Contact

Duke Health News

919-660-1306

NEW ORLEANS -- Duke University Medical Center researchers
have uncovered an intriguing clue why one of every 12 patients
undergoing coronary artery bypass surgery suffers serious
kidney impairment, and they believe their findings provide a
target for new medications aimed at protecting kidneys.

The culprits, the researchers say, may be toxins that are
released into the bloodstream by bacteria residing in the
gastrointestinal tract in response to the surgery. These toxins
can cause inflammation in tissues throughout the body,
particularly the kidneys, where they appear to negatively
impact the kidneys' ability to filter blood.

"We found that patients who had higher levels of antibodies
circulating in their blood to neutralize or soak up these
toxins had much better kidney function after surgery," said
Duke anesthesiologist Dr. Mark Stafford-Smith. "With this
knowledge, we can now come up with an intervention that either
dampens the release of these toxins or increases the production
of the antibodies, or both." Stafford-Smith presented the
results of his team's study today (Oct. 16) during the annual
scientific sessions of the American Society of
Anesthesiologists.

More than 750,000 patients worldwide undergo bypass surgery
every year, and researchers estimate that about 8 percent of
those will suffer kidney damage after surgery. While most cases
of kidney damage are transient, up to 2 percent of patients
will require kidney dialysis. Additionally, 60 percent of those
requiring dialysis will die before hospital discharge,
Stafford-Smith said, highlighting the importance of kidney
protection in these patients.

The toxins in question, called endotoxins, come from a class
of bacteria known as gram-negative bacteria that reside in the
gut. The researchers believe the endotoxins are released in
response to the use of the heart-lung machine ? which
circulates the blood throughout the body while surgeons operate
on a stopped heart ? triggering a cascade of immunological
events leading to systemic inflammation, Stafford-Smith
explained.

The Duke investigators wanted to determine if the levels of
specific antibodies ? endotoxin core antibodies (IgM EndoCAb) ?
played a role in the kidney injuries. They already knew that
low levels of these antibodies corresponded to worse overall
outcomes after surgery, but no one had studied their effects on
kidney function.

To test their hypothesis, the researchers measured the
levels of the antibodies in the blood of 461 patients before
surgery and then correlated these levels with post-surgical
levels of creatinine, a byproduct of normal metabolism.

Kidneys normally filter creatinine out of the blood and
excrete it in the urine, so higher than normal levels in the
blood indicate that the kidneys' ability to filter blood has
been impaired. Patients were separated into two groups ? 182
patients with high levels and 279 patients with low levels of
antibodies in their blood.

"We found a statistically significant association between
low levels of the IgM EndoCAb levels and increased levels of
creatinine," Stafford-Smith said. "Those patients with more of
the antibodies in their blood appeared to have a greater level
of protection for their kidneys."

Specifically, the peak rise from baseline in creatinine
levels for those with high antibody levels was 20.9 percent,
while patients with low antibody levels saw peak creatinine
levels rise 31.3 percent. Additionally, this increase was
independent of other factors, such as age, gender and diabetes,
Stafford-Smith said.

"None of the medications designed to protect the kidneys of
surgery patients has been shown to be effective," said
Stafford-Smith. "Since kidney function after surgery is an
important determinant of outcome and quality of life, it is
important to come up with ways to protect the kidneys. We now
may have a target."

Such therapies could include drugs that modulate the immune
response, or even a vaccine that could be given before a
surgery to stimulate the production of IgM EndoCAbs, he
added.

"Even patients with minor kidney impairment after surgery
have higher rates of in-hospital complications, tend to remain
in intensive care units longer and will be discharged from the
hospital later," Stafford-Smith said. "Additionally, the
likelihood of these patients being discharged to an extended
care facility is up to three times higher than for patients
without kidney impairment."

The research was supported by Eisai, Inc., Teaneck, N.J., in
collaboration with Duke's Department of Anesthesiology.

Last year, Stafford-Smith's team was the first to
demonstrate a genetic link between heart surgery patients who
suffer kidney damage and those who don't. They found that a
gene variant (APOE-4), already implicated in the most common
form of Alzheimer's disease, appears to offer protection to the
kidney.

Members of Stafford-Smith's team are Duke colleagues Barbara
Phillips-Bute, Dr. Brian McCreath, Dr. Madhav Swaminatham and
Dr. Mark Newman.

###