POLYCYSTIC KIDNEY DISEASE (PKD)
PKD is a genetic disorder characterized by the growth of numerous fluid filled cysts in the kidneys.
It is the most common of all life-threatening genetic diseases, affecting over 600,000 Americans and over 13 million children and adults worldwide. More people have PKD than the combined number of people who have cystic fibrosis, muscular dystrophy, hemophilia, sickle cell anemia, down’s syndrome and Huntington’s disease.
In the final stages of this disease, PKD cysts slowly replace much of the mass of the kidneys, reducing kidney function and leading to kidney failure.
There are two types of PKD:
AUTOSOMAL DOMINANT (ADPKD)
The most common form of PKD. In ADPKD, one parent has the disease. There is a 50% chance that the disease will pass to a child. Either the mother or the father can pass it along. Many people with ADPKD live for decades without developing symptoms. For this reason, ADPKD is often called “adult onset polycystic kidney disease”. But that name can be confusing, since ADPKD is caused by an abnormal gene that has been present since the person was conceived. Cysts may form at any time in a person’s life.
AUTOSOMAL RECESSIVE (ARPKD)
A rare form of PKD affecting about 10% of all PKD patients. Parents who do not have the disease can have a child with the disease if both parents carry the abnormal gene. The chance of both parents passing along the abnormal gene to their baby is one in four. If only one parent carries the abnormal gene, the baby cannot get the disease. The symptoms of ARPKD can begin in the womb, so it is often called “infantile PKD”. Children born with ARPKD usually develop kidney failure within a few years after birth. Babies with the worst cases die hours or days after birth – other children may have sufficient renal function for a few years. Because kidney function is important to early physical development, children with ARPKD are usually smaller in stature. ARPKD patients may live into their teens and twenties and usually will have liver problems as well. As with ADPKD patients, the only treatment in response to kidney failure is dialysis or transplantation.
How come I’ve never heard of this disease? Is it a new disease?
In the 1700s and 1800s, PKD was often given the label of Bright’s disease. This term encompassed any of several kidney diseases marked by high concentrations of protein in the urine. Today, we know that many of the cases of Bright’s disease were actually cases of PKD. The first documented case of PKD dates back to Stefan Bathory, the King of Poland, who lived from 1533 to 1588.
In addition, the PKD Foundation is the only organization in the world that focuses on PKD and it was not formed until the mid-1980s. It wasn’t until fairly recently that PKD has gained some momentum in raising awareness and funds for the disease.
Another reason many have not heard of PKD is because it is an “internal disorder” — meaning that it does not have a dramatic affect on a person’s outward appearance. A person living with PKD may have pain or trauma on their internal organs, yet they maintain a very “normal” physical appearance that does not attract attention or compassion from the unknowing public.*
*source: National PKD Foundation
What are Cysts?
A cyst in the kidney begins as an out-pouching of the nephron, similar to a blister. Cysts can occur anywhere on the length of the nephron. Although polycystic means many cysts, not every nephron forms cysts. The fluid inside the cysts often reflects the area in the nephron from which the cyst arose.
Approximately 70 percent of cysts detach from the nephron when they are still very small, about 2 mm (1/8 inch) in diameter. Over time the cysts enlarge and can become filled with clear fluid or fluid that contains blood or white blood cells.
Cysts can form in other organs as well as the kidney; the most common other site is the liver. Current research suggests that liver cysts are associated with the bile ducts or tubules of the liver rather than liver cells themselves. It appears that rather than take the place of functioning liver cells, cysts merely push the liver cells aside. This is why liver cysts don’t cause liver failure even though the liver can become quite enlarged due to cysts.
Research has shown that there are at least three components to cyst formation:
Cell proliferation: The cells of a cyst wall reproduce themselves more than do normal kidney cells. This makes the cysts grow in size.
Cellular secretion: Secretion is a way of making fluid. To form a cyst the cells themselves must produce fluid. If there were no fluid produced to fill the cyst, there would merely be a ball of cells.
Abnormal basement membrane: The basement membrane is a very thin layer of tissue the cyst cells sit on. In ADPKD this layer is thicker than usual and is made up incorrectly.
In general, cysts cause problems because of their size and the space they occupy. The size of the kidneys and liver is directly related to how many and how big the cysts are. For example, people with kidneys over 15 cm (6 inches) are more likely to have pain than people with smaller kidneys.
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Inheritance of PKD
Because PKD is an inherited disorder, the dominant form of the disease (ADPKD) is passed from one generation to the next by an affected parent. Each child of an ADPKD parent has a 50 percent chance of inheriting the disease. Scientists have also discovered that approximately 10% of the PKD patient community became affected through spontaneous mutation, and not through inheritance. ADPKD equally affects men and women, regardless of age, race, or ethnic origin.
Each cell nucleus contains tiny threads called chromosomes. All the necessary information that is required to direct the formation and function of a human being is contained in these chromosomes. The chromosomes in turn are composed of genes, which are the basic units of heredity. Genes are so small that they remain invisible even under an electron microscope. Genes, therefore, are studied by molecular geneticists.
The goal in ultimately curing a genetically inherited disease is to find out what the abnormal protein is and try to fix it. An amazing thing we know is that there is more than one gene that causes ADPKD. There appears to be at least three genes that can cause ADPKD. About 80 percent of the people with ADPKD have the ADPKD1 gene, located on chromosome 16. Most of the rest of the ADPKD population has the ADPKD2 gene located on chromosome 4. The location of the ADPKD3 gene has not as yet been determined.
It appears that the disease caused by the ADPKD1 and ADPKD2 genes are somewhat different. With the ADPKD1 gene, cysts seem to form at an earlier age, there appears to be an earlier onset of high blood pressure and earlier loss of kidney function as compared to the ADPKD2 gene.
The risk of having a child who inherits the chromosome with the affected gene is always 50 percent with each pregnancy no matter how many children a person has. In some families, all of the children are affected; in other families, none are. Many families with multiple children will have both affected and unaffected children.
PKD does not skip a generation. However, symptoms and progression of the disease do not necessarily affect each generation in the same way.
The gene for ADPKD is dominant, which means there only has to be one copy of the gene passed on from either an affected mother or father to cause the disease. There is no carrier state with a dominant gene; it does not hide and come out in a later generation. So if a person has the gene, at some time in his/her life at least some of the manifestations of the disease will occur. When an individual does not have the gene for ADPKD, he/she does not have the disease and therefore cannot pass the gene on to the next generation.
In ADPKD there is also approximately a 10 percent rate of spontaneous mutation. This means that instead of inheriting the ADPKD gene from a parent with the disease, the gene mutates by itself for no known reason. It is important to know that even with a true spontaneous mutation, a newly affected person will still pass the mutated gene on to his/her children.
Everyone who has ADPKD in the same family has the same type of ADPKD gene and the same defect in that gene. However, even in the same family, signs and symptoms and the course of the disease are very often different. It is very difficult to predict the course of the disease in any one family member by looking at the progression of the disease in his/her parent or siblings.
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Signs, Symptoms and Diagnosis
Early in the disease there generally are no symptoms at all. In most cases of ADPKD, the person’s physical condition appears normal for many years, even decades, so the disease is often undetected. Often the first sign of ADPKD is high blood pressure, blood in the urine or a feeling of heaviness/pain in the back, sides or abdomen. Sometimes the first sign is urinary tract infection and/or kidney stones.
On the average, patients start to notice these symptoms between the ages of 20 and 40.
As the disease advances, the disease affects the kidneys as well as other organs. The degree and time of onset of the symptoms of PKD can vary greatly from one family to another, and even within families. This makes it difficult to determine beforehand what an individual’s PKD experience will be like.
High blood pressure, or hypertension, affects about 60 percent to 70 percent of people with ADPKD. High blood pressure begins early in the course of ADPKD. In ADPKD it seems that the most likely reason for high blood pressure is the constricting of blood vessels. In ADPKD, cysts can press on blood vessels in the kidney, resulting in decreased blood flow to some parts of the kidney. Sensors in the nephron react as though the blood pressure in the kidney was low; renin is then secreted, which in turn generates angiotensin, constricting the blood vessels, and causing high blood pressure. If not treated, hypertension damages the kidneys, enlarges the heart and can cause strokes.
Chronic pain is one of the most common problems for people with ADPKD. The pain is usually in the back or the side and occasionally in the stomach. The pain can be intermittent and mild requiring only occasional mild pain medicine such as acetaminophen. In a small number of people, the pain can be constant and quite severe.
Close to 50 percent of those with ADPKD have had or will have blood in their urine at some time. This is called hematuria. The urine may look pink, red or brown. Passing small amounts of red blood cells in the urine that can only be seen under a microscope may also occur. This is called microscopic hematuria. Blood in the urine can last for a day or less or the bleeding may go on for days. Strict bed rest, increased fluid intake, and acetaminophen (if there is pain) are usually the treatments if the bleeding is prolonged.
Urinary tract infection, commonly called UTI, is an infection caused by bacteria that have reached the bladder, kidneys or the cysts themselves. The infection usually starts in the bladder and can progress up the ureters into the kidneys. Although both men and women have UTIs, they are far more common in women. UTIs are quite common in the general population, but they appear to be more frequent in those with ADPKD. The most common symptom of UTI is pain or burning with urination and/or an urgent need to urinate even though there is only a small amount of urine. When the infection is in the kidney or in a cyst, there may be a sudden onset of fever, chills and back or flank pain.
Kidney stones occur in about 20 percent to 30 percent of people with ADPKD compared to 8 percent to 10 percent in the general population. One reason kidney stones are more common may be due to cysts blocking the tubules, preventing normal drainage. When the urine stays in one area longer than it should, crystals can form and cause kidney stones. Another reason that stones may form in some people with ADPKD is that there is a decrease in urine citrate. Urine citrate is a substance that prevents formation of kidney stones. The symptoms of kidney stones are severe pain in the back, side or into the groin. Often there will be blood in the urine when passing a kidney stone.
Although everyone with the ADPKD gene develops kidney cysts, not everyone progresses to kidney failure, and if they do it’s rarely before the age of 40.
A physician is alerted to the possibility of ADPKD in three different settings: when someone reports that there is a family history of ADPKD, when there are signs and symptoms that commonly occur in ADPKD, or when a test is done for some other reason and cysts are found in the kidney.
Currently, there are three main clinical tests that can be used to diagnose a person with PKD: ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI).
Ultrasound is the best screening for ADPKD. Although the majority of ADPKD patients have cysts by the time they are adults, it is only after the age of 30 that a negative ultrasound probably means that someone has less than a 5 percent chance of having ADPKD. Also, ADPKD1 appears to have a more aggressive course than ADPKD2 … therefore, unless it is clear that your family has ADPKD1, the disease may not be detectable by ultrasound until even later in life.
The reason computed tomography (CT) scans are not used as the first test to diagnose ADPKD is that CT uses radiation and often requires dye. CT scan is the best test when certain complications like bleeding into a cyst or kidney stones are suspected. The limitations of both ultrasonography and CT scan is that the cysts have to be large enough to be seen.
For now, gene linkage study is the most accurate test when the cysts cannot be seen by ultrasonography or CT scan. Gene linkage can determine ADPKD status with a 99 percent probability in informative families. However, gene linkage is quite expensive ($2,200/family) and requires several other family members with ADPKD to donate blood samples. Because of this, gene linkage is usually used only when an undiagnosed family member would like to donate a kidney to another family member or when the outcome of a pregnancy would be altered if a positive diagnosis were made in the fetus.
What are complications of PKD?
ADPKD is not just a kidney disorder; other organs can be affected, including the liver, heart and intestines.
In the Kidneys:
Both kidneys develop numerous and often large cysts. These cysts may get infected or rupture, causing severe chronic or intermittent pain.
Kidneys that would be the size of a fist normally may become substantially larger. In fully developed PKD, a cyst filled kidney can be as large as a football and make the body appear pregnant.
Kidney stones are more prevalent than in the general public.
Kidney function deteriorates substantially.
Women who have had multiple pregnancies – particularly 3 or more, are at an increased risk for acceleration of cyst growth.
In the Liver:
Cysts will develop in about 60% of PKD patients. Rarely occur in those under age 30 but do form and increase as a person ages.
Almost never fails because of cysts from PKD, even though there is an increase in liver size.
In a few patients, liver cysts can cause chronic pain due to the size and location of the cysts.
Women typically have liver cysts earlier and have more and larger cysts then men. Women who have been pregnant are more likely to have liver cysts; and the cysts are more numerous and larger in women who have been pregnant.
In the Brain:
Intracranial aneurysms in the brain occur in about 5 – 10% of PKD patients. Patients with a family member who has an aneurysm or has ruptured an aneurysm are at a higher risk of having an aneurysm also. Intracranial aneurysms are outpouching of blood vessels in the brain.
Aneurysms that leak blood or burst are extremely serious. Symptoms include sudden severe headache, pain in moving the neck, nausea and vomiting.
In the Pancreas:
Cysts will develop in about 10% of PKD patients.
Almost never fails because of cysts from PKD.
In the Heart:
Mitro valves weaken or have abnormalities in about 25% of PKD patients – as compared to 2-3% of the general population. . Mitral valve prolapse is a condition where the valve separating the top and the bottom of the left side of the heart does not close properly. This can cause blood to leak back to the top part of the heart.
An enlarged heart is common in older inviduals – may be caused from long term hypertension.
TREATMENT OPTIONS / KIDNEY FAILURE
• NUTRITION AND DIETARY MODIFICATIONS
• PAIN MANAGEMENT
• THE CHANCES OF KIDNEY FAILURE
Nutrition and Dietary Modification of ADPKD
Current research demonstrates that a person with ADPKD can play a major role in controlling the development of their disease with regular health care maintenance, a good diet and regular exercise.
At this time there is no specific diet that will make polycystic kidneys better or keep them from getting worse. However, one of the functions of the kidney is to remove waste products from the body. The major source of these waste products is the food we eat, especially protein. When a person has lost a significant amount of kidney function, a low protein diet may be ordered by his/her physician.
Avoiding large amounts of red meat can help protect your kidneys. It is probably a good idea to eat a hamburger or small steak only a couple of times a week and to include other good sources of protein in your diet, such as chicken, fish, beans and pasta.
Excessive amounts of salt should be avoided. This becomes important when people are on certain types of blood pressure medicine and when they have kidney failure. Dietary salt intake can cause unnecessary increases in blood pressure. The problem with salt is that most people like its taste and most foods have salt added to them. Salt is a preservative, so any canned food, pre-prepared food, bottled sodas or food from fast-food chains are loaded with salt. Fresh fruits, salads and most fresh vegetables are healthy alternatives and their preparation is not that time-consuming.
Drinking lots of water is very helpful. When people drink lots of liquids, their kidneys make more urine. This allows the body to flush out waste products more easily. It is also important to drink lots of water to avoid dehydration. In ADPKD, the kidneys can have trouble holding onto water. Therefore, it is important to bring lots of water or other liquids with you on long hikes, bike trips or camping trips.
It is suggested that patients with polycystic kidneys and polycystic livers refrain from caffeinated beverages such as coffee, tea and certain cold drinks. Recent experimental evidence in laboratory models of PKD indicate that the caffeine may conceivably cause kidney and liver cysts to expand at a faster rate than usual. Caffeine is known to increase within kidney cells the level of a compound called cyclic AMP that causes increased rates of cyst enlargement. There are no clinical studies, however, that prove or disprove that caffeine affects the rate that kidney cysts expand. Nonetheless, it seems appropriate to alert patients to the possibility that caffeine could potentially have harmful effects on polycystic kidneys.
Light and/or occasional use of alcohol has not been shown to damage kidneys or the liver. However, drinking three or more ounces of alcohol a day has been associated with increases in blood pressure and can damage the liver.
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Pain Management of ADPKD
Pain in the back and sides between the ribs and the hips are frequent complaints of PKD patients. Doctors will first suggest over the counter pain medications, such as Tylenol. Studies have shown that non-steroidal anti-inflammatory medications (aspirin, ibuprofen, naproxy with trade names such as Advil, Nuprin and Motril) can reduce the flow of blood through the kidneys and aggravate high blood pressure of PKD patients and therefore should be avoided. Tylenol (or other acetaminophen agents) can be used in small doses for short periods of time but patients with severe long term pain may have to work with a chronic pain management specialist.
Laparoscopic surgery to “unroof” cysts (also called de-roofing) has been used to reduce pain in ADPKD patient with severe chronic pain. Laparoscopic surgery is similar to arthroscopic surgery in that only a very small incision is necessary for the procedure, and the surgical recovery time and scarring are much reduced. This procedure is conducted only in patients whose symptoms strongly suggest that their pain is caused by the cysts, and who have cysts larger than five millimeters in diameter. This procedure is only to reduce pain, not to preserve kidney function. There are risks associated with this procedure, and the result is not permanent as studies have shown that cysts will grow back.
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What are the chances that a PKD patient can develop kidney failure?
More than 60 percent of the individuals with PKD develop kidney failure, or end-stage renal disease (ESRD), for which dialysis and transplantation are reasonable treatments. However, there is currently no known treatment or cure for PKD.
The progression to end-stage renal failure is usually gradual for people with ADPKD. End-stage renal disease is a condition where the kidneys can no longer remove the wastes and excess water, or balance electrolytes and acids in the blood. These imbalances result in the person not feeling as well as he/she is used to. Symptoms that some people experience during this time are:
Shortness of breath
Nausea and/or vomiting
Metal taste in the mouth
Mild to moderate depression
Decreased ability to think problems through
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What is dialysis?
The types of treatment for kidney failure include hemodialysis and peritoneal dialysis. Hemodialysis is a procedure that removes extra fluid, electrolytes and wastes using a dialysis machine either at home or at a dialysis center. Peritoneal dialysis is a type of dialysis that removes extra fluid, electrolytes and wastes using the lining of the abdominal cavity (peritoneum). There are two types of peritoneal dialysis: Continuous ambulatory perintoneal dialysis (CAPD) is dialysis that is done on a continuous basis with exchanges four times a day. Continuous cyclic peritoneal dialysis (CCPD) is dialysis that is done during the night using a machine to make the exchanges while you sleep.
What is a transplant?
With transplantation, a healthy kidney is placed in the lower abdomen and takes over the function of the failed kidneys. Transplantation is usually a better long-term treatment than dialysis. Experience has shown us that ADPKD patients generally do well following kidney transplantation. Many transplant kidneys have worked well for 10-20 years, but others have stopped working sooner. With current medications to suppress rejection (the process by which the body tends to fight the transplanted kidney), 75 percent to 80 percent of transplanted kidneys work adequately for at least five years. There are many new drugs being developed, and it is hoped that some of these new medications will help to keep the transplanted kidney functioning for many years.