Abstract
Background: Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5–7 (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Methods: In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40–2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99–33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20–2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46–3.09), p < 0.001) and death (OR 5.58 (1.29–24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.
Highlights
Conventional open-heart surgery is performed annually in more than one million patients worldwide, and the incidence of postoperative sequelae including acute organ dysfunction remains high [1,2]
The present study is a predefined sub-study performed in cardiac surgery patients of the Remote Ischemic Preconditioning Heart (RIPHeart) study (January 2011–May 2014), which investigated whether upper limb remote ischemic conditioning reduced mortality and the incidence of myocardial infarction, stroke, and acute kidney injury (AKI) in adults scheduled for elective cardiac surgery requiring a cardiopulmonary bypass [13]
Postoperative AKI was associated with older age (p < 0.001), female gender (p = 0.007), the intake of aspirin (p = 0.01), lower baseline hemoglobin (
Summary
Conventional open-heart surgery is performed annually in more than one million patients worldwide, and the incidence of postoperative sequelae including acute organ dysfunction remains high [1,2]. While clinical scoring systems such as the well-established EuroSCORE were primarily developed for the preoperative risk stratification of mortality in cardiac surgery patients, only limited evidence exists about its value for postoperative organ dysfunction and other complications [3]. We analyzed whether MIF promoter polymorphisms impact the risk of postoperative organ dysfunction and mortality in patients undergoing cardiac surgery. The aim of this study was to analyze whether the polymorphisms CATT5–7 (rs5844572/rs3063368,“-794”) and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. Results: Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs 13%; OR 2.01 (1.40–2.88), p = 0.0001). Conclusion: The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance
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