Newly Published
Perioperative Medicine  |   January 2018
Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function: A Randomized Clinical Trial
Author Notes
  • 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.).
  • 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).
    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.
    Submitted for publication July 26, 2017. Accepted for publication December 27, 2017.×
  • Research Support: This work was supported by the Swedish Heart-Lung Foundation grant No. 86601 and Swedish ALF grants. NeuroVive Pharmaceutical AB, Lund, Sweden, provided the study treatment CicloMulsion and its placebo together with unrestricted research grants covering costs for the research nurses.
    Research Support: This work was supported by the Swedish Heart-Lung Foundation grant No. 86601 and Swedish ALF grants. NeuroVive Pharmaceutical AB, Lund, Sweden, provided the study treatment CicloMulsion and its placebo together with unrestricted research grants covering costs for the research nurses.×
  • Competing Interests: Dr. Ederoth has received lecture fees from Orion Pharma AB (Danderyd, Sweden). Drs. Hansson and Elmér are employed by and are shareholders of NeuroVive Pharmaceutical AB, Lund, Sweden. The other authors declare no competing interests. Financial support for research staff, laboratory tests, and the study drug was granted by NeuroVive Pharmaceutical AB. NeuroVive Pharmaceutical AB was given the opportunity to comment on the drafting of both the protocol and the manuscript, but the final decision on the study design was made solely by the investigators. Data were analyzed according to the statistical analysis plan by an independent external statistician (Clinical Studies Sweden, Forum South, Lund, Sweden). The authors designed the trial, gathered the data, supervised statistical analysis, prepared the manuscript, made the decision to submit the manuscript for publication, and vouch for the accuracy and completeness of the data set and adherence of the study to the protocol.
    Competing Interests: Dr. Ederoth has received lecture fees from Orion Pharma AB (Danderyd, Sweden). Drs. Hansson and Elmér are employed by and are shareholders of NeuroVive Pharmaceutical AB, Lund, Sweden. The other authors declare no competing interests. Financial support for research staff, laboratory tests, and the study drug was granted by NeuroVive Pharmaceutical AB. NeuroVive Pharmaceutical AB was given the opportunity to comment on the drafting of both the protocol and the manuscript, but the final decision on the study design was made solely by the investigators. Data were analyzed according to the statistical analysis plan by an independent external statistician (Clinical Studies Sweden, Forum South, Lund, Sweden). The authors designed the trial, gathered the data, supervised statistical analysis, prepared the manuscript, made the decision to submit the manuscript for publication, and vouch for the accuracy and completeness of the data set and adherence of the study to the protocol.×
  • Reproducible Science: Full protocol available at: henrik.bjursten@med.lu.se. Raw data available at: henrik.bjursten@med.lu.se.
    Reproducible Science: Full protocol available at: henrik.bjursten@med.lu.se. Raw data available at: henrik.bjursten@med.lu.se.×
  • Correspondence: Address correspondence to Dr. Bjursten: Department of Cardiothoracic Surgery, Clinical Sciences, Lund University, Skåne University Hospital, 221 85 Lund, Sweden. henrik.bjursten@med.lu.se. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Cardiovascular Anesthesia / Renal and Urinary Systems / Electrolyte Balance
Perioperative Medicine   |   January 2018
Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function: A Randomized Clinical Trial
Anesthesiology Newly Published on January 24, 2018. doi:10.1097/ALN.0000000000002104
Anesthesiology Newly Published on January 24, 2018. doi:10.1097/ALN.0000000000002104
Abstract

Background: Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortality. 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 administering cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery.

Methods: The Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized, placebo-controlled, single-center study. The 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 filtration 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. The 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. The 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%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). The same pattern was observed for the other renal markers. The 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). There were no differences 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.