Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies

Frédérick D’Aragon, MD; William Rousseau, MD; Ruth Breau, BA; Daniel Aminaei, BSc; Carole Ichai, MD; Gordon J. Boyd, MD, PhD; Karen E. A. Burns, MD; Héloïse Cardinal, MD, PhD; François-Martin Carrier, MD; Michaël Chassé, MD, PhD; Prosanto Chaudhury, MD; Sonny Dhanani, MD; Shane W. English, MD; Anne Julie Frenette, PhD; Steven Hanna, PhD; Gregory Knoll, MD; François Lauzier, MD; Simon Oczkowski, MD; Bram Rochwerg, MD; Khaled Shamseddin, MD; Marat Slessarev, MD, PhD; Darin Treleaven, MD; Alexis F. Turgeon, MD; Matthew J. Weiss, MD; Markus Selzner, MD; Maureen O. Meade, MD

doi:10.1097/TXD.0000000000001519

Transplantation Direct (Sep 2023)

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies

Frédérick D’Aragon, MD,
William Rousseau, MD,
Ruth Breau, BA,
Daniel Aminaei, BSc,
Carole Ichai, MD,
Gordon J. Boyd, MD, PhD,
Karen E. A. Burns, MD,
Héloïse Cardinal, MD, PhD,
François-Martin Carrier, MD,
Michaël Chassé, MD, PhD,
Prosanto Chaudhury, MD,
Sonny Dhanani, MD,
Shane W. English, MD,
Anne Julie Frenette, PhD,
Steven Hanna, PhD,
Gregory Knoll, MD,
François Lauzier, MD,
Simon Oczkowski, MD,
Bram Rochwerg, MD,
Khaled Shamseddin, MD,
Marat Slessarev, MD, PhD,
Darin Treleaven, MD,
Alexis F. Turgeon, MD,
Matthew J. Weiss, MD,
Markus Selzner, MD,
Maureen O. Meade, MD

Affiliations

Frédérick D’Aragon, MD: 1 Department of Anesthesiology, Université de Sherbrooke, Sherbrooke, QC, Canada.
William Rousseau, MD: 3 Faculty of Medicine and Health Sciences, Université de Sherbrooke, QC, Canada.
Ruth Breau, BA: 4 Department of Health Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Daniel Aminaei, BSc: 4 Department of Health Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Carole Ichai, MD: 5 Intensive Care Unit, University Hospital of Nice, Nice, France.
Gordon J. Boyd, MD, PhD: 6 Division of Neurology, Department of Medicine, Queen’s University, Kingston, ON, Canada.
Karen E. A. Burns, MD: 4 Department of Health Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Héloïse Cardinal, MD, PhD: 10 Department of Nephrology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
François-Martin Carrier, MD: 11 Department of Anesthesiology, Université de Montréal, Montreal, QC, Canada.
Michaël Chassé, MD, PhD: 12 Department of Critical Care, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
Prosanto Chaudhury, MD: 13 Department of Surgery and Oncology, McGill University, Montreal, QC, Canada.
Sonny Dhanani, MD: 14 Division of Critical Care, Department of Pediatrics, Children’s Hospital of Eastern Ontario and University of Ottawa, Ottawa, ON, Canada.
Shane W. English, MD: 15 Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Anne Julie Frenette, PhD: 17 Faculty of Pharmacy, Université de Montreal, Montreal, QC, Canada.
Steven Hanna, PhD: 3 Faculty of Medicine and Health Sciences, Université de Sherbrooke, QC, Canada.
Gregory Knoll, MD: 15 Ottawa Hospital Research Institute, Ottawa, ON, Canada.
François Lauzier, MD: 19 Department of Medicine, Université Laval, Quebec City, QC, Canada.
Simon Oczkowski, MD: 4 Department of Health Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Bram Rochwerg, MD: 4 Department of Health Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Khaled Shamseddin, MD: 22 Division of Nephrology, Department of Medicine, Queen’s University, Kingston, ON, Canada.
Marat Slessarev, MD, PhD: 23 Division of Critical Care, Department of Medicine, Western University, London, ON, Canada.
Darin Treleaven, MD: 24 Department of Medicine, McMaster University, Hamilton, ON, Canada.
Alexis F. Turgeon, MD: 20 Population Health and Optimal Health Practice Research Unit, CHU de Québec-Université Laval Research Center, Quebec City, QC, Canada.
Matthew J. Weiss, MD: 20 Population Health and Optimal Health Practice Research Unit, CHU de Québec-Université Laval Research Center, Quebec City, QC, Canada.
Markus Selzner, MD: 27 Department of General Surgery, University of Toronto and Toronto General Hospital, University Health Network, Toronto, ON, Canada.
Maureen O. Meade, MD: 4 Department of Health Evidence and Impact, McMaster University, Hamilton, ON, Canada.

DOI: https://doi.org/10.1097/TXD.0000000000001519
Journal volume & issue: Vol. 9, no. 9
p. e1519

Abstract

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Background. Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia–reperfusion injury to improve transplant outcomes. Methods. We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results. Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions. Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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