Obesity linked to kidney injury after heart surgery
A new study by Vanderbilt researchers finds that obesity markedly increases the risk of acute kidney injury (AKI) following cardiac surgery.
Considered common after cardiac surgery, AKI independently predicts a fivefold increase in mortality (within 30 days after cardiac surgery), and is associated with longer hospital stays and a range of complications.
Frederic T. (Josh) Billings IV, M.D., M.Sc.
The study, led by anesthesiologist Frederic T. (Josh) Billings IV, M.D., M.Sc., also digs deeper to examine suspected mechanisms by which obesity might influence AKI. Employing a statistical technique called mediation analysis, the study suggests that obesity influences AKI risk via oxidative stress.
Posing damage to cell structures, oxidative stress is the toxic overabundance of reactive oxygen species, brought on by excess generation or insufficient elimination.
“By identification of this mechanism, we now may be able to target intraoperative oxidative stress with the hope of reducing kidney injury following cardiac surgery. That may be particularly appropriate for obese individuals,” Billings said.
The study, appearing in an upcoming issue of the Journal of the American Society of Nephrology (and now posted on the society’s website), follows a sample of 455 cardiac surgery patients at Vanderbilt University Hospital and Brigham and Women’s Hospital in Boston. Some 25 percent of the patients developed AKI after their procedure.
To appreciate the magnitude of risk that was detected in the study, consider that a body mass index of 18.5 to 24.9 is considered normal, 25.0 to 29.9 is considered overweight and 30.0 to 34.9 is considered obese.
After adjusting for several other risk factors, the researchers found that for every five-point increase in BMI, the odds of AKI increased 26.5 percent.
In other words, compared to people in the normal range with a BMI of, say, 22, otherwise comparable but overweight people with a BMI of 27 have 26.5 percent greater odds of AKI after cardiac surgery, obese people with a BMI of 32 have 60 percent greater odds, severely obese people with a BMI of 37 have 102 percent greater odds, and so on through morbid obesity and super obesity.
To learn more, the researchers turned their attention to three molecular processes considered as separate suspected pathways by which obesity might influence AKI: inflammation; oxidative stress; and antifibrinolysis (abnormal blood clotting). They used a set of biomarkers to measure the effect of obesity on these three processes and, in turn, to measure the effects of these three processes on AKI risk.
“The careful deconstruction of the total effect of BMI on AKI into the direct effects of BMI on AKI and the indirect effects via biomarker pathways is the statistical beauty of the study,” Billings said.
Despite their association with AKI, there was little to no evidence to suggest that inflammation or antifibrinlysis were intermediaries between obesity and AKI.
Oxidative stress, however, loomed as a mediator between obesity and AKI risk. The authors write that the finding is “consistent with the hypothesis that oxidative stress partially mediates the association between BMI and AKI.”
“I think we learned something really important by doing the mediation analysis,” said biostatistician Jonathan Schildcrout, Ph.D., one of the study’s authors. “You could have just examined the BMI and AKI association, and everybody would have said, ‘OK, obese people have higher risk of AKI.’
“But what are you going to do about it? There’s nothing to do except tell people to lose weight. When you learn the mechanism, you can start to learn how to intervene to prevent the injury,” Schildcrout said.
The study was funded by the National Institutes of Health (RO1HL77389, RO1HL65193, and UL1RR024975). Clinical Trial Registration: NCT00141778.