The Impact of Cytokine Release Caused By Induction Immunosupression On Nitric Oxide in Renal transplantation
1University of Cardiff, Cardiff, United Kingdom
2University Hospital of Wales, Cardiff, United Kingdom.
Meeting: 2015 American Transplant Congress
Abstract number: D105
Keywords: Donors, Kidney transplantation, non-heart-beating, Warm ischemia
Session Information
Session Name: Poster Session D: Innate Immunity in Transplantation
Session Type: