large kidneys with multiple cysts on both kidneys. Cysts may also be seen in the liver, pancreas, and spleen.

In some cases, the diagnosis of ADPKD is first suspected from an imaging test, such as ultrasonography, which was performed for the evaluation of otherwise unexplained renal failure or hematuria. This occurs most frequently in the 25 to 40 percent of new cases who have a negative family history. As noted above, the family history is usually negative because family members develop renal failure at a later age, in which case affected patients die of other causes before the diagnosis is made. In this setting, in which the diagnosis may be difficult to establish by ultrasonography of the patient alone, examining the patient's parents may reveal multiple renal cysts in one parent.

TREATMENT ? ADPKD often leads to progressive renal failure due in part to continued enlargement of the cysts. Treatment therefore focuses on retarding the progression of renal failure and treating the associated features of the disease, such as kidney infections or stones and flank or abdominal pain.

Treatment of renal dysfunction

Antihypertensive therapy ? Effective treatment of hypertension may have a dual benefit in patients with ADPKD, by both slowing the rate of decline in renal function and by minimizing the risk of rupture of a cerebral aneurysm. Patients with hypertension are much more likely to develop progressive renal failure. However, it is not clear whether the renal disease causes the hypertension or the development of hypertension exacerbates the renal injury. Angiotensin converting enzyme (ACE) inhibitors can effectively lower blood pressure in most patients with ADPKD.

Dietary protein restriction ? There are conflicting findings on the efficacy of a low protein diet. At present, given the limited evidence of benefit, we do not recommend a restriction of protein intake below 1 to 1.1 g/kg per day in patients with ADPKD.

End-stage renal disease ? Patients with ADPKD who progress to end-stage renal disease require renal replacement therapy, through either dialysis or kidney transplantation.

Patients with ADPKD who require dialysis are usually treated with hemodialysis. Survival of patients with ADPKD undergoing hemodialysis appears to be superior to that of patients with other causes of end-stage renal disease. Peritoneal dialysis, a form of dialysis that uses the peritoneal membrane in the abdomen to filter waste products in place of the kidneys, is less commonly performed, because of the presence of enlarged kidneys.

The outcomes with renal transplantation are usually excellent. However, there are some issues in the renal transplant recipient that are specific for ADPKD. Some patients, for example, require their native kidneys to be removed to better accommodate the transplanted kidney.

Treatment of other manifestations

Hematuria ? Hematuria generally resolves within two to seven days. Good hydration should be maintained with bed rest until the bleeding stops. If bleeding is persistent, radiographic procedures are usually necessary to stop it.

Kidney infections ? The majority of patients with kidney infections respond to the administration of appropriate antibiotics.

Kidney stones ? Treating obstructing kidney stones is more difficult in patients with ADPKD than in patients with stone disease that occurs by itself. 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).

Flank and abdominal pain ? No specific therapy other than nonnarcotic analgesics, such as short term administration of acetaminophen , is required in the great majority of patients with flank and abdominal pain. However, some patients have persistent pain that is severe enough to diminish the quality of life or to require narcotics for pain control. In this setting, ultrasonography should be performed to see if a large cyst is present in the area of pain. If so, ultrasound can be used to guide a needle to the cyst so it can be drained. Most patients experience substantial pain relief after this minimally invasive procedure. However, pain recurrence is common and surgery is sometimes required to relieve the pressure of the cysts.

Cerebral aneurysm ? Early diagnosis of cerebral aneurysm is important in patients at risk. 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, a high-risk occupation (eg, airline pilot) in which loss of consciousness would place the patient or others at extreme risk, and prior to surgery that is likely to be associated with the unstable blood circulation. Screening is generally performed with imaging studies, such as a CT scan or magnetic resonance angiography. Screening of low-risk patients is not recommended because the risk of corrective surgery may exceed the benefit.

Cerebral aneurysms associated with symptoms or those 10 mm in diameter should be corrected surgically, since these lesions have a high risk of rupture (up to 2 percent per year for larger aneurysms). Smaller, asymptomatic aneurysms are much less likely to rupture and are not routinely corrected, except in patients with a previous bleed.

Liver cysts ? Most patients with liver cysts remain without symptoms and have preserved liver function. However, some patients develop pain (which may require decompression of the cyst if it is persistent and severe) and/or cyst infection (which requires antibiotic therapy and, in some cases, drainage).

Heart valve involvement ? Most patients with valvular involvement are asymptomatic and require no treatment. However, the valve disease may progress over time, and can become severe enough to require valve replacement. Some patients need to take antibiotics before undergoing dental or surgical procedures to prevent infection of the heart valves.

Colonic diverticula ? Patients 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 ? Surgery is the definitive treatment for abdominal wall hernias, but not all hernias require surgical repair.

SCREENING ? Since ADPKD is an inherited disease, children of a person who has ADPKD can be screened for the disease before signs or symptoms occur, both for genetic counseling and possible early therapy. Cyst formation in ADPKD appears to begin in the fetus. However, the onset of clinical disease is relatively uncommon in young children, and screening is more often performed in persons over the age of 20.

Imaging tests can be used to screen for ADPKD. In a person with PKD1 disease, a positive test with ultrasonography requires:

The presence of non-kidney manifestations and/or enlarged kidneys can help to establish the diagnosis of ADPKD in problem cases.

In those with PKD1 disease, the probability of a positive ultrasonogram is estimated to be 8 percent in patients younger than age 10 and increases to almost 100 percent by the age of 30. Thus, a negative ultrasound cannot definitely exclude the disease until the patient is over 30 to 35 years of age. If CT scanning is used, the age at which a negative test (no cysts in either the kidneys or the liver) virtually excludes the presence of PKD is about 20 to 25, because the CT scanner can detect smaller cysts than an ultrasound.

The above statistics do not apply to patients with non-PKD1 disease, who form cysts at a later age. Thus, a negative ultrasound above the age of 30 may not exclude the eventual development of polycystic kidney disease, but it is associated with a very low risk for renal failure later in life.

Genetic tests can also be done to screen for PKD1 disease, but they are not widely available. As a general rule, genetic tests are only used for the young adult with a family history of ADPKD and a negative ultrasonogram who is a potential renal transplant donor, or to assess the genetic makeup of a fetus at-risk for ADPKD if the pregnancy outcome would be affected by the result.

As noted above, high-risk patients with ADPKD may be screened for the presence of a cerebral aneurysm, since a ruptured aneurysm can lead to irreversible neurologic damage or death.

WHERE TO GET MORE INFORMATION ? Your doctor is the best resource for finding out important information related to your particular case. Not all patients with kidney disease are alike, and it is important that your situation is evaluated by someone who knows you as a whole person.

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