title: Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial.
abstract: OBJECTIVE
  No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery.
  
  
  OBJECTIVE
  To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery.
  
  
  METHODS
  In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle.
  
  
  METHODS
  Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation.
  
  
  METHODS
  The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers.
  
  
  RESULTS
  Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) (P = .04). There was no significant effect of remote ischemic preconditioning on myocardial infarction, stroke, or mortality. Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor-binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery (remote ischemic preconditioning, 0.36 vs control, 0.97 ng/mL2/1000; difference, 0.61; 95% CI, 0.27-0.86; P < .001). No adverse events were reported with remote ischemic preconditioning.
  
  
  CONCLUSIONS
  Among high-risk patients undergoing cardiac surgery, remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy. The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation.
  
  
  BACKGROUND
  German Clinical Trials Register Identifier: DRKS00005333.
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Wempe
authors.affiliation: Department of Cardiac Surgery, University of Münster, Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Martens
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Palliative and Pain Medicine, University Hospital Bochum, Bochum, Germany.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Zahn
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine, Palliative and Pain Medicine, University Hospital Bochum, Bochum, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Wolf
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Goebel
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: Christian I
authors.initials: CI
authors.lastname: Schwer
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rosenberger
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Helene
authors.initials: H
authors.lastname: Haeberle
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Görlich
authors.affiliation: Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.affiliation: Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, University Hospital Münster, Münster, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meersch
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000209:Acute-Phase Proteins / Q000652:urine; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D006348:Cardiac Surgical Procedures; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D019194:Ischemic Preconditioning; D007902:Length of Stay; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D011518:Proto-Oncogene Proteins / Q000652:urine; D017582:Renal Replacement Therapy / Q000706:statistics & numerical data
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine