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Duke researchers uncover genetic link to kidney damage after heart surgery

ed 1,671 patients who underwent heart surgery at Duke University Hospital. Prior to surgery, the researchers performed genetic analysis of blood samples paying particular attention to 12 candidate polymorphisms on seven genes. These target genes were chosen because earlier studies suggested that they may play a role in kidney injury.

To determine kidney damage, the researchers measured the levels of creatinine, a normal byproduct of metabolism, in the blood after surgery. Higher-than-normal blood levels of creatinine indicate an impairment in the kidney's ability to filter, because kidneys normally filter creatinine out of the blood and excrete it in the urine. Typically, creatinine levels peak two days after surgery and return to normal by day five.

The researchers then correlated the individual polymorphisms with the peak levels of creatinine measured after surgery. Since race has already been determined to be an important independent predictor of kidney damage after surgery, the researchers performed separate analyses of Caucasians and African-Americans.

In Caucasians, the researchers found that patients having two polymorphisms involved in the inflammatory response angiotensinogen 842C and interleukin 6-572C had on average an 121 percent increase in creatinine, which is equivalent to a 55 percent reduction in the kidney's ability to filter waste. This rate was four times higher than the study population as a whole.

"This combination of the polymorphisms, which is present in about 6 percent of all Caucasians, is related to the effects which are seen in the kidneys - which we speculate are due to an amplified immune system inflammatory response to the surgery," Stafford-Smith said.

While the very act of surgery stimulates an immune system response, it has also been shown to cause blood vessel constriction, especially in the kidneys, Stafford-Smith continued. During these periods of constriction, the kidney's supply of ox
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Contact: Richard Merritt
Merri006@mc.duke.edu
919-684-4148
Duke University Medical Center
1-Mar-2005


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