Polycystic Kidney Disease

views updated

Polycystic Kidney Disease


Polycystic kidney disease (PKD) is one of the most common of all life-threatening human genetic disorders. It is an incurable genetic disorder characterized by the formation of fluid-filled cysts in the kidneys of affected individuals. These cysts multiply over time. It was originally believed that the cysts eventually caused kidney failure by crowding out the healthy kidney tissue. It is now thought that the kidney damage seen in PKD is actually the result of the body's immune system. The immune system, in its attempts to rid the kidney of the cysts, instead progressively destroys the formerly healthy kidney tissue.


A healthy kidney is about the same size as a human fist. PKD cysts, which can be as small as the head of a pin or as large as a grapefruit, can expand the kidneys until each one is bigger than a football and weighs as much as 38lb (17 kg).

There are two types of PKD: infantile PKD, which generally shows symptoms prior to birth; and adult onset PKD. Individuals affected with infantile PKD are often stillborn. Among the liveborn individuals affected with infantile PKD, very few of these children survive to the age of two. The adult onset form of PKD is much more common. The time and degree of symptom onset in the adult form of PKD can vary widely, even within a single family with two or more affected individuals. Symptoms of this form of PKD usually start to appear between the ages of 20 and 50. Organ deterioration progresses more slowly in adult onset PKD than it does in the infantile form; but, if left untreated, adult onset PKD also eventually leads to kidney failure.

One of the most common of all life-threatening genetic diseases, PKD affects more than 60,000 Americans. Over 12.5 million people worldwide are affected with PKD. Approximately one in every 400 to 1,000 people is affected with ADPKD. Another one in 10,000 affected with ARPKD. PKD is observed in equal numbers in both males and females. PKD is also observed with equal frequency among ethnic groups.

Causes and symptoms

Polycystic kidney disease is expressed as both a recessive and a dominant trait. A recessive genetic trait will not cause disease in a child unless it it inheritied from both parents. A dominant genetic trait can be inherited from just one parent. Those people affected with autosomal dominant PKD (ADPKD) have the much more common adult onset form. Those with autosomal recessive PKD (ARPKD) have the infantile form.

There are mutations on at least three genes that cause adult onset PKD. Approximately 85% of these cases are known to arise from mutations in the PKD1 gene that has been mapped to a region on the short arm of chromosome 16 (16p13.3-p13.12). Another 10-15% of cases of adult onset PKD are thought to be caused by mutations in the PKD2 gene that has been mapped to a region on the long arm of chromosome 4 (4q21-q23). As of early 2001, it is thought that the remainder of the cases of PKD are caused by mutations in the PKD3 gene, which has not yet been mapped. This unidentified "PKD3 gene" may, in fact, be more than one gene.

Adult onset PKD is transmitted from parents to their offspring as a non-sex linked (autosomal) dominant trait. This means that if either parent carries this genetic mutation, there is a 50% chance that their child will inherit this disease. In the case of two affected parents, there is a 75% probability that their children will be affected with adult onset PKD.

Infantile PKD is caused by a non-sex linked (autosomal) recessive genetic mutation that has been mapped to a region on the short arm of chromosome 6 (6p21). Both parents must be carriers of this mutation for their children to be affected with infantile PKD. In the case of two carrier parents, the probability is 25% that their child will be affected by infantile PKD.

A baby born with infantile PKD has floppy, low-set ears, a pointed nose, a small chin, and folds of skin surrounding the eyes (epicanthal folds). Large, rigid masses can be felt on the back of both thighs (flanks), and the baby usually has trouble breathing.

In the early stages of adult onset PKD, many people show no symptoms. Generally, the first symptoms to develop are: high blood pressure (hypertension ); general fatigue; pain in the lower back or the backs of the thighs; headaches; and/or urinary tract infections accompanied by frequent urination.

As PKD becomes more advanced, the kidneys' inability to function properly becomes more pronounced. The cysts on the kidney may begin to rupture and the kidneys tend to be much larger than normal. Individuals affected with PKD have a much higher rate of kidney stones than the rest of the population at this, and later stages, of the disease. Approximately 60% of those individuals affected with PKD develop cysts in the liver, while 10% develop cysts in the pancreas.

Because the kidneys are primarily responsible for cleaning the blood, individuals affected with PKD often have problems involving the circulatory system. These include: an underproduction of red blood cells which results in an insufficient supply of oxygen to the tissues and organs (anemia); an enlarged heart (cardiac hypertrophy) probably caused by long term hypertension; and, a leakage of the valve between the left chambers (auricle and ventricle) of the heart (mitral valve prolapse ). Less common (affecting approximately 5% of PKD patients) are brain aneurysms. An aneurysm is an abnormal and localized bulging of the wall of a blood vessel. If an aneurysm within the brain leaks or bursts, it may cause a stroke or even death.

Other health problems associated with adult onset PKD include: chronic leg or back pain; frequent infections; and herniations of the groin and abdomen, including herniation of the colon (diverticular disease). A herniation, or hernia, is caused when a tissue, designed to hold the shape of an underlying tissue, becomes weakened at a particular spot. The underlying tissue pushes against this weakened area until the area is no longer able to hold back the underlying tissue and the area forms an abnormal bulge through which the underlying tissue projects. Diverticular disease is caused by a weakening of the muscles that hold the shape of the organs of the digestive tract. These muscles weaken allowing these organs, particularly one section of the colon, to form sac-like projections that can trap feces and become infected, or rupture.

