Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies-Reference-Cited by-同舟云学术

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

Published:2023-08-28 Issue:9 Volume:9 Page:e1519
ISSN:2373-8731
Container-title:Transplantation Direct
language:en
Short-container-title:

Author:

D’Aragon Frédérick¹²,Rousseau William³,Breau Ruth⁴,Aminaei Daniel⁴,Ichai Carole⁵,Boyd Gordon J.⁶⁷,Burns Karen E. A.⁴⁸⁹,Cardinal Héloïse¹⁰,Carrier François-Martin¹¹¹²,Chassé Michaël¹²,Chaudhury Prosanto¹³,Dhanani Sonny¹⁴¹⁵,English Shane W.¹⁵¹⁶,Frenette Anne Julie¹⁷,Hanna Steven³,Knoll Gregory¹⁵¹⁸,Lauzier François¹⁹²⁰,Oczkowski Simon⁴²¹,Rochwerg Bram⁴²¹,Shamseddin Khaled²²,Slessarev Marat²³,Treleaven Darin²⁴,Turgeon Alexis F.²⁰²⁵,Weiss Matthew J.²⁰²⁶,Selzner Markus²⁷²⁸,Meade Maureen O.⁴²¹

Affiliation:

1. Department of Anesthesiology, Université de Sherbrooke, Sherbrooke, QC, Canada.

2. Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, QC, Canada.

3. Faculty of Medicine and Health Sciences, Université de Sherbrooke, QC, Canada.

4. Department of Health Evidence and Impact, McMaster University, Hamilton, ON, Canada.

5. Intensive Care Unit, University Hospital of Nice, Nice, France.

6. Division of Neurology, Department of Medicine, Queen’s University, Kingston, ON, Canada.

7. Department of Critical Care Medicine, Queen’s University, Kingston, ON, Canada.

8. Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.

9. Li Ka Shing Knowledge Institute, University Health Toronto—St. Michael’s Hospital, Toronto, ON, Canada.

10. Department of Nephrology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.

11. Department of Anesthesiology, Université de Montréal, Montreal, QC, Canada.

12. Department of Critical Care, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.

13. Department of Surgery and Oncology, McGill University, Montreal, QC, Canada.

14. Division of Critical Care, Department of Pediatrics, Children’s Hospital of Eastern Ontario and University of Ottawa, Ottawa, ON, Canada.

15. Ottawa Hospital Research Institute, Ottawa, ON, Canada.

16. Department of Medicine, University of Ottawa, Ottawa, ON, Canada.

17. Faculty of Pharmacy, Université de Montreal, Montreal, QC, Canada.

18. Division of Nephrology, Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON, Canada.

19. Department of Medicine, Université Laval, Quebec City, QC, Canada.

20. Population Health and Optimal Health Practice Research Unit, CHU de Québec-Université Laval Research Center, Quebec City, QC, Canada.

21. Division of Critical Care, Department of Medicine, McMaster University, Hamilton, ON, Canada.

22. Division of Nephrology, Department of Medicine, Queen’s University, Kingston, ON, Canada.

23. Division of Critical Care, Department of Medicine, Western University, London, ON, Canada.

24. Department of Medicine, McMaster University, Hamilton, ON, Canada.

25. Departments of Anesthesiology and Critical Care Medicine, Université Laval, Quebec City, QC, Canada.

26. Transplant Québec, QC, Canada.

27. Department of General Surgery, University of Toronto and Toronto General Hospital, University Health Network, Toronto, ON, Canada.

28. Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada.

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Transplantation

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