Scientists led by a UC kidney expert have
found that a naturally occurring protein that normally fights cancer
cells can also cause severe kidney failure when normal blood flow is
This finding, seen in mice in which the
gene controlling the protein is actually expressed or "turned on,"
could provide a target for drugs that will reduce the risk of kidney
damage in humans, the researchers believe.
Acute kidney failure is a life-threatening illness caused by sudden, severe loss of blood flow to the kidneys (ischemia).
Common occurrences such as dehydration, a
car accident and blood infection, or more severe injuries such as those
suffered on the battlefield or during an earthquake, can compromise the
flow of blood to kidneys and result in acute kidney failure.
Despite advances in supportive care, such
as dialysis, severe kidney injury is a major cause of death. Many
patients with acute kidney failure also progress to chronic kidney
failure, which has only two treatment options--dialysis or kidney
Today, 240 people are on the kidney
transplant waiting list in Greater Cincinnati. Many wait up to five
years to receive a kidney.
The scientists, headed by Manoocher
Soleimani, MD, director of nephrology and hypertension at UC and the
Cincinnati Veterans Affairs Medical Center, report their findings in
the Dec. 1, 2005, issue of the Journal of Clinical Investigation.
The protein, thrombospondin (TSP-1), is
known for its role in fighting cancer. It does this by killing off
cancer cells and preventing the tumor from building a greater blood
Although TSP-1 causes irreversible,
severe kidney damage when blood flow to mouse kidneys is disrupted, the
researchers say, this only occurs in animals whose TSP-1 gene is turned
The study showed that the protein damages
kidney cells when blood flow is reduced for 30 minutes or more. When
blood flow is restored to the kidneys, if TSP-1 protein is present,
normal kidney function doesn't return.
"This raises the important possibility
that TSP-1 may serve as a target in preventing or successfully treating
acute kidney failure," says Dr. Soleimani. "Understanding the
mechanisms of kidney cell injury moves us that much closer to
preventing this life-altering damage from happening.
"If we can develop a drug that will
inhibit or turn off the TSP-1 gene function, then severe kidney damage
could be prevented--even during a 30-minute disruption in blood flow,"
"Since the incidence of death remains
high in patients with damaged kidneys, prevention or early treatment of
acute kidney failure will increase survival."
The study showed that the damaging
protein is released rapidly, in response to diminished blood flow, in
mice that have the active TSP-1 gene. TSP-1 also killed kidney cells
when exposed to them in a Petri dish.
"Most importantly," Dr. Soleimani says,
"we found that genetically engineered mice, which lack TSP-1 protein,
were significantly protected from kidney damage. Mice without TSP-1
preserved their kidney function relatively well, even after being
subjected to a 30-minute disruption of blood flow to the kidneys.
"Consequently, this study raises an
important possibility that TSP-1 may serve as a target for preventing
or successfully treating acute kidney failure," Dr. Soleimani adds.