In the final stages of PKD, the major symptom is kidney (renal) failure. Renal failure is indicated by an increase of nitrogen (in the form of urea) in the blood (uremia, or uremic poisoning ). Uremia is a rapidly fatal condition without treatment.


Many patients who have PKD do not have any symptoms. Their condition may not be discovered unless tests that detect it are performed for other reasons.

When symptoms of PKD are present, the diagnostic procedure begins with a family medical history and physical examination of the patient. If several family members have PKD, there is a strong likelihood that the patient has it too. If the disease is advanced, the doctor will be able to feel the patient's enlarged kidneys. Heart murmur, high blood pressure, and other signs of cardiac impairment can also be detected.

Urinalysis and a blood test called creatine clearance can indicate how effectively the kidneys are functioning. Scanning procedures using intravenous dye reveal kidney enlargement or deformity and scarring caused by cysts. Ultrasound and computed tomography scans (CT scans) can reveal kidney enlargement and the cysts that caused it. CT scans can highlight cyst-damaged areas of the kidneys. A sampling of the kidney cells (biopsy) may be performed to verify the diagnosis.


There is no way to prevent cysts from forming or becoming enlarged, or to prevent PKD from progressing to kidney failure. Treatment goals include preserving healthy kidney tissue; controlling symptoms and, preventing infection and other complications.

If adult PKD is diagnosed before symptoms become evident, urinalysis and other diagnostic tests are performed at six-week intervals to monitor the patient's health status. If results indicate the presence of infection or another PKD-related health problem, aggressive antibiotic therapy is initiated to prevent inflammation that can accelerate disease progression; iron supplements or infusion of red blood cells are used to treat anemia; and surgery may be needed to drain cysts that bleed, cause pain, have become infected, or interfere with normal kidney function.

Lowering high blood pressure can slow loss of kidney function. Blood-pressure control, which is the cornerstone of PKD treatment, is difficult to achieve. Therapy may include antihypertensive medications, diuretic medications, and/or a low-salt diet. As kidney function declines, some patients need dialysis and/or a kidney transplant.

There is no known way to prevent PKD, but certain lifestyle modifications can help control symptoms. People who have PKD should not drink heavily or smoke. They should not use aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or other prescription or over-the-counter medications that can impair kidney function. Individuals affected with PKD should eat a balanced diet, exercise regularly, and maintain a weight appropriate for their height, age, and body type. Regular medical monitoring is also recommended.


There is no known cure for PKD. Those affected with infantile PKD generally die before the age of two. In adults, untreated disease can be rapidly fatal or continue to progress slowly, even after symptoms of kidney failure appear. About half of all adults with PKD also develop kidney failure. Unless the patient undergoes dialysis or has a kidney transplant, this condition usually leads to death within four years of diagnosis.

Although medical treatment can temporarily alleviate symptoms of PKD, the expanding cysts continue to increase pressure on the kidneys. Kidney failure and uremic poisoning (accumulation of waste products the body is unable to eliminate) generally cause death about 10 years after symptoms first appear.

Medications used to fight cancer and reduce elevated cholesterol levels have slowed the advance of PKD in laboratory animals. They may soon be used to treat adults and children who have the disease. Researchers are also evaluating the potential benefits of anti-inflammatory drugs, which may prevent the scarring that destroys kidney function.



Koptides, M., and C. Deltas. "Autosomal dominant polycystic kidney disease: Molecular genetics and molecular pathogenesis." Human Genetics August 2000: 115-26.

Pei, Y., A. Paterson, K. Wang, N. He, et al. "Bilineal disease and trans-heterozygotes in autosmal dominant polycystic kidney disease." American Journal of Human Genetics February 2001: 355-63.


Polycystic Kidney Disease Foundation. 4901 Main Street, Kansas City, MO 64112-2634. (800) PKD-CURE. http://www.pkdcure.org/home.htm.


Brochert, Adam, MD. "Polycystic Kidney Disease." September 4, 2000. HealthAnswers. http://www.healthanswers.com/library/library_fset.asp.

Cooper, Joel R. "Treating Polycystic Kidney Disease. What Does the Future Hold?" Coolware, Inc. http://www.coolware.com/health/medical_reporter/kidney1.html.

Online Mendelian Inheritance in Man (OMIM). February 15, 2001. http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600595.

Polycystic Kidney Disease Access Center. http://www.nhpress.com/pkd/.


Biopsy The surgical removal and microscopic examination of living tissue for diagnostic purposes.

Cancer A disease caused by uncontrolled growth of the body's cells.

Computed tomography (CT) scan An imaging procedure that produces a three-dimensional picture of organs or structures inside the body, such as the brain.

Cyst An abnormal sac or closed cavity filled with liquid or semisolid matter.

Diuretics Medications that increase the excretion of urine.

Kidney Either of two organs in the lumbar region that filter the blood, excreting the end products of the body's metabolism in the form of urine and regulating the concentrations of hydrogen, sodium, potassium, phosphate and other ions in the body.

Magnetic resonance imaging (MRI) A technique that employs magnetic fields and radio waves to create detailed images of internal body structures and organs, including the brain.

Ultrasonogram A procedure where high-frequency sound waves that cannot be heard by human ears are bounced off internal organs and tissues. These sound waves produce a pattern of echoes, which are then used by the computer to create sonograms or pictures of areas inside the body.

Uremic poisoning Accumulation of waste products in the body.