Researchers at Duke have identified a possible cause of serious kidney damage after major heart surgery.
One in 12 patients who have had coronary artery bypass surgery experiences significant kidney failure.
Lead investigator Dr. Mark Stafford-Smith believes renal damage is caused by inflammatory responses resulting from major surgery. When the body is exposed to surgical machinery, heart valves become "leaky" and allow a bacterium called endotoxin to be released from the gastrointestinal tract into the body. This produces an inflammatory response believed to be involved in damage to various tissues, including the kidney.
To test whether endotoxin is responsible for triggering post-surgery inflammation, researchers obtained blood samples from 461 surgery patients and screened them for levels of endotoxin antibodies before their procedures.
"We hypothesized that if you have high levels of endotoxin antibodies, you could intercept the inflammatory response and would be less likely to experience renal problems," said Stafford-Smith, the interim chief of the division of cardiothoracic anesthesia.
After reviewing the data, the scientists found that higher levels of antibody concentration in the blood are associated with a lower risk of complications after surgery. These results were presented two weeks ago at a meeting of the American Society of Anesthesiologists.
"I think the findings are most important because they draw additional attention to endotoxin being a likely cause of kidney damage, which will hopefully further encourage development of appropriate anti-endotoxin strategies," said Dr. Elliott Bennett-Guerrero, chief of cardiothoracic anesthesiology at the Columbia University College of Physicians and Surgeons.
Researchers are now focusing their efforts on developing vaccines that will increase endotoxin antibody levels and drugs that will either block endotoxin levels or reduce the inflammatory response caused by the bacteria. "Our findings provide us with a new target to potentially use for treatment," said Stafford-Smith.
Anti-inflammatory drugs in preclinical and clinical trials are currently available, but scientists say they have not been successful. "It's likely many [of these drugs] failed because patients were being treated too late," said Bennett-Guerrero.
Over the past three decades, researchers have been concerned about post-surgical complications.
"People have been recognizing that kidney injury after surgery has been a significant problem, and that the rate of that problem hasn't changed much," said Stafford-Smith. "Every year, 1 or 2 percent [of bypass surgery patients] will have to have dialysis, and 10 percent will have moderate renal injury."
Anti-endotoxin therapies may therefore be significant for major surgery patients in the future.
"The endotoxin core antibodies can counteract the effects of the endotoxins, but some people seem to produce fewer antibodies than others," said Dr. Barbara Phillips-Bute, a senior research associate in the Department of Anesthesia. "Since kidney damage is still one of the bigger risks of cardiac surgery, these potential treatments could make a difference in the quality of surgical outcomes for heart patients."
Stafford-Smith is currently working on additional research to understand the role of genetics in post-surgical renal damage.
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