**5. Conclusions**

In the setting of cardiac surgery, we identified the *MIF* promotor polymorphisms CATT7 (rs3063368) and -270 (formerly -173) G>C (rs755622), to be predictive of development of postoperative AKI and death. These *MIF* promoter alleles could improve current clinical risk prediction models and thus serve as a helpful decision-making tool for clinicians and patients in the near future.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2077-0383/9/9/2936/s1. Supplemental Figure S1. Flowchart of the patients screened and included in the study. Supplemental Figure S2. SNP rs5844572 region (CATTn tetranucleotide repeat) and rs755622 (G>C) with UCSC genome browser (Geb. 2009; GRCh37/hg19 Assembly). Supplemental Table S1. Primer sequences used for genotyping of the tetranucleotide repeat polymorphism CATTn (rs3063368). Supplemental Table S2. Association of *MIF* promoter polymorphisms with Myocardial Infarction. Supplemental Table S3. Association of *MIF* promoter polymorphisms with Stroke. Supplemental Table S4. Association of *MIF* promoter polymorphisms with delir. Supplemental Table S5. Association of MIF regulatory polymorphisms with atrial fibrillation.

**Author Contributions:** Conceptualization, L.A., C.S. and K.Z.; Methodology, L.A., C.S., K.F.; Software, K.F., C.S.; Validation, K.F., L.A., C.S., Formal Analysis, K.F., L.A., C.S., J.B.; Investigation, L.A., K.F., S.M., C.S.; Resources, C.S., K.Z., R.B., J.B., G.M.; Data Curation, K.F., L.A.; Writing—Original Draft Preparation, L.A., C.S.; Writing—Review and Editing, J.B., R.B., H.S., H.-J.L., S.M., P.M., D.W., L.L., G.M., D.E.L., A.Z.; Project Administration, C.S.; Funding Acquisition, C.S., K.Z., J.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** This study was partly supported by the Deutsche Forschungsgemeinschaft (DFG; STO 1099/8-1 to CS BE 1977/9-1; BE 1977/14-1 to JB; SFB1123/A3 to JB). The RIPHeart Study was funded by the German Research Foundation (ME 3559/1-1).

**Acknowledgments:** We are thankful for the technical support received from Christian Beckers. RIPHeart Study Collaborators: Ana Stevanovic, Rolf Rossaint, Marc Felzen, Andreas Goetzenich, Tobias Moormann, Katharina Chalk, Pascal Knuefermann, Thomas Recht, Andreas Hoeft, Michael Winterhalter, Sonja Iken, Carolin Wiedenbeck, Gerhard Schwarzmann, Simone Lindau, Andreas Zierer, Stephan Fichtlscherer, Gerold Goerlach, Matthias Wollbrueck, Ursula Boening, Markus Weigand, Julia Strauchmann, Kai U. Morsbach, Markus Paxian, Konrad Reinhard, Jens Scholz, Jochen Renner, Ole Broch, Helga Francksen, Bernd Kuhr, Hermann Heinze, Hauke Paarmann, Hans-Hinrich Sievers, Stefan Klotz, Thomas Hachenberg, Christian Werner, Susanne Mauff, Angela Alms, Stefan Bergt, and Norbert Roewer. Aachen (Department of Anesthesiology, Medical Faculty RWTH Aachen University, Aachen, Germany): Ana Stevanovic, Rolf Rossaint, Marc Felzen, (Department of Thoracic and Cardiovascular Surgery): Andreas Goetzenich; 195 patients; Berlin (Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany): Tobias Moormann, Katharina Chalk; 37 patients; Bonn (Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany): Pascal Knuefermann, Thomas Recht, Andreas Hoeft; 73 patients; Duesseldorf (Department of Anesthesiology and Intensive Care Medicine, University Hospital Duesseldorf, Germany): Michael Winterhalter; 65 patients; Frankfurt am Main (Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany): Sonja Iken, Carolin Wiedenbeck, Gerhard Schwarzmann, Simone Lindau, (Department of Thoracic and Cardiovascular Surgery): Andreas Zierer, (Internal Medicine III: Cardiology, Angiology, Nephrology): Stephan Fichtlscherer; 117 patients; Giessen (Department of Cardiovascular Surgery, University of Giessen, Germany): Gerold Goerlach, Matthias Wollbrueck, Ursula Boening; (Department of Anesthesiology): Markus Weigand; 148 patients; Goettingen (Department of Anesthesiology and Intensive Care Medicine, University Hospital Goettingen, Germany): Julia Strauchmann, Konrad August; 91 patients; Jena (Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany): Kai U. Morsbach, Markus Paxian, Konrad Reinhard; 76 patients; Kiel (Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany): Jens Scholz, Jochen Renner, Ole Broch, Helga Francksen, Bernd Kuhr; 237 patients; Luebeck (Department of Anesthesiology, University Hospital Luebeck, Luebeck, Germany): Hermann Heinze, Hauke Paarmann; (Department of Cardiac and Thoracic Vascular Surgery): Hans-Hinrich Sievers, Stefan Klotz; 56 patients; Magdeburg (Department of Anesthesiology, University Hospital Magdeburg, Germany); Thomas Hachenberg; 14 patients; Mainz (Department of Anesthesiology, Medical Center of Johannes Gutenberg-University, Mainz, Germany): Christian Werner, Susanne Mau ff; 116 patients; Rostock (Clinic of Anesthesiology and Intensive Care Medicine, University Hospital Rostock, Rostock, Germany): Angela Alms, Stefan Bergt; 146 patients; Wuerzburg (Department of Anesthesiology, University Hospital Wuerzburg, Wuerzburg, Germany): Norbert Roewer; 32 patients.

**Conflicts of Interest:** R.B. has significant financial interests. He is a co-inventor on patents related to therapeutic MIF modulation and MIF genotyping, and owns more than 5% of the voting shares in MIFCOR, Inc, a Yale University biotechnology start-up company. J.B. is a co-inventor on patents describing the therapeutic utility of MIF antagonists (modest interests). D.E.L. has received research gran<sup>t</sup> support from BioPorto Diagnostics (modest interests). R.B., J.B., and D.E.L. did not shape or manipulate the design and execution of the study. They contributed by helping with interpretation of data and by reviewing the manuscript.
