Biomarker warns of kidney injury in heart surgery patients

Heart surgeons may soon be able to identify within an hour of surgery which patients are at high risk for kidney injury, University of Florida College of Medicine researchers said today (Tuesday, Oct. 14) at the 2008 Clinical Congress of the American College of Surgeons in San Francisco.

Among medical concerns associated with complex heart surgery, kidney damage ranks only behind death, heart attack and stroke. Current blood tests warn of potential kidney problems within one or two days after heart surgery. UF surgeons believe developing a test that identifies at-risk patients while they are still in the operating room could lead to treatments that prevent kidney injury altogether.

In a retrospective study of patients who had complex heart surgery, UF researchers found a correlation between postsurgery kidney damage and the early presence of a protein called neutrophil-gelatinase-associated-lipocalin, or NGAL, in the blood. NGAL and other inflammatory biomarkers were detected as soon as one hour after completion of surgery, compared with the current test of serum creatinine, which does not show injury until one to two days later.

"The problem with kidney injury is that the markers we commonly use, like measuring the serum creatinine, often change when it is already too late in the game," said presenter Tad Kim, M.D., a UF surgical resident who is spending two years in the laboratory as part of his training. "The damage is already done and you can try to help rescue the kidneys, but you haven't really caught it early enough. It would be nice if we could see something via a simple blood or urine test that tells us earlier in the process that the kidneys are undergoing injury so we can intervene instead of waiting."

The UF study examined the results of 38 patients who underwent thoracic aorta or valve operations and found that after just one hour, the NGAL levels and inflammatory biomarkers were already elevated in those patients who developed postsurgery kidney injury.

The study's principal investigator, Thomas Beaver, M.D., an associate professor of thoracic and cardiovascular surgery, said 10 percent to 40 percent of patients undergoing heart surgery are at risk for some level of kidney injury. Kidney damage to the extent of requiring dialysis results in about 1 percent of standard cardiac operations and 8 percent of more complex aortic surgeries. However, researchers say even milder degrees of kidney injury have been associated with negative outcomes.

"The kidneys are sensitive and highly dependent on their blood supply, which can be impaired during and after surgery," Beaver said. "They get 20 percent of the body's blood flow, so any debris that is in the bloodstream at the time of surgery is at risk of reaching the kidneys."

He added that the drugs used during surgery and the heart-lung bypass machine itself also can be hard on the kidneys.

The development of a test that provides nearly instant results would be the first part of preventing kidney injury. The second part is the development of a therapeutic intervention. Currently there is no FDA-approved drug that can intervene and stop damage to the kidneys during surgery, but UF researchers are involved in two clinical trials evaluating drugs that may have protective value.

"What would be nice is if before the operation we can identify the higher-risk group based on current diseases, comorbidities, and type of surgery they are undergoing," Kim said. "If we thought that there were high enough risks for kidney injury, then we could justify using that compound (drug) in those patients."

Beaver said one of the UF clinical trials is examining whether an experimental compound called AP214 can reduce the inflammatory response after cardiac surgery and also reduce the levels of NGAL that are released.

He also said research is still in the early stages but perhaps within three years it will be possible to administer a test in the operating room, receive immediate feedback on signals of kidney injury, and then deliver drug intervention.

Titte Srinivas, M.D., an associate staff member in the department of nephrology and hypertension at the Cleveland Clinic's Glickman Urologic and Kidney Institute, said finding a biomarker to identify a subset of patients who may develop renal failure after cardiac surgery is important.

"Previous studies have looked at people after they have established kidney failure," Srinivas said. "The fact that the investigators were able to identify subjects before they manifest kidney failure is important in that it may help identify those patients who can be treated early and potentially help their clinical course."

He added that kidney failure contributes to mortality and health-care costs, so it would be helpful to be able to identify candidates for potential treatments aimed at preventing the onset of post-cardiac surgical renal failure or lessening its severity.