NKF Supports Research Programs to Find Cures for Kidney Disease
A major function of the National Kidney Foundation (NKF) is to provide support for research that advances our understanding of kidney diseases and may ultimately find cures and better treatments for those diseases. The current Research Program includes national awards representing a total commitment of nearly 2 million dollars. Following are a few of the studies presently being conducted:
Diabetes mellitus (Type 2 adult onset) is the leading cause of chronic kidney failure, accounting for over 40 percent of the new cases each year and over 31 percent of all cases in the U.S. While scientists continue to develop new medications and improved treatment protocols to control diabetes and to slow its accompanying complications, such as diabetic kidney disease, researchers are still seeking answers to the prevention and cure of this disease.
Dr. Martin Sedlacek, M.D., an NKF Research Fellow at Mount Sinai Medical Center in New York, is addressing the particular problems of patients with diabetic kidney failure who undergo kidney transplantation. Dr. Sedlacek is working to develop a way of introducing a human insulin gene into kidney cells just before kidney transplantation. If successful, this would protect the new kidney from the diabetic injury that originally caused kidney failure. The success of this study would begin to pave the way for the development of a gene therapy that could be part of the first real cure for insulin-dependent diabetes.
Hai-Chang Huang, M.D., Ph.D., an NKF Research Fellow at the University of Texas Southwestern Medical Center, Dallas, Texas, is working to identify cellular factors that cause the kidneys to enlarge in patients with diabetes mellitus. Enlargement of the kidneys contributes to the development of renal scarring and progressive loss of kidney function. Dr. Huang's study aims at the understanding of why kidney enlargement may lead to scarring and loss of organ function, in order to develop therapeutic approaches for preventing this type of kidney failure.
Uncontrolled high blood pressure is the second leading cause of chronic kidney failure in the United States and one of the most common problems that can seriously harm the kidneys. Impairing urinary sodium excretion and volume regulation, it speeds up the progression of many forms of kidney injury. It affects about 50 million Americans (or one out of four adults), with approximately two million people being diagnosed as having high blood pressure every year. One third of the people who have high blood pressure are not even aware of it. Although scientists have developed effective medications to control high blood pressure (including a new class of drugs called ACE Inhibitors), researchers continue to work toward a more complete understanding of the role of the kidney in this condition.
Focusing on the role of the kidneys in high blood pressure, Dr. Chagriya Kitiyakara, M.R.C.P., an NKF/NKF of the National Capital Area Matching Fellow at Georgetown University Medical Center in Washington, D.C., is investigating the underlying causes of renovascular hypertension--a type of high blood pressure caused by narrowing of the arteries leading to the kidneys. Dr. Kitiyakara's work focuses on a group of chemical substances produced in the body, which are called prostaglandins. Some prostaglandins can cause blood vessels to constrict, or narrow. Prostaglandins can also activate specific pathways to the brain. Dr. Kitiyakara's studies examine the effects on blood pressure of giving drugs that block vasoconstrictor prostaglandins. He is also studying the genes associated with these prostaglandins. Since these prostaglandins not only raise blood pressure, but also promote kidney damage, salt retention, atherosclerosis and clumping of blood platelets, they may be very important in high blood pressure and its harmful effects on the kidney and blood vessels.
Ki H. Chon, Ph.D., a recipient of a Young Investigator Grant at Brown University in Providence, Rhode Island, is seeking to improve our understanding of the kidney's role in high blood pressure. Dr. Chon's investigations focus on two systems that help to control blood flow in the kidneys. These systems are known to affect the filtration rate of the glomeruli, or filtering units of the kidneys, and to influence salt and water excretion by the kidneys. Dr. Chon is investigating the changes that occur in the way these two control systems interact. His goal is to understand the significance of these changes in the development of high blood pressure.
The glomeruli are the kidney's filtering units. When the glomeruli are injured by trauma or other particular diseases, the kidney has difficulty cleansing the blood and getting rid of wastes and extra fluid in the body. Focal glomerulosclerosis (FGS) is one of more than 20 types of glomerular disorders, and one which often causes permanent kidney failure in adults and children. Some cases of FGS with progression to chronic kidney failure are associated with conditions such as reflux, heroin and HIV nephropathies, but in most cases the cause is unknown. Also of interest is the fact that some individuals with predisposing conditions (such as AIDS or high blood pressure) do not progress from FGS to chronic kidney failure.
Martin R. Pollak, M.D., an NKF Clinical Scientist at Brigham and Women's Hospital in Boston, is working to identify a gene or genes underlying the development of focal glomerulosclerosis. Several studies have suggested that familial forms of FGS exist. The genes underlying these rare inherited forms of FGS may also be involved in the development of secondary FGS. Dr. Pollak is using a method called "positional cloning," to identify genes involved in inherited forms of FGS. His findings could ultimately lead to more effective diagnosis and treatment of patients with FGS.
Polycystic Kidney Disease
Polycystic Kidney Disease (PKD) is a leading inherited disorder in the United States. It affects more than 600,000 Americans, and leads to kidney failure in about 50 percent of patients by 60. Ongoing research continues to increase our understanding of the genetic basis of PKD. From this expanding knowledge, new therapies to prevent or treat the disease may soon be developed. Yoshiko Maeda, M.D., an NKF Research Fellow at Albert Einstein College of Medicine, Bronx, New York, is working with a newly discovered protein which is closely related to the protein that causes the adult form of PKD. Dr. Maeda's project is targeted at learning more about the structure of this protein, determining where it is located in the tissues and cell structure of the body, and investigating the possibility that this protein interacts directly with the PKD gene and also may be involved in other diseases related to PKD. Proof of this interaction could enhance our understanding of the causes of this disease and perhaps lead to improved treatments.
In 1997, the National Kidney Foundation launched its Dialysis Outcomes Quality Initiative (DOQItm), a ground-breaking major initiative researched and developed to improve quality of care and outcomes for dialysis patients. The Foundation continues to work toward the establishment of guidelines on nutrition in dialysis care, while currently making efforts to disseminate and implement DOQI's clinical guidelines on hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anemia. Additional recommendations continue to be made for research needs which may further improve outcomes for dialysis patients. NKF Research Fellow, Bertrand L. Jaber, M.D., of New England Medical Center in Boston, is addressing problems encountered in hemodialysis. In both reversible and permanent kidney failure, Dr. Jaber notes such complications as low blood pressure, heart disease, infection and decreased immunity. In an effort to improve long-term outcomes for dialysis patients, Dr. Jaber is examining the effects of two different artificial kidneys on outcomes of patients with reversible kidney failure; the long- term effects of dialysis dose and two different artificial kidneys on patients with permanent kidney failure, and the effects of exercise and a low protein diet on the immune system in ESRD. Douglas E. Mesler, M.D., an NKF Young Investigator at Boston University Medical Center, is carrying out analyses of such factors as: functional status, age, sex and race, and the development of casemix models which may help to answer research questions regarding dialysis patient-variables vs. dialysis outcomes.
Kidney transplantation is the preferred treatment choice for end-stage renal disease (ESRD) patients. However, even though transplantation is largely successful, and steadily improving post-transplant treatment regimens have increased the survival of transplants, chronic rejection of the new kidney nevertheless continues to present problems. Researchers are constantly working to better understand the rejection process and to find answers which will improve long-term outcomes.
James A. Evanson, M.D., an NKF Research Fellow at Vanderbilt University in Nashville, Tennessee, is investigating the relationship between post-transplant complications and rejection, and protein and calorie malnutrition. Since malnutrition is a recognized negative predictor for ESRD patient-outcomes across all treatment modalities, Dr. Evanson hypothesizes that kidney transplant patients who are well nourished should have fewer complications and better outcomes.
Using rat models, NKF Young Investigator, Daniel Shoskes, M.D., of Harbor-UCLA Medical Center in Torrance, California, is studying the possible positive effects of certain compounds called bioflavanoids on both non-immune kidney damage and rejection in post-transplant patients.
Other NKF researchers carrying out studies on kidney transplantation include: Mohamed H. Sayegh, M.D., an NKF Clinical Scientist at Brigham and Women's Hospital, Boston; NKF Research Fellow, Xian Chang Li, M.D., Ph.D., of Beth Israel Hospital in Boston; Eugenia Fedoseyeva, Ph.D., an NKF Research Fellow at the University of California in San Francisco; NKF Research Fellow, Lee Ann MacMillan-Crow, Ph.D., of the University of Alabama at Birmingham; Damir Matesic, M.D., an NKF Research Fellow at Case Western Reserve University in Cleveland; and Mehul Gandhi, M.B.B.S., M.D., an NKF Research Fellow at Standford University in California.
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