Polycystic Kidney Disease

National Kidney and Urologic Diseases Information Clearinghouse

Polycystic kidney disease (PKD) is a genetic In the United States, about 600,0001 people disorder characterized by the growth of have PKD, and cystic disease is the fourth numerous cysts in the kidneys. The kidneys leading cause of kidney failure. Two major

National are two organs, each about the size of a inherited forms of PKD exist: Institute of fist, located in the upper part of a person’s Diabetes and abdomen, toward the back. The kidneys • Autosomal dominant PKD is the most Digestive common inherited form. Symptoms and Kidney filter wastes and extra fluid from the blood Diseases to form urine. They also regulate amounts usually develop between the ages of 30 and 40, but they can begin earlier, NATIONAL of certain vital substances in the body. INSTITUTES When cysts form in the kidneys, they are even in childhood. About 90 percent OF HEALTH filled with fluid. PKD cysts can profoundly of all PKD cases are autosomal domi­ enlarge the kidneys while replacing much of nant PKD. the normal structure, resulting in reduced • Autosomal recessive PKD is a rare kidney function and leading to kidney inherited form. Symptoms of autoso­ failure. mal recessive PKD begin in the earliest When PKD causes kidneys to fail—which months of life, even in the womb. usually happens after many years—the patient requires dialysis or kidney trans­ Autosomal Dominant PKD plantation. About one-half of people with What is autosomal the most common type of PKD progress to kidney failure, also called end-stage renal dominant PKD? disease (ESRD). Autosomal dominant PKD is the most com­ mon inherited disorder of the kidneys. The PKD can also cause cysts in the liver and phrase “autosomal dominant” means that problems in other organs, such as blood ves­ if one parent has the disease, there is a 50 sels in the brain and heart. The number of percent chance that the disease gene will cysts as well as the complications they cause pass to a child. In some cases—perhaps 10 help doctors distinguish PKD from the usu­ percent—autosomal dominant PKD occurs ally harmless “simple” cysts that often form spontaneously in patients. In these cases, in the kidneys in later years of life. neither of the parents carries a copy of the disease gene.

1 Grantham JJ, Nair V, Winklhoffer F. Cystic diseases U.S. Department of the kidney. In: Brenner BM, ed. Brenner & of Health and Rector’s The Kidney. Vol. 2. 6th ed. Philadelphia: Human Services WB Saunders Company; 2000: 1699–1730. Many people with autosomal dominant What are the symptoms of PKD live for several decades without autosomal dominant PKD? developing symptoms. For this reason, autosomal dominant PKD is often called The most common symptoms are pain in “adult polycystic kidney disease.” Yet, in the back and the sides—between the ribs some cases, cysts may form earlier in life and hips—and headaches. The pain can be and grow quickly, causing symptoms in temporary or persistent, mild or severe. childhood. People with autosomal dominant PKD also can experience the following complications: • urinary tract infections—specifically, in the kidney cysts • hematuria—blood in the urine Cysts • liver and pancreatic cysts

Ureter • abnormal heart valves • high blood pressure • kidney stones Polycystic kidney • aneurysms—bulges in the walls of blood vessels—in the brain • diverticulosis—small pouches bulge outward through the colon Healthy kidney How is autosomal dominant The polycystic kidney roughly retains the same shape as the healthy kidney. PKD diagnosed? Autosomal dominant PKD is usually diagnosed by kidney imaging studies. The The cysts grow out of nephrons, the tiny most common form of diagnostic kidney filtering units inside the kidneys. The cysts imaging is ultrasound, but more precise eventually separate from the nephrons and studies, such as computerized tomography continue to enlarge. The kidneys enlarge (CT) scans or magnetic resonance imaging along with the cysts—which can number (MRI) are also widely used. In autosomal in the thousands—while roughly retain­ dominant PKD, the onset of kidney damage ing their kidney shape. In fully developed and how quickly the disease progresses can autosomal dominant PKD, a cyst-filled kid­ vary. Kidney imaging findings can also vary ney can weigh as much as 20 to 30 pounds. considerably, depending on a patient’s age. High blood pressure is common and devel­ Younger patients usually have both fewer ops in most patients by age 20 or 30. and smaller cysts. Doctors have therefore developed specific criteria for diagnosing

2 Polycystic Kidney Disease the disease with kidney imaging findings, depending on patient age. For example, the presence of at least two cysts in each kidney by age 30 in a patient with a fam­ ily history of the disease can confirm the diagnosis of autosomal dominant PKD. If there is any question about the diagnosis, a family history of autosomal dominant PKD and cysts found in other organs make the diagnosis more likely. In most cases of autosomal dominant PKD, patients have no symptoms and their physical condition appears normal for many years, so the disease can go unno­ An ultrasound imaging device passes harmless sound ticed. Physical checkups and blood and waves through the body to detect possible kidney cysts. urine tests may not lead to early diagnosis. Because of the slow, undetected progres­ Diagnosis can also be made with a genetic sion of cyst growth, some people live for test that detects mutations in the autoso­ many years without knowing they have mal dominant PKD genes, called PKD1 autosomal dominant PKD. and PKD2. Although this test can detect the presence of the autosomal dominant Once cysts have grown to about one-half PKD mutations before large cysts develop, inch, however, diagnosis is possible with its usefulness is limited by two factors: imaging technology. Ultrasound, which detection of a disease gene cannot predict passes sound waves through the body to the onset of symptoms or ultimate sever­ create a picture of the kidneys, is used ity of the disease, and if a disease gene is most often. Ultrasound imaging does not detected, no specific prevention or cure use any injected dyes or radiation and is for the disease exists. However, a young safe for all patients, including pregnant person who knows of a PKD gene mutation women. It can also detect cysts in the may be able to forestall the loss of kidney kidneys of a fetus, but large cyst growth function through diet and blood pressure this early in life is uncommon in autosomal control. The genetic test may also be used dominant PKD. to determine whether a young member of a More powerful and expensive imaging PKD family can safely donate a kidney to a procedures such as CT scans and MRI also family member with the disease. Individu­ can detect cysts. Recently, MRI has been als with a family history of PKD who are of used to measure kidney and cyst volume childbearing age might also want to know and monitor kidney and cyst growth, which whether they have the potential of passing may serve as a way to track progression of a PKD gene to a child. Anyone considering the disease. genetic testing should receive counseling to understand all the implications of the test.

3 Polycystic Kidney Disease How is autosomal dominant Urinary tract infections. People with PKD treated? autosomal dominant PKD tend to have frequent urinary tract infections, which can Although a cure for autosomal dominant be treated with antibiotics. People with the PKD is not available, treatment can ease disease should seek treatment for urinary symptoms and prolong life. tract infections immediately because infec­ Pain. Pain in the area of the kidneys tion can spread from the urinary tract to can be caused by cyst infection, bleeding the cysts in the kidneys. Cyst infections are into cysts, kidney stone, or stretching of difficult to treat because many antibiotics the fibrous tissue around the kidney with do not penetrate the cysts. cyst growth. A doctor will first evaluate High blood pressure. Keeping blood pres­ which of these causes are contributing sure under control can slow the effects to the pain to guide treatment. If it is of autosomal dominant PKD. Lifestyle determined to be chronic pain due to cyst changes and various medications can lower expansion, the doctor may initially sug­ high blood pressure. Patients should ask gest over-the-counter pain medications, their doctors about such treatments. Some­ such as aspirin or acetaminophen (Tyle­ times proper diet and exercise are enough nol). Consult your doctor before taking to keep blood pressure controlled. any over-the-counter medication because some may be harmful to the kidneys. For End-stage renal disease. After many years, most but not all cases of severe pain due PKD can cause the kidneys to fail. Because to cyst expansion, surgery to shrink cysts kidneys are essential for life, people with can relieve pain in the back and sides. ESRD must seek one of two options for However, surgery provides only tempo­ replacing kidney functions: dialysis or rary relief and does not slow the disease’s transplantation. In hemodialysis, blood is progression toward kidney failure. circulated into an external filter, where it is cleaned before re-entering the body; in Headaches that are severe or that seem to peritoneal dialysis, a fluid is introduced into feel different from other headaches might the abdomen, where it absorbs wastes and be caused by aneurysms—blood vessels is then removed. Transplantation of healthy that balloon out in spots—in the brain. kidneys into ESRD patients has become These aneurysms could rupture, which can a common and successful procedure. have severe consequences. Headaches Healthy—non-PKD—kidneys transplanted also can be caused by high blood pressure. into PKD patients do not develop cysts. People with autosomal dominant PKD should see a doctor if they have severe or recurring headaches—even before consid­ ering over-the-counter pain medications.

4 Polycystic Kidney Disease Autosomal Recessive PKD What are the symptoms of What is autosomal recessive autosomal recessive PKD? PKD? Children with autosomal recessive PKD experience high blood pressure, urinary Autosomal recessive PKD is caused by a tract infections, and frequent urination. mutation in the autosomal recessive PKD The disease usually affects the liver and gene, called PKHD1. Other genes for the spleen, resulting in low blood cell counts, disease might exist but have not yet been varicose veins, and hemorrhoids. Because discovered by scientists. We all carry two kidney function is crucial for early physi­ copies of every gene. Parents who do not cal development, children with autosomal have PKD can have a child with the disease recessive PKD and decreased kidney func­ if both parents carry one copy of the abnor­ tion are usually smaller than average size. mal gene and both pass that gene copy to Recent studies suggest that growth prob­ their baby. The chance of the child having lems may be a primary feature of autosomal autosomal recessive PKD when both par­ recessive PKD. ents carry the abnormal gene is 25 percent. If only one parent carries the abnormal How is autosomal recessive PKD gene, the baby cannot get autosomal reces­ diagnosed? sive PKD but could ultimately pass the abnormal gene to his or her children. Ultrasound imaging of the fetus or newborn reveals enlarged kidneys with an abnormal The signs of autosomal recessive PKD appearance, but large cysts such as those in frequently begin before birth, so it is often autosomal dominant PKD are rarely seen. called “infantile PKD.” Children born Because autosomal recessive PKD tends with autosomal recessive PKD often, but to scar the liver, ultrasound imaging of the not always, develop kidney failure before liver also aids in diagnosis. reaching adulthood. Severity of the dis­ ease varies. Babies with the worst cases die How is autosomal recessive PKD hours or days after birth due to respiratory treated? difficulties or respiratory failure. Medicines can control high blood pressure Some people with autosomal recessive PKD in autosomal recessive PKD, and antibiotics do not develop symptoms until later in can control urinary tract infections. Eat­ childhood or even adulthood. Liver scar­ ing increased amounts of nutritious food ring occurs in all patients with autosomal improves growth in children with autoso­ recessive PKD and tends to become more mal recessive PKD. In some cases, growth of a medical concern with increasing age. hormones are used. In response to kidney failure, autosomal recessive PKD patients must receive dialysis or transplantation. If serious liver disease develops, some people can undergo combined liver and kidney transplantation.

5 Polycystic Kidney Disease Hope Through Research Genetic Diseases Scientists have begun to identify the pro­ Genes are segments of DNA, the cesses that trigger formation of PKD long molecules that reside in each of cysts. Advances in the field of genetics a person’s cells. The genes, through have increased our understanding of the complex processes, build proteins for abnormal genes responsible for autosomal growth and maintenance of the body. dominant and autosomal recessive PKD. At conception, DNA—or genes—from Scientists have located two genes associ­ both parents are passed to the child. ated with autosomal dominant PKD. The first was located in 1985 on chromosome A genetic disease occurs when one or 16 and labeled PKD1. PKD2 was local­ both parents pass abnormal genes to ized to chromosome 4 in 1993. Within 3 a child at conception. If receiving an years, scientists had isolated the proteins abnormal gene from just one par­ these two genes produce—polycystin-1 and ent is enough to produce a disease in polycystin-2. the child, the disease is said to have dominant inheritance. If receiving When both the PKD1 and PKD2 genes are abnormal genes from both parents is normal, the proteins they produce work needed to produce disease in the child, together to foster normal kidney develop­ the disease is said to be recessive. A ment and inhibit cyst formation. A muta­ genetic disease can also occur through tion in either of the genes can lead to cyst a spontaneous mutation. formation, but evidence suggests that disease development also requires other The chance of acquiring a dominant factors, in addition to the mutation in one disease is higher than the chance of of the PKD genes. acquiring a recessive disease. A child who receives only one gene copy for Genetic analyses of most families with PKD a recessive disease at conception will confirm mutations in either the PKD1 or not develop the genetic disease—such PKD2 gene. In about 10 to 15 percent of as autosomal recessive PKD—but cases, however, families with autosomal could pass the gene to the following dominant PKD do not show obvious abnor­ generation. malities or mutations in the PKD1 and PKD2 genes, using current testing methods. Researchers have also recently identified the autosomal recessive PKD gene, called PKHD1, on chromosome 6. Genetic test­ ing for autosomal recessive PKD to detect mutations in PKHD1 is now offered by a limited number of molecular genetic diag­ nostics laboratories in the United States.

6 Polycystic Kidney Disease Researchers have bred rodents with a Points to Remember genetic disease that parallels both inher- The two forms of polycystic kidney disease ited forms of human PKD. Studying these (PKD) are mice will lead to greater understanding of the genetic and nongenetic mechanisms • autosomal dominant PKD, a form that involved in cyst formation. In recent years, usually causes symptoms in adulthood researchers have discovered several com- • autosomal recessive PKD, a rare pounds that appear to inhibit cyst forma- form that usually causes symptoms in tion in mice with the PKD gene. Some of infancy and early childhood these compounds are in clinical testing in humans. Scientists hope further testing will The symptoms and signs of PKD include lead to safe and effective treatments for humans with the disease. • pain in the back and lower sides Recent clinical studies of autosomal • headaches dominant PKD are exploring new imaging • urinary tract infections methods for tracking progression of cys- tic kidney disease. These methods, using • blood in the urine MRI, are helping scientists design better • cysts in the kidneys and other organs clinical trials for new treatments of autoso- mal dominant PKD. Diagnosis of PKD is obtained by People interested in participating in clini- • ultrasound imaging of kidney cysts cal trials of new treatments for PKD can • ultrasound imaging of cysts in other find a list of centers recruiting patients at organs www.ClinicalTrials.gov. • family medical history, including genetic testing PKD has no cure. Treatments include • medicine to control high blood pressure • medicine and surgery to reduce pain • antibiotics to resolve infections • dialysis to replace functions of failed kidneys • kidney transplantation

7 Polycystic Kidney Disease For More Information National Kidney and Polycystic Kidney Disease Foundation Urologic Diseases 9221 Ward Parkway, Suite 400 Information Clearinghouse Kansas City, MO 64114–3367 3 Information Way Phone: 1–800–PKD–CURE (753–2873) or Bethesda, MD 20892–3580 816–931–2600 Phone: 1–800–891–5390 Email: [email protected] Fax: 703–738–4929 Internet: www.pkdcure.org Email: [email protected] American Association of Kidney Patients Internet: www.kidney.niddk.nih.gov 3505 East Frontage Road, Suite 315 The National Kidney and Urologic Diseases Tampa, FL 33607 Information Clearinghouse (NKUDIC) is a Phone: 1–800–749–2257 or 813–636–8100 service of the National Institute of Diabetes Email: [email protected] and Digestive and Kidney Diseases (NIDDK). Internet: www.aakp.org The NIDDK is part of the National Institutes of Health of the U.S. Department of Health National Kidney Foundation and Human Services. Established in 1987, the 30 East 33rd Street Clearinghouse provides information about New York, NY 10016 diseases of the kidneys and urologic system to Phone: 1–800–622–9010 or 212–889–2210 people with kidney and urologic disorders and Internet: www.kidney.org to their families, health care professionals, and the public. The NKUDIC answers inquiries, develops and distributes publications, and works The U.S. Government does not endorse or favor any closely with professional and patient organiza- specific commercial product or company. Trade, tions and Government agencies to coordinate proprietary, or company names appearing in this resources about kidney and urologic diseases. document are used only because they are considered necessary in the context of the information provided. Publications produced by the Clearinghouse If a product is not mentioned, the omission does not are carefully reviewed by both NIDDK scien- mean or imply that the product is unsatisfactory. tists and outside experts. This publication was reviewed by Lisa Guay-Woodford, M.D., Uni- versity of Alabama at Birmingham, and Stefan You may also find additional information about this Somlo, M.D., Yale University. topic by visiting MedlinePlus at www.medlineplus.gov. This publication may contain information about medications used to treat a health condition. When this publication was prepared, the NIDDK included This publication is not copyrighted. The the most current information available. Occasion- Clearinghouse encourages users of this publication to ally, new information about medication is released. duplicate and distribute as many copies as desired. For updates or for questions about any medications, This fact sheet is also available at please contact the U.S. Food and Drug Administra- www.kidney.niddk.nih.gov. tion at 1–888–INFO–FDA (463–6332), a toll-free call, or visit their website at www.fda.gov. Consult your doctor for more information.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health

NIH Publication No. 08–4008 November 2007