Effects of aprotinin dosage on renal function: an analysis of 8,548 cardiac surgical patients treated with different dosages of aprotinin.
BACKGROUND
The nonspecific serine protease inhibitor aprotinin is widely used in cardiac surgery to limit bleeding. Recently, concerns about the safety of this drug were raised, especially regarding impaired renal outcome. This event rate was supposed to be dose dependent.


METHODS
In this observational study, the authors analyzed prospectively collected data of a single-center cardiac-anesthetic database. Adult patients treated with various dosages of aprotinin were evaluated. Logistic regression analysis identified independent predictors of renal outcome. The primary endpoint was a composite of novel postoperative renal failure requiring hemodialysis, an increased postoperative creatinine plasma concentration of 2 mg/dl or greater, or a difference between maximal postoperative and preoperative plasma creatinine of 0.7 mg/dl or greater.


RESULTS
The study analyzed 8,548 patients. Multiple logistic regression (c index = 0.861) did not show a significant association between aprotinin dosage and renal outcome, as did the bootstrap procedure (odds ratio, 0.98; confidence interval, 0.90-1.07). The most relevant predictor was a preoperatively elevated creatinine concentration (odds ratio, 11.4; confidence interval, 9.05-14.3). Patients with postoperative renal impairment or failure were at higher preoperative risk and/or underwent more complex procedures. In subgroups of patients with preoperatively impaired renal function (creatinine > or =1.5 mg/dl) (n = 1,075), complex procedures (n = 1,920), or insulin-dependent diabetes (n = 650) or patients undergoing isolated myocardial revascularization (n = 4,901), no association between aprotinin dosage and adverse renal outcome was observed.


CONCLUSIONS
In the current analysis, aprotinin dosage was not associated with increased adverse renal outcome. In regard to renal outcome, this analysis did not demonstrate an essential detrimental influence of aprotinin dosage on renal function.
Dietrich
Wulf
W
Institute for Research in Cardiac Anesthesia, Munich, Germany. wulf.dietrich@t-online.de
Busley
Raimund
R
Boulesteix
Anne-Laure
AL
D007611:Aprotinin / Q000627:therapeutic use*; D006348:Cardiac Surgical Procedures / Q000145:classification*; D001026:Coronary Artery Bypass / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005858:Germany; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D007677:Kidney Function Tests; D015999:Multivariate Analysis; D012044:Regression Analysis; D012189:Retrospective Studies; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
D006490:Hemostatics; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin