Response to Letter Regarding Article, “Risk Index for Perioperative Renal Dysfunction/Failure: Critical Dependence on Pulse Pressure Hypertension”
We thank Dr Augoustides for his interest regarding our study1 and are pleased to respond to his questions regarding the independent effects of use of perioperative aprotinin and preoperative ACE inhibitors (ACEI).
To assess the effect of aprotinin on our findings, we must realize certain limitations: (1) the analysis is post hoc, for our formal design for this question (2001) did not include aprotinin; and (2) such analysis would include only one half of our cohort (the derivation cohort), reducing the sample size by 2420 patients, and further reduction for multiple drugs/incomplete information would further decrease power. Because of these considerations, we did not include in our report the post hoc analyses given below; however, we are pleased to address Dr Augoustides’ questions, given these limitations.
Among 4801 patients in the study cohort, 29.4% received aprotinin, with no significant difference in aprotinin use found between the derivation and validation cohorts (28.2% and 30.6%, respectively, P=0.10). For the 2079 derivation cohort patients (2381 less 302 excluded for multiple drugs, etc), we found that aprotinin was an independent predictor for renal injury either without exposure to preoperative ACEI (OR, 2.94; 95% CI, 1.59 to 5.42; P<0.001) or with exposure (OR, 2.88; 95% CI, 1.56 to 5.32; P<0.001).
To test the interaction between preoperative ACEI use and aprotinin use for renal events, we performed stratified data analyses, finding no interaction. For patients not taking ACEI, the OR (95% CI) for aprotinin versus control was 2.44 (1.52 to 3.90), and for patients taking ACEI, it was 2.33 (1.59 to 3.41). The crude OR equaled 2.52 (95% CI, 1.87 to 3.38; P<0.001; Cochran-Mantel-Haenszel statistic for general association, P<0.001), and the adjusted OR equaled 2.37 (95% CI, 1.76 to 3.19), with the Breslow-Day test for homogeneity of the ORs indicating P=0.878. We therefore conclude that preoperative ACEI use is neither a modifier nor a confounder for the association between aprotinin use and postoperative renal composite. Regarding ACEI as a predictor, it failed to meet the retention criterion of our multivariable logistic regression stepwise-selection procedure for renal risk.
Finally, we note that our findings regarding the renal risk index are not inconsistent with the previously reported data referenced by Dr Augoustides2 and further demonstrate the critical role that preoperative pulse pressure plays in perioperative renal injury. We are grateful to have the opportunity to address Dr Augoustides’ valuable comments.
Source of Funding
This work was supported by a grant from the Ischemia Research and Education Foundation.
Dr Aronson receives consultant fees from pharmaceutical and device companies, none of which are addressed in this study. Dr Fontes received a research grant from IREF and honoraria from the Medicine Co. Dr Mangano has intellectual rights to adenosine-regulating agents, none of which are addressed in this study. The other authors report no conflicts.
Aronson S, Fontes ML, Miao Y, Mangano DT; for the Investigators of the Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation. Risk index for perioperative renal dysfunction/failure: critical dependence on pulse pressure hypertension. Circulation. 2007; 115: 733–742.