title: Does the combination of aprotinin and angiotensin-converting enzyme inhibitor cause renal failure after cardiac surgery?
abstract: BACKGROUND
  Aprotinin use in cardiac surgery has been associated with mild elevations in serum creatinine but generally has not been associated with an increase in the risk of acute renal failure. In the presence of angiotensin-converting enzyme (ACE) inhibitors, however, aprotinin may contribute to significant reductions in glomerular perfusion pressure. The purpose of this study was to test the hypothesis that the combination of ACE inhibitors and aprotinin cause renal failure after cardiac surgery.
  
  
  METHODS
  The study consisted of a retrospective investigation of all adult patients undergoing coronary artery bypass graft, valve, or combined procedures during the years 2000 to 2002 at a single institution. Aprotinin was administered selectively for reoperations, combined procedures, and other operations deemed to be at higher risk for bleeding. Excluded from analysis were patients with preoperative serum creatinine greater than 1.5 mg/dL, a history of renal failure, emergent or salvage procedures, preoperative use of intraaortic balloon pump, and off-pump procedures. Perioperative renal failure was defined as creatinine greater than 2.0 mg/dL within 72 hours of surgery. Preoperative demographic and intraoperative variables were analyzed with univariate and logistic regression analysis with odds ratio (OR) and bootstrap validation.
  
  
  RESULTS
  A total of 1,209 patients were included. The incidence of perioperative renal failure was 3.5%, and mortality in this group was 48%. Controlling for other demographic and intraoperative variables that may affect renal function (age, sex, diabetes mellitus, hypertension, New York Heart Association class, prior cardiac surgery, valve procedures, cardiopulmonary bypass time, aortic cross-clamp time, lowest hematocrit during cardiopulmonary bypass, transfusions) the preoperative use of ACE inhibitors along with intraoperative use of aprotinin was significantly associated with acute renal failure (OR 2.9, 95% confidence interval [CI]: 1.4 to 5.8, p < 0.0001). The effect of either drug alone was not significant. Other identified risk factors included age (OR 1.2 per year, CI: 1.01 to 1.5, p = 0.035), valve procedure (OR 2.7, CI: 1.3 to 5.7, p = 0.016), lowest hematocrit on cardiopulmonary bypass (OR 2.2, CI: 1.6 to 3.2, p < 0.0001), and transfusions of red blood cells (OR 1.04 per unit, CI: 1.02 to 1.06, p < 0.0001) and platelets (OR 1.7 per unit, CI: 1.2 to 2.4, p = 0.001).
  
  
  CONCLUSIONS
  The combination of preoperative use of ACE inhibitors and intraoperative use of aprotinin should be avoided in cardiac surgery.
authors.affiliation: Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. tkincaid@wfubmc.edu
authors.forename: Edward H
authors.initials: EH
authors.lastname: Kincaid
authors.forename: David A
authors.initials: DA
authors.lastname: Ashburn
authors.forename: John R
authors.initials: JR
authors.lastname: Hoyle
authors.forename: Marc G
authors.initials: MG
authors.lastname: Reichert
authors.forename: John W
authors.initials: JW
authors.lastname: Hammon
authors.forename: Neal D
authors.initials: ND
authors.lastname: Kon
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D000367:Age Factors; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D007611:Aprotinin / Q000009:adverse effects*; D006348:Cardiac Surgical Procedures / Q000706:statistics & numerical data; D015984:Causality; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006351:Heart Valves / Q000601:surgery; D006400:Hematocrit / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009657:North Carolina / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin