Specific variants of genes involved in inflammation and blood vessel constriction are strongly associated with kidney damage in patients undergoing major heart surgery, researchers at Duke University Medical Center have found.
While renal dysfunction after heart surgery is a common occurrence, until now researchers have been unable to predict with any certainty which patients – based on their personal and medical characteristics – are at the highest risk. The current analysis showed that patients with the particular genetic variants, or polymorphisms, have a collective two- to four-fold greater likelihood of suffering renal dysfunction after heart surgery.
This is important, the researchers said, since one out of every 12 patients who undergo heart surgery suffers serious kidney impairment. While most cases of this kidney injury are transient, up to two percent of patients will require kidney dialysis, with 60 percent of those patients dying before hospital discharge. Since more than 750,000 patients worldwide undergo heart surgery every year, the magnitude of the problem is large, the researchers said.
The results of the Duke analysis were published in the March, 2005 issue of the American Journal of Kidney Disease. The research was supported by the National Institutes of Health and the American Heart Association.
"If the results of our study are borne out in other populations, they should not only be useful for physicians as they counsel their patients who are undergoing heart surgery, but may also help physicians as they decide between medical or surgical treatments, based on a patient's unique characteristics and genetic make-up," said lead researcher Mark Stafford-Smith, M.D., Duke cardiothoracic anesthesiologist. "This new genetic information may also help facilitate individually tailored medical therapy designed to reduce renal injury and its subsequent medical problems."
For the study, the researchers followed 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.