It is in this vasoconstriction phenomenon where it appears that different polymorphisms may explain the increased kidney damage seen in AfricanAmericans, who if they possess two polymorphisms involved in vascular responsiveness endothelial nitric oxide synthase 849T and angiotensin converting enzyme deletion allele had a 162.5 percent increase in creatinine in the blood. This translates into a 60 percent reduction in the kidney's filtering ability, a rate more than twice as high as the study population as a whole.
"If this vulnerability is borne out in larger clinical trials, this would be a finding of great clinical significance," Stafford-Smith said. "The polymorphisms of these genes, since they are vital to controlling blood flow in the kidney, may contribute not only to the initial insult during low blood flow, but also throughout the recovery phase."
Some other polymorphisms also examined by the researchers showed smaller abilities to predict renal dysfunction after surgery. While these associations were weaker, Stafford-Smith said that the other polymorphisms, when combined with other factors, could still be relevant in predicting patients at risk.
Stafford-Smith added that there are likely other polymorphisms whether expressed individually or in combination with others that are involved in the kidney damage. Further studies are needed to confirm these findings in other populations, and to identify additional genetic factors, he added.
Other members of the team, all from Duke, are: Mihai Podgoreanu, M.D., Madhav Swaminatham, M.D., Barbara Phillips-Bute, Ph.D., Joseph Mathew, M.D., Elizabeth Hauser, Ph.D., Michelle Winn, M.D., Carmelo Milano, M.D., Dahlia Nielsen, Ph.D., Mike Smith, Richard Morris, Ph.D., Mark Newman, M.D., and Debra Schwinn, M.D. All are members of the Perioperative Genetics and Safety Outcomes Study (PEGASUS) team.
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Contact: Richard Merritt
Merri006@mc.duke.edu
919-684-4148
Duke University Medical Center
1-Mar-2005