Letter by Augoustides Regarding Article “Aprotinin Does Not Increase the Risk of Renal Failure in Cardiac Surgery Patients”
To the Editor:
I read with great interest the excellent article by Furnary and colleagues1 detailing an analysis of aprotinin and acute dialysis-dependent renal failure in cardiac surgery patients. Their multivariate analysis has demonstrated that increasing perioperative red blood cell transfusion, rather than aprotinin, is an independent risk factor for acute renal failure after cardiac surgery.
The data analysis as presented, however, does not account for angiotensin blockade in the presence of aprotinin, a described significant risk factor for perioperative renal injury.2 Consequently, if a significant percentage of the aprotinin cohort were exposed to angiotensin-converting enzyme inhibition, it might confound the results of the multivariate analysis. If the data for this variable are readily available, it would be interesting see if this potential confounder could have had any significant statistical effect.
Furthermore, the authors state in their discussion that meta-analysis of randomized trials does not support a nephrotoxic association with aprotinin.3 However, very recent comprehensive meta-analysis has described a significant association between high-dose aprotinin and renal dysfunction after cardiac surgery.4 Thus, just as in red blood cell transfusion, the nephrotoxic effects of aprotinin may be dose-dependent.1–4
Consequently, it would be valuable to know whether aprotinin exposure in this study1 was treated as a categorical (yes/no) variable with disregard to the actual dosage regimen. If so, then the impact of aprotinin dosage as a confounder will be impossible to assess. If, however, dose discrimination is possible in the database, it would be reasonably apparent whether this confounder had a significant role in the study.
I congratulate the authors on a most thought-provoking study. I look forward to their analysis of these 2 confounders. I have no doubt that it will assist us in better understanding the predictors for acute renal failure in cardiac surgery.
Sources of Funding
This work was supported by the Department of Anesthesiology and Critical Care, Hospital of the University of Pennsylvania.