Acute kidney injury (AKI) is common after major abdominal surgery. Selection of candidate kidney protective strategies for testing in large trials should be based on robust preliminary evidence.


A secondary analysis of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial was conducted in adult patients undergoing major abdominal surgery and randomly assigned to a restrictive or liberal perioperative fluid regimen. The primary outcome was maximum AKI stage before hospital discharge. Two multivariable ordinal regression models were developed to test the primary hypothesis that modifiable risk factors associated with increased maximum stage of postoperative AKI could be identified. Each model used a separate approach to variable selection to assess the sensitivity of the findings to modeling approach. For model 1, variable selection was informed by investigator opinion; for model 2, the Least Absolute Shrinkage and Selection Operator (LASSO) technique was used to develop a data-driven model from available variables.


Of 2,444 patients analyzed, stage 1, 2, and 3 AKI occurred in 223 (9.1%), 59 (2.4%), and 36 (1.5%) patients, respectively. In multivariable modeling by model 1, administration of a nonsteroidal anti-inflammatory drug or cyclooxygenase-2 inhibitor, intraoperatively only (odds ratio, 1.77 [99% CI, 1.11 to 2.82]), and preoperative day-of-surgery administration of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker compared to no regular use (odds ratio, 1.84 [99% CI, 1.15 to 2.94]) were associated with increased odds for greater maximum stage AKI. These results were unchanged in model 2, with the additional finding of an inverse association between nadir hemoglobin concentration on postoperative day 1 and greater maximum stage AKI.


Avoiding intraoperative nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors is a potential strategy to mitigate the risk for postoperative AKI. The findings strengthen the rationale for a clinical trial comprehensively testing the risk–benefit ratio of these drugs in the perioperative period.

Editor’s Perspective
What We Already Know about This Topic
  • The literature regarding nonsteroidal anti-inflammatory drug/cyclooxygenase-2 inhibitor use in the perioperative setting is mixed with regard to whether there is a significant association between perioperative nonsteroidal anti-inflammatory drug/cyclooxygenase-2 inhibitor use and increased occurrence of acute kidney injury after noncardiac surgery
  • This is concerning because some Enhanced Recovery After Surgery protocols include administration of nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors despite uncertainty about whether nonsteroidal anti-inflammatory drugs/cyclooxygenase-2 inhibitors are associated with increased postoperative acute kidney injury in noncardiac surgical patients
What This Article Tells Us That Is New
  • This study focused on assessment of modifiable perioperative risk factors for developing postoperative acute kidney injury in patients undergoing major abdominal surgery and found that nonsteroidal anti-inflammatory drug/cyclooxygenase-2 inhibitor use, intraoperatively only, was significantly associated with increased postoperative acute kidney injury
  • This study and others in the literature support the need for a randomized trial of perioperative nonsteroidal anti-inflammatory drug/cyclooxygenase-2 inhibitors to better define the risk–benefit balance of these perioperative analgesic adjuncts