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Effect of Remote Ischemic Preconditioning on Kidney Injury Among High-Risk Patients Undergoing Cardiac Surgery

Effect of Remote Ischemic Preconditioning on Kidney Injury Among High-Risk Patients Undergoing... ImportanceNo interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery. ObjectiveTo determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery. Design, Setting, and ParticipantsIn 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. InterventionsPatients 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. Main Outcomes and MeasuresThe 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. ResultsAcute 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 and RelevanceAmong 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. Trial RegistrationGerman Clinical Trials Register Identifier: DRKS00005333 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

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References (42)

Publisher
American Medical Association
Copyright
Copyright 2015 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2015.4189
pmid
26024502
Publisher site
See Article on Publisher Site

Abstract

ImportanceNo interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery. ObjectiveTo determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery. Design, Setting, and ParticipantsIn 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. InterventionsPatients 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. Main Outcomes and MeasuresThe 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. ResultsAcute 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 and RelevanceAmong 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. Trial RegistrationGerman Clinical Trials Register Identifier: DRKS00005333

Journal

JAMAAmerican Medical Association

Published: Jun 2, 2015

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