In patients undergoing noncardiac surgery, neither aspirin nor clonidine (a medication primarily used to treat high blood pressure) taken before and after surgery reduced the risk of acute kidney injury, according to a study appearing in JAMA. The study is being released to coincide with its presentation at the American Society of Nephrology's annual Kidney Week meeting.
About 10 percent of the 200 million adults estimated to undergo major noncardiac surgery each year develop acute kidney injury (a sudden loss of kidney function). Perioperative (around the time of surgery) acute kidney injury is associated with poor outcomes, a long hospital stay, and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however these effects are uncertain and each intervention has the potential for harm (bleeding with aspirin and abnormally low blood pressure with clonidine), which could increase the risk of acute kidney injury, according to background information in the article.
Amit X. Garg, M.D., Ph.D., of the London Health Sciences Centre and Western University, London, Ontario, Canada, and colleagues randomly assigned 6,905 patients undergoing noncardiac surgery from 88 centers in 22 countries to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery; oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (applied to the skin) or placebo patch that remained until 72 hours after surgery. Acute kidney injury was primarily defined as a certain increase in serum creatinine concentration (a substance commonly found in blood, urine, and muscle tissue and used as an indicator of kidney function).
The researchers found that neither aspirin nor clonidine reduced the risk of acute kidney injury. The percentage of patients in each study group who experienced acute kidney injury: aspirin 13.4 percent vs 12.3 percent (placebo); clonidine 13.0 percent vs 12.7 percent (placebo).
Aspirin increased the risk of major bleeding. In turn, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3 percent when bleeding was present vs 12.3 percent when bleeding was absent). Similarly, clonidine increased the risk of clinically important hypotension (abnormally low blood pressure). Such hypotension was associated with a greater risk of subsequent acute kidney injury (14.3 percent when hypotension was present vs 11.8 percent when hypotension was absent).
The authors write that future large trials to prevent acute kidney injury in the surgical setting should focus on interventions that target pathways other than inhibiting platelet aggregation and alpha 2-adrenergic agonism. "Interventions that prevent perioperative bleeding and perioperative hypotension may prove useful."
(doi:10.1001/jama.2014.15284; Available pre-embargo to the media at http://media.
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Prevention of Acute Kidney Injury Using Vasoactive or Antiplatelet Treatment
Wolfgang C. Winkelmayer, M.D., M.P.H., Sc.D., of the Baylor College of Medicine, Houston, and Associate Editor, JAMA, and Kevin W. Finkel, M.D., of the University of Texas Medical School, Houston, comment on this study in an accompanying editorial.
"In their contribution, Garg and colleagues once again have embarked on a promising mechanism to generate evidence for kidney outcomes, which involved partnering with investigators of large cardiovascular trials and proposing (and then executing) ancillary studies of kidney-relevant end points. Given the disproportionate paucity of randomized trials in nephrology, this is a useful and economical approach, especially in light of the many risk factors that cardiovascular disease and both acute and chronic kidney disease share. It is almost unfathomable that funding agencies would have funded a stand-alone trial of interventions for the primary prevention of acute kidney injury of the size and scope of [this study]."
(doi:10.1001/jama.2014.14548; Available pre-embargo to the media at http://media.
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.