title: 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.
authors.affiliation: Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. frederic.t.billings@vanderbilt.edu
authors.forename: Frederic T
authors.initials: FT
authors.lastname: Billings
authors.forename: Mias
authors.initials: M
authors.lastname: Pretorius
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Schildcrout
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Mercaldo
authors.forename: John G
authors.initials: JG
authors.lastname: Byrne
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D006348:Cardiac Surgical Procedures; D004232:Diuretics / Q000494:pharmacology; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011183:Postoperative Complications; D017257:Ramipril / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D004232:Diuretics; D028441:F2-Isoprostanes; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D013148:Spironolactone; D017257:Ramipril