Polycystic Kidney Disease Essay
Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous cysts in the kidneys. The kidneys are two organs, each about the size of a fist, located in the upper part of a person's abdomen, toward the back. The kidneys filter wastes and extra fluid from the blood to form urine. They also regulate amounts of certain vital substances in the body. When cysts form in the kidneys, they are filled with fluid. PKD cysts can profoundly enlarge the kidneys while replacing much of the normal structure, resulting in reduced kidney function and leading to kidney failure.
When PKD causes kidneys to fail-which usually happens after many years-the patient requires dialysis or kidney transplantation. About one-half of people with the most common type of PKD progress to kidney failure, also called …show more content…
end-stage renal disease (ESRD).
PKD can also cause cysts in the liver and problems in other organs, such as blood vessels in the brain and heart. The number of cysts as well as the complications they cause help doctors distinguish PKD from the usually harmless "simple" cysts that often form in the kidneys in later years of life.
In the United States, about 600,000 people have PKD, and cystic disease is the fourth leading cause of kidney failure. Two major inherited forms of PKD exist:
Autosomal dominant PKD is the most common inherited form. Symptoms usually develop between the ages of 30 and 40, but they can begin earlier, even in childhood. About 90 percent of all PKD cases are autosomal dominant PKD.
Autosomal recessive PKD is a rare inherited form. Symptoms of autosomal recessive PKD begin in the earliest months of life, even in the womb
Autosomal dominant PKD is the most common inherited disorder of the kidneys. The phrase “autosomal dominant” means that if one parent has the disease, there is a 50 percent chance that the disease gene will pass to a child. In some cases—perhaps 10 percent—autosomal dominant PKD occurs spontaneously in patients. In these cases, neither of the parents carries a copy of the disease gene.
Many people with autosomal dominant PKD live for several decades without developing symptoms. For this reason, autosomal dominant PKD is often called “adult polycystic kidney disease.” Yet, in some cases, cysts may form earlier in life and grow quickly, causing symptoms in childhood
The cysts grow out of nephrons, the tiny filtering units inside the kidneys. The cysts eventually separate from the nephrons and continue to enlarge. The kidneys enlarge along with the cysts—which can number in the thousands—while roughly retaining their kidney shape. In fully developed autosomal dominant PKD, a cyst-filled kidney can weigh as much as 20 to 30 pounds. High blood pressure is common and develops in most patients by age 20 or 30.
What are the symptoms of autosomal dominant PKD?
The most common symptoms are pain in the back and the sides—between the ribs and hips—and headaches. The pain can be temporary or persistent, mild or severe.
People with autosomal dominant PKD also can experience the following complications: urinary tract infections—specifically, in the kidney cysts hematuria—blood in the urine liver and pancreatic cysts abnormal heart valves high blood pressure kidney stones aneurysms—bulges in the walls of blood vessels—in the brain diverticulosis—small pouches bulge outward through the colon
How is autosomal dominant PKD diagnosed?
Autosomal dominant PKD is usually diagnosed by kidney imaging studies. The most common form of diagnostic kidney imaging is ultrasound, but more precise studies, such as computerized tomography (CT) scans or magnetic resonance imaging (MRI) are also widely used. In autosomal dominant PKD, the onset of kidney damage and how quickly the disease progresses can vary. Kidney imaging findings can also vary considerably, depending on a patient’s age. Younger patients usually have both fewer and smaller cysts. Doctors have therefore developed specific criteria for diagnosing 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 family 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 unnoticed. Physical checkups and blood and urine tests may not lead to early diagnosis. Because of the slow, undetected progression of cyst growth, some people live for many years without knowing they have autosomal dominant PKD.
Once cysts have grown to about one-half inch, however, diagnosis is possible with imaging technology. Ultrasound, which passes sound waves through the body to create a picture of the kidneys, is used most often. Ultrasound imaging does not use any injected dyes or radiation and is safe for all patients, including pregnant women. It can also detect cysts in the kidneys of a fetus, but large cyst growth this early in life is uncommon in autosomal dominant PKD.
