Obesity and oxidative stress predict AKI after cardiac surgery

Abstract

Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m(2) [95% confidence interval, 4.3%-53.4%]; P=0.02). Baseline F(2)-isoprostane (P=0.04), intraoperative F(2)-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F(2)-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F(2)-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association.

Trial registration: ClinicalTrials.gov NCT00141778.

Figures

Figure 1.

For any given BMI, the intraoperative concentrations of F2-isoprostanes were higher in patients with AKI than those without AKI. Tick marks on the x- and y-axes represent patients, and the curves are smoothed estimates of the groups with and without AKI. The x-axis is truncated at the 5th and 95th patient percentiles and the y-axis at the 5th and 90th percentiles for ease of exposition.

Figure 2.

Regression models for theoretical causal relationships. Adjustment covariates (AKI risk factors) are not shown for ease of exposition. (A) β1,BMI captures the total effect of BMI on AKI. (B) Total effect of BMI on AKI separated into direct (independent of candidate pathway biomarker) and indirect (via biomarker) effects. β2,BMI captures the direct effect of BMI on AKI adjusted for biomarker, β2,Biomarker captures the direct effect of biomarker on AKI, and β3,BMI captures the direct effect of BMI on candidate pathway biomarker. The product of β3,BMI and β2,Biomarker captures the indirect effect of BMI on AKI that is mediated by that candidate pathway biomarker.