Projectdetails

of


Volatile Anesthetic Protection of Renal transplants - 2 (VAPOR-2).

Keywords:
kidney transplantation anesthesiology biochemie

Researchers:
R. Spanjersberg
G. Nieuwenhuijs

Nature of the research:
VAPOR-2 trial is whether a volatile based anesthesia is able to reduce IRI in deceased donor kidney transplantation clinically manifesting in a reduction of DGF compared to a propofol based anesthesia

Fields of study:
anesthesiology surgery nephrology

Background / introduction
For patients with end stage renal disease (ESRD), transplantation is still the optimal treatment. Long term survival with kidney transplantation is dramatically better than dialysis and transplantation provides a sustainably higher quality of life. Unfortunately there is a persistent shortage of donor organs, therefor many transplant centres have established large living donor programmes and transplant teams are also now accepting more older and higher risk organs retrieved from deceased donors. The use of these extended criteria donors (ECD) has affected outcomes after transplantation due to an often suboptimal quality of the donor organ.1,2 As we will face more complex donors in the future with a reduced viability such as unstable donation after brain death (DBD) donors, donation after circulatory death (DCD) donors, and ECD, the challenge in transplantation is to be able to use these donor sources, however, without compromising successful immediate function and long-term graft survival after transplantation. It is therefore imperative that the condition of every graft-to-be ought to be optimised prior to or at time of transplantation, achieving the best possible post-transplant function and avoiding primary non function (PNF), delayed graft function (DGF), and rejection with chronic graft failure.

During the procedure of organ donation and transplantation a number of potentially harmful processes will inevitably occur, affecting the viability of the kidney graft. Both donor and recipient are subjected to anesthesia and surgery, which will produce a sequence of systemic and local changes including a significant pro-inflammatory and pro-coagulatory response.3 The donor organ is by definition exposed to a number of phases of injury from the moment that the donor suffers from cerebral injury until the kidney is reconnected to the circulation in the recipient. These phases include a profound systemic and local pro-inflammatory and pro-coagulatory response during donor management and retrieval, associated with hypoxia and ischemia of the kidney. In addition, prolonged warm ischemia in the DCD donor will affect the viability of the donor kidney. These combined effects on the graft-to-be result in a cascade of renal damage that will reveal itself at the time of transplantation when the donor kidney is reperfused in the recipient and has been named ischemia-reperfusion injury (IRI).4

Volatile anaesthetics (VA) like sevoflurane and isoflurane interfere with many of the processes underlying the pathophysiology of IRI and potentially could have a protective effect in the setting of (kidney) transplantation. Therefor we have designed the Volatile Anesthetic Protection Of Renal transplants (VAPOR)-project. In VAPOR-1, a single center RCT in living donor kidney transplantation and first step of this project, a significantly lower acute rejection rate was noticed in the sevoflurane group compared to the propofol group (intravenous anaesthetic).5 When reproducible, these findings may have important implications for transplantation. The use of volatile anaesthetics is not associated with extra costs and can be implemented very easily since volatile anaesthetic regimens are widely used and generally accepted.

We therefore proceeded with the VAPOR-2 trial, an international multicenter RCT looking at the effect of these 2 anesthetic agents in 488 recipients of deceased donor kidneys.
The VAPOR-2 started in May 2017 and currently runs in Denmark, Spain and the Netherlands. Norway will follow soon. Until now, 149 patients have been included.
Research question / problem definition
The main research question of the VAPOR-2 trial is whether a volatile based anesthesia is able to reduce IRI in deceased donor kidney transplantation clinically manifesting in a reduction of DGF compared to a propofol based anesthesia. DGF is defined as the need for dialyses within the first week after transplantation. VAPOR-2 will provide us with a large (biomaterial) database and additional research questions can be addressed upon your interest such as role of various biomarkers in kidney transplantation.

Additionally we would like to run a third and last study in the VAPOR project (VAPOR-3) in which we will study the influence of anesthetics on the immune systemby means of immunophenotyping
Workplan
- participation in an international study, maintaining contact with all (international) study sites (i.e. writing of newsletters, site visits etc).
- data collection, data entry and coordination of follow-up visits for patients in Groningen
- possibility to develop related research questions in your own field of interest
- creating yearly safety reports for the medical ethical committee
- developing of writing skills and possibility to publish in international scientific journals
- development of presentation skills by visiting international congresses
- support of the research agency of the department of Anesthesiology
References
1. Cooper JT, Chin LT, Krieger NR, Fernandez LA, Foley DP, Becker YT et al. Donation after cardiac death: the university of wisconsin experience with renal transplantation. Am J Transplant 2004; 4:1490-94
2. Koffman G, Gambaro G. Renal transplantation from non-heart-beating donors: a review of the European experience. J Nephrol. 2003; 16:334-41
3. Nijboer WN, Schuurs TA, van der Hoeven JA, Leuvenink HG, van der Heide JJ, van Goor H, Ploeg RJ. Effects of brain death on stress and inflammatory response in the human donor kidney. Transplant Proc. 2005; 37(1):367-9
4. Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet. 2004; 364(9447):1814-27
5. Nieuwenhuijs-Moeke GJ, Nieuwenhuijs VB, Seelen MAJ, Berger SP, Heuvel MC van den, Burgerhof JGM et al. Propofol-based anesthesia versus sevoflurane based anesthesia for living donor kidney transplantation: results of the VAPOR-1 randomized controlled trial, Br J Anaesth. 2017;118(5):720-32
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