More powerful and expensive imaging procedures such as CT scans and MRI also can detect cysts. Recently, MRI has been used to measure kidney and cyst volume and monitor kidney and cyst growth, which may serve as a way to track progression of the disease.
Although a cure for autosomal dominant PKD is not available, treatment can ease symptoms and prolong life.
Pain. Pain in the area of the kidneys can be caused by cyst infection, bleeding into cysts, kidney stone, or stretching of the fibrous tissue around the kidney with cyst growth. A doctor will first evaluate which of these causes are contributing to the pain to guide treatment. If it is determined to be chronic pain due to cyst expansion, the doctor may initially suggest over-the-counter pain medications, such as aspirin or acetaminophen (Tylenol). Consult your doctor before taking any over-the-counter medication because some may be harmful to the kidneys. For most but not all cases of severe pain due to cyst expansion, surgery to shrink cysts can relieve pain in the back and sides. However, surgery provides only temporary relief and does not slow the disease’s progression toward kidney failure.
Headaches that are severe or that seem to feel different from other headaches might be caused by aneurysms—blood vessels that balloon out in spots—in the brain.
These aneurysms could rupture, which can have severe consequences. Headaches also can be caused by high blood pressure. People with autosomal dominant PKD should see a doctor if they have severe or recurring headaches—even before considering over-the-counter pain medications.
Urinary tract infections. People with autosomal dominant PKD tend to have frequent urinary tract infections, which can be treated with antibiotics. People with the disease should seek treatment for urinary tract infections immediately because infection can spread from the urinary tract to the cysts in the kidneys. Cyst infections are difficult to treat because many antibiotics do not penetrate the cysts.
High blood pressure. Keeping blood pressure under control can slow the effects of autosomal dominant PKD. Lifestyle changes and various medications can lower high blood pressure. Patients should ask their doctors about such treatments. Sometimes proper diet and exercise are enough to keep blood pressure
controlled.
End-stage renal disease. After many years, PKD can cause the kidneys to fail. Because kidneys are essential for life, people with ESRD must seek one of two options for replacing kidney functions: dialysis or transplantation. In hemodialysis, blood is circulated into an external filter, where it is cleaned before re-entering the body; in peritoneal dialysis, a fluid is introduced into the abdomen, where it absorbs wastes and is then removed. Transplantation of healthy kidneys into ESRD patients has become a common and successful procedure. Healthy—non-PKD—kidneys transplanted into PKD patients do not develop cysts.
Points to Remember
The two forms of polycystic kidney disease (PKD) are autosomal dominant PKD, a form that usually causes symptoms in adulthood autosomal recessive PKD, a rare form that usually causes symptoms in infancy and early childhood
The symptoms and signs of PKD include pain in the back and lower sides headaches urinary tract infections blood in the urine cysts in the kidneys and other organs
Diagnosis of PKD is obtained by ultrasound imaging of kidney cysts ultrasound imaging of cysts in other organs 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
Hope through Research
Scientists have begun to identify the processes that trigger formation of PKD cysts. Advances in the field of genetics have increased our understanding of the abnormal genes responsible for autosomal dominant and autosomal recessive PKD. Scientists have located two genes associated with autosomal dominant PKD. The first was located in 1985 on chromosome 16 and labeled PKD1. PKD2 was localized to chromosome 4 in 1993. Within 3 years, scientists had isolated the proteins these two genes produce—polycystin-1 and polycystin-2.
When both the PKD1 and PKD2 genes are normal, the proteins they produce work together to foster normal kidney development and inhibit cyst formation. A mutation in either of the genes can lead to cyst formation, but evidence suggests that disease development also requires other factors, in addition to the mutation in one of the PKD genes.
Genetic analyses of most families with PKD confirm mutations in either the PKD1 or PKD2 gene. In about 10 to 15 percent of cases, however, families with autosomal dominant PKD do not show obvious abnormalities 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 testing for autosomal recessive PKD to detect mutations in PKHD1 is now offered by a limited number of molecular genetic diagnostics laboratories in the United States.
Researchers have bred rodents with a genetic disease that parallels both inherited forms of human PKD. Studying these mice will lead to greater understanding of the genetic and nongenetic mechanisms involved in cyst formation. In recent years, researchers have discovered several compounds that appear to inhibit cyst formation in mice with the PKD gene. Some of these compounds are in clinical testing in humans. Scientists hope further testing will lead to safe and effective treatments for humans with the disease.
Recent clinical studies of autosomal dominant PKD are exploring new imaging methods for tracking progression of cystic kidney disease. These methods, using MRI, are helping scientists design better clinical trials for new treatments of autosomal dominant PKD.
People interested in participating in clinical trials of new treatments for PKD can find a list of centers recruiting patients at www.ClinicalTrials.gov. http://kidney.niddk.nih.gov/kudiseases/pubs/polycystic/ Autosomal Dominant Polycystic Kidney Disease
YESTERDAY
Autosomal Dominant Polycystic Kidney Disease (ADPKD) resulted in end-stage renal disease (ESRD) by age 53, on average, and was responsible for 6 percent of ESRD cases in the U.S.
The details of the genetics of ADPKD were unknown other than the observation that 50 percent of children born to an affected parent would develop the disease.
Diagnosis of well-established ADPKD in adults was relatively straightforward with available imaging techniques (ultrasound and computerized tomography). Diagnosis of earlier stages of disease in children and young adults was much more difficult.
Few treatments were available for chronic kidney disease in general, and there was no specific therapy for ADPKD. The importance of controlling blood pressure and dietary protein intake in patients with chronic kidney disease was not recognized.
Two lifesaving kidney function replacement therapies—hemodialysis and kidney transplantation, developed through fundamental NIH research in the 1960s—were increasingly available for ADPKD patients; however, neither was ideal. Because the genetics of ADPKD were not understood, some transplant centers were unwilling to perform transplants from family members who wished to donate a kidney.
TODAY
Through NIH-supported research, mutations in one of two genes—PKD1 and PKD2—have been identified in eighty five percent of patients with ADPKD. NIH funded studies are searching for additional genetic changes that might explain person to person variation in kidney growth and disease severity.
Development of age-specific diagnostic criteria and genetic testing has facilitated early diagnosis of ADPKD. Newer imaging methods, specifically magnetic resonance imaging, provide better kidney cyst imaging.
The ability to detect mutations in either PKD1 or PKD2 provides important prognostic information. NIH-supported clinical studies have shown that patients with mutations in PKD2 tend to develop kidney cysts, high blood pressure, and ESRD at a later age than do patients with mutations in PKD1.
Although the molecular mechanisms by which PKD1 and PKD2 mutations cause ADPKD are not known, NIH-supported researchers have studied how these genes are involved in basic biological processes within kidney cells, and are exploring new avenues of investigation to understand how mutations might cause kidney cysts.
The NIH funded two large clinical studies of ADPKD. The Consortium for Radiologic Imaging of PKD (CRISP) provided new and useful information regarding the reliability of non-invasive magnetic resonance imaging for monitoring disease progression in patients with ADPKD. The HALT-PKD study is using these imaging methods to test whether newer classes of blood pressure medications can prevent or delay progression of kidney size functional decline in ADPKD.
Basic research supported by NIH facilitates testing of other potential drug therapies for ADPKD , and other clinical trials of ADPKD are implementing new imaging methods for assessing progression of ADPKD.
The average age for development of ESRD for patients with ADPKD has increased from 53 to 57 years of age. ADPKD is currently responsible for 4.5 percent of overall ESRD cases and 2.2 percent of new ESRD cases each year in the U.S.
The high cardiovascular death rate in dialysis patients with ADPKD remains a problem.
Kidney transplantation is widely available, and nearly 13 percent of ADPKD patients who develop ESRD receive a transplant before beginning dialysis therapy. Limited organ availability has resulted in longer waiting times.
Transplant failure due to acute organ rejection is much less common, with one-year success rates exceeding 90 percent.
TOMORROW
The continued development and testing of new potential therapies for chronic kidney disease in general—and ADPKD in particular—will result in fewer people developing advanced kidney disease and kidney failure. This in turn will result in less need for dialysis and transplantation.
As our understanding of the genetics and progression of ADPKD increases, we hope that there will be a decrease in the number of ADPKD patients that progress to ESRD.
Because ADPKD can affect patients very differently, even within the same family, the NIH is assembling a large genetic sample collection for future investigations that would identify genetic markers that might predict who will develop more rapidly progressive kidney disease. These genetic studies could also provide new information on identifying key disease pathways and help design new drug treatment strategies. The studies also may yield clues about how to intervene earlier, more precisely, and more effectively in ADPKD.
The results of the HALT-PKD trials should help NIH extend the success of therapies for other forms of kidney injury to ADPKD, by testing interventions that can control the accelerated development of cardiovascular disease, the main cause of death in kidney patients. Other ongoing studies supported by NIH will determine new risk factors for accelerated cardiovascular disease, and permit individualized prevention strategies.
If detected sufficiently early, it may be possible to restore lost kidney function. More aggressive management of diabetes and high blood pressure, as well as drugs that target kidney fibrosis, may give patients additional years of life without dialysis.
For those patients who need dialysis, NIH is studying whether more frequent dialysis improves physical function and cardiovascular health. Studies are also underway to examine the factors that influence the functioning of fistulas—a surgically-created site used to access blood—in patients undergoing hemodialysis.
Despite our best immunosuppressant therapies, a number of patients with kidney transplants still lose their transplanted kidney due to chronic rejection. Better strategies to maintain the function of transplanted kidneys and prevent chronic scarring are likely to emerge from on-going basic research and improved imaging methods.
For more information, contact The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
When PKD causes kidneys to fail-which usually happens after many years-the patient requires dialysis or kidney transplantation. About one-half of people with the most common type of PKD progress to kidney failure, also called …show more content…
end-stage renal disease (ESRD).
PKD can also cause cysts in the liver and problems in other organs, such as blood vessels in the brain and heart. The number of cysts as well as the complications they cause help doctors distinguish PKD from the usually harmless "simple" cysts that often form in the kidneys in later years of life.
In the United States, about 600,000 people have PKD, and cystic disease is the fourth leading cause of kidney failure. Two major inherited forms of PKD exist:
Autosomal dominant PKD is the most common inherited form. Symptoms usually develop between the ages of 30 and 40, but they can begin earlier, even in childhood. About 90 percent of all PKD cases are autosomal dominant PKD.
Autosomal recessive PKD is a rare inherited form. Symptoms of autosomal recessive PKD begin in the earliest months of life, even in the womb
Autosomal dominant PKD is the most common inherited disorder of the kidneys. The phrase “autosomal dominant” means that if one parent has the disease, there is a 50 percent chance that the disease gene will pass to a child. In some cases—perhaps 10 percent—autosomal dominant PKD occurs spontaneously in patients. In these cases, neither of the parents carries a copy of the disease gene.
Many people with autosomal dominant PKD live for several decades without developing symptoms. For this reason, autosomal dominant PKD is often called “adult polycystic kidney disease.” Yet, in some cases, cysts may form earlier in life and grow quickly, causing symptoms in childhood
The cysts grow out of nephrons, the tiny filtering units inside the kidneys. The cysts eventually separate from the nephrons and continue to enlarge. The kidneys enlarge along with the cysts—which can number in the thousands—while roughly retaining their kidney shape. In fully developed autosomal dominant PKD, a cyst-filled kidney can weigh as much as 20 to 30 pounds. High blood pressure is common and develops in most patients by age 20 or 30.
What are the symptoms of autosomal dominant PKD?
The most common symptoms are pain in the back and the sides—between the ribs and hips—and headaches. The pain can be temporary or persistent, mild or severe.
People with autosomal dominant PKD also can experience the following complications: urinary tract infections—specifically, in the kidney cysts hematuria—blood in the urine liver and pancreatic cysts abnormal heart valves high blood pressure kidney stones aneurysms—bulges in the walls of blood vessels—in the brain diverticulosis—small pouches bulge outward through the colon
How is autosomal dominant PKD diagnosed?
Autosomal dominant PKD is usually diagnosed by kidney imaging studies. The most common form of diagnostic kidney imaging is ultrasound, but more precise studies, such as computerized tomography (CT) scans or magnetic resonance imaging (MRI) are also widely used. In autosomal dominant PKD, the onset of kidney damage and how quickly the disease progresses can vary. Kidney imaging findings can also vary considerably, depending on a patient’s age. Younger patients usually have both fewer and smaller cysts. Doctors have therefore developed specific criteria for diagnosing 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 family 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 unnoticed. Physical checkups and blood and urine tests may not lead to early diagnosis. Because of the slow, undetected progression of cyst growth, some people live for many years without knowing they have autosomal dominant PKD.
Once cysts have grown to about one-half inch, however, diagnosis is possible with imaging technology. Ultrasound, which passes sound waves through the body to create a picture of the kidneys, is used most often. Ultrasound imaging does not use any injected dyes or radiation and is safe for all patients, including pregnant women. It can also detect cysts in the kidneys of a fetus, but large cyst growth this early in life is uncommon in autosomal dominant PKD.
More powerful and expensive imaging procedures such as CT scans and MRI also can detect cysts. Recently, MRI has been used to measure kidney and cyst volume and monitor kidney and cyst growth, which may serve as a way to track progression of the disease.
Although a cure for autosomal dominant PKD is not available, treatment can ease symptoms and prolong life.
Pain. Pain in the area of the kidneys can be caused by cyst infection, bleeding into cysts, kidney stone, or stretching of the fibrous tissue around the kidney with cyst growth. A doctor will first evaluate which of these causes are contributing to the pain to guide treatment. If it is determined to be chronic pain due to cyst expansion, the doctor may initially suggest over-the-counter pain medications, such as aspirin or acetaminophen (Tylenol). Consult your doctor before taking any over-the-counter medication because some may be harmful to the kidneys. For most but not all cases of severe pain due to cyst expansion, surgery to shrink cysts can relieve pain in the back and sides. However, surgery provides only temporary relief and does not slow the disease’s progression toward kidney failure.
Headaches that are severe or that seem to feel different from other headaches might be caused by aneurysms—blood vessels that balloon out in spots—in the brain.
These aneurysms could rupture, which can have severe consequences. Headaches also can be caused by high blood pressure. People with autosomal dominant PKD should see a doctor if they have severe or recurring headaches—even before considering over-the-counter pain medications.
Urinary tract infections. People with autosomal dominant PKD tend to have frequent urinary tract infections, which can be treated with antibiotics. People with the disease should seek treatment for urinary tract infections immediately because infection can spread from the urinary tract to the cysts in the kidneys. Cyst infections are difficult to treat because many antibiotics do not penetrate the cysts.
High blood pressure. Keeping blood pressure under control can slow the effects of autosomal dominant PKD. Lifestyle changes and various medications can lower high blood pressure. Patients should ask their doctors about such treatments. Sometimes proper diet and exercise are enough to keep blood pressure
controlled.
End-stage renal disease. After many years, PKD can cause the kidneys to fail. Because kidneys are essential for life, people with ESRD must seek one of two options for replacing kidney functions: dialysis or transplantation. In hemodialysis, blood is circulated into an external filter, where it is cleaned before re-entering the body; in peritoneal dialysis, a fluid is introduced into the abdomen, where it absorbs wastes and is then removed. Transplantation of healthy kidneys into ESRD patients has become a common and successful procedure. Healthy—non-PKD—kidneys transplanted into PKD patients do not develop cysts.
Points to Remember
The two forms of polycystic kidney disease (PKD) are autosomal dominant PKD, a form that usually causes symptoms in adulthood autosomal recessive PKD, a rare form that usually causes symptoms in infancy and early childhood
The symptoms and signs of PKD include pain in the back and lower sides headaches urinary tract infections blood in the urine cysts in the kidneys and other organs
Diagnosis of PKD is obtained by ultrasound imaging of kidney cysts ultrasound imaging of cysts in other organs 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
Hope through Research
Scientists have begun to identify the processes that trigger formation of PKD cysts. Advances in the field of genetics have increased our understanding of the abnormal genes responsible for autosomal dominant and autosomal recessive PKD. Scientists have located two genes associated with autosomal dominant PKD. The first was located in 1985 on chromosome 16 and labeled PKD1. PKD2 was localized to chromosome 4 in 1993. Within 3 years, scientists had isolated the proteins these two genes produce—polycystin-1 and polycystin-2.
When both the PKD1 and PKD2 genes are normal, the proteins they produce work together to foster normal kidney development and inhibit cyst formation. A mutation in either of the genes can lead to cyst formation, but evidence suggests that disease development also requires other factors, in addition to the mutation in one of the PKD genes.
Genetic analyses of most families with PKD confirm mutations in either the PKD1 or PKD2 gene. In about 10 to 15 percent of cases, however, families with autosomal dominant PKD do not show obvious abnormalities 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 testing for autosomal recessive PKD to detect mutations in PKHD1 is now offered by a limited number of molecular genetic diagnostics laboratories in the United States.
Researchers have bred rodents with a genetic disease that parallels both inherited forms of human PKD. Studying these mice will lead to greater understanding of the genetic and nongenetic mechanisms involved in cyst formation. In recent years, researchers have discovered several compounds that appear to inhibit cyst formation in mice with the PKD gene. Some of these compounds are in clinical testing in humans. Scientists hope further testing will lead to safe and effective treatments for humans with the disease.
Recent clinical studies of autosomal dominant PKD are exploring new imaging methods for tracking progression of cystic kidney disease. These methods, using MRI, are helping scientists design better clinical trials for new treatments of autosomal dominant PKD.
People interested in participating in clinical trials of new treatments for PKD can find a list of centers recruiting patients at www.ClinicalTrials.gov. http://kidney.niddk.nih.gov/kudiseases/pubs/polycystic/ Autosomal Dominant Polycystic Kidney Disease
YESTERDAY
Autosomal Dominant Polycystic Kidney Disease (ADPKD) resulted in end-stage renal disease (ESRD) by age 53, on average, and was responsible for 6 percent of ESRD cases in the U.S.
The details of the genetics of ADPKD were unknown other than the observation that 50 percent of children born to an affected parent would develop the disease.
Diagnosis of well-established ADPKD in adults was relatively straightforward with available imaging techniques (ultrasound and computerized tomography). Diagnosis of earlier stages of disease in children and young adults was much more difficult.
Few treatments were available for chronic kidney disease in general, and there was no specific therapy for ADPKD. The importance of controlling blood pressure and dietary protein intake in patients with chronic kidney disease was not recognized.
Two lifesaving kidney function replacement therapies—hemodialysis and kidney transplantation, developed through fundamental NIH research in the 1960s—were increasingly available for ADPKD patients; however, neither was ideal. Because the genetics of ADPKD were not understood, some transplant centers were unwilling to perform transplants from family members who wished to donate a kidney.
TODAY
Through NIH-supported research, mutations in one of two genes—PKD1 and PKD2—have been identified in eighty five percent of patients with ADPKD. NIH funded studies are searching for additional genetic changes that might explain person to person variation in kidney growth and disease severity.
Development of age-specific diagnostic criteria and genetic testing has facilitated early diagnosis of ADPKD. Newer imaging methods, specifically magnetic resonance imaging, provide better kidney cyst imaging.
The ability to detect mutations in either PKD1 or PKD2 provides important prognostic information. NIH-supported clinical studies have shown that patients with mutations in PKD2 tend to develop kidney cysts, high blood pressure, and ESRD at a later age than do patients with mutations in PKD1.
Although the molecular mechanisms by which PKD1 and PKD2 mutations cause ADPKD are not known, NIH-supported researchers have studied how these genes are involved in basic biological processes within kidney cells, and are exploring new avenues of investigation to understand how mutations might cause kidney cysts.
The NIH funded two large clinical studies of ADPKD. The Consortium for Radiologic Imaging of PKD (CRISP) provided new and useful information regarding the reliability of non-invasive magnetic resonance imaging for monitoring disease progression in patients with ADPKD. The HALT-PKD study is using these imaging methods to test whether newer classes of blood pressure medications can prevent or delay progression of kidney size functional decline in ADPKD.
Basic research supported by NIH facilitates testing of other potential drug therapies for ADPKD , and other clinical trials of ADPKD are implementing new imaging methods for assessing progression of ADPKD.
The average age for development of ESRD for patients with ADPKD has increased from 53 to 57 years of age. ADPKD is currently responsible for 4.5 percent of overall ESRD cases and 2.2 percent of new ESRD cases each year in the U.S.
The high cardiovascular death rate in dialysis patients with ADPKD remains a problem.
Kidney transplantation is widely available, and nearly 13 percent of ADPKD patients who develop ESRD receive a transplant before beginning dialysis therapy. Limited organ availability has resulted in longer waiting times.
Transplant failure due to acute organ rejection is much less common, with one-year success rates exceeding 90 percent.
TOMORROW
The continued development and testing of new potential therapies for chronic kidney disease in general—and ADPKD in particular—will result in fewer people developing advanced kidney disease and kidney failure. This in turn will result in less need for dialysis and transplantation.
As our understanding of the genetics and progression of ADPKD increases, we hope that there will be a decrease in the number of ADPKD patients that progress to ESRD.
Because ADPKD can affect patients very differently, even within the same family, the NIH is assembling a large genetic sample collection for future investigations that would identify genetic markers that might predict who will develop more rapidly progressive kidney disease. These genetic studies could also provide new information on identifying key disease pathways and help design new drug treatment strategies. The studies also may yield clues about how to intervene earlier, more precisely, and more effectively in ADPKD.
The results of the HALT-PKD trials should help NIH extend the success of therapies for other forms of kidney injury to ADPKD, by testing interventions that can control the accelerated development of cardiovascular disease, the main cause of death in kidney patients. Other ongoing studies supported by NIH will determine new risk factors for accelerated cardiovascular disease, and permit individualized prevention strategies.
If detected sufficiently early, it may be possible to restore lost kidney function. More aggressive management of diabetes and high blood pressure, as well as drugs that target kidney fibrosis, may give patients additional years of life without dialysis.
For those patients who need dialysis, NIH is studying whether more frequent dialysis improves physical function and cardiovascular health. Studies are also underway to examine the factors that influence the functioning of fistulas—a surgically-created site used to access blood—in patients undergoing hemodialysis.
Despite our best immunosuppressant therapies, a number of patients with kidney transplants still lose their transplanted kidney due to chronic rejection. Better strategies to maintain the function of transplanted kidneys and prevent chronic scarring are likely to emerge from on-going basic research and improved imaging methods.
For more information, contact The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):