Copyright © 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. <zdoi;10.1097/ALN.0000000000002104> Anesthesiology, V 128 • No 4 710 April 2018 A CUTE kidney injury (AKI) after coronary artery bypass grafting (CABG) with extracorporeal circula- tion (ECC) occurs in approximately one third of patients in most institutions, including our own, 1 and leads to increased long- and short-term morbidity and mortality. 1 Te source for AKI in CABG is multifactorial, but renal ischemia– reperfusion injury induced by the use of ECC is at least part of the cause, 2,3 especially in the poorly oxygenated and metabolic active outer medulla. A suggested mechanism is induced mitochondrial damage through the opening of the mitochondrial permeability transition pore (mPTP) dur- ing reperfusion, leading to cell injury or death. 4,5 Animal What We Already Know about This Topic • Acute kidney injury is common after cardiac surgery with cardiopulmonary bypass • Animal studies suggest that cyclosporine may be protective What This Article Tells Us That Is New • In a double-blind trial, 154 cardiac surgical patients were randomly assigned to 2.5 mg/kg cyclosporine or placebo • Plasma cystatin C, a marker of renal injury, increased more in patients given cyclosporine • Cyclosporine does not reduce the risk of acute renal injury after cardiac surgery Copyright © 2018, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. Anesthesiology 2018; 128:710-7 ABSTRACT Background: Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortal- ity. One suggested cause for acute kidney injury is extracorporeal circulation–induced ischemia–reperfusion injury. In animal studies, cyclosporine has been shown to reduce ischemia–reperfusion injury in the kidneys. We hypothesized that administer- ing cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery. Methods: Te Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double- blind, randomized, placebo-controlled, single-center study. Te primary objective was to assess if cyclosporine could reduce acute kidney injury in patients undergoing coronary artery bypass grafting surgery with extracorporeal circulation. In the study, 154 patients with an estimated glomerular fltration rate of 15 to 90 ml · min –1 · 1.73 m –2 were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine or placebo intravenously before surgery. Te primary endpoint was relative plasma cystatin C changes from the preoperative day to postoperative day 3. Secondary endpoints included biomarkers of kidney, heart, and brain injury. Results: All enrolled patients were analyzed. Te cyclosporine group (136.4 ± 35.6%) showed a more pronounced increase from baseline plasma cystatin C to day 3 compared to placebo (115.9 ± 30.8%), diference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). Te same pat- tern was observed for the other renal markers. Te cyclosporine group had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk), I (injury), or F (failure; 31% vs. 8%, P < 0.001). Tere were no diferences in safety parameter distribution between groups. Conclusions: Administration of cyclosporine did not protect coronary artery bypass grafting patients from acute kidney injury. Instead, cyclosporine caused a decrease in renal function compared to placebo that resolved after 1 month. (ANESTHE- SIOLOGY 2018; 128:710-7) This article is featured in “This Month in Anesthesiology,” page 1A. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org). Submitted for publication July 26, 2017. Accepted for publication December 27, 2017. From the Departments of Anesthesiology and Intensive Care (P.E., A.D., E.G., B.B., C.M., A.E., L.A.) and Cardiothoracic Surgery (S.N., A.M., H.B.), Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden; the Department of Mitochondrial Medicine, Clinical Sciences, Lund University, Lund, Sweden (M.J.H., E.E.); the Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, Michigan (S.J.); the Van Andel Institute, Grand Rapids, Michigan (S.J.); and the Cardiovascular Institute, Stanford University, Stanford, California (S.J.). Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function A Randomized Clinical Trial Per Ederoth, M.D., Ph.D., Alain Dardashti, M.D., Ph.D., Edgars Grins, M.D., Björn Brondén, M.D., Ph.D., Carsten Metzsch, M.D., Ph.D., André Erdling, M.D., Shahab Nozohoor, M.D., Ph.D., Arash Mokhtari, M.D., Ph.D., Magnus J. Hansson, M.D., Ph.D., Eskil Elmér, M.D., Ph.D., Lars Algotsson, M.D., Ph.D., Stefan Jovinge, M.D., Ph.D., Henrik Bjursten, M.D., Ph.D. PERIOPERATIVE MEDICINE Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/128/4/710/488493/20180400_0-00013.pdf by guest on 12 June 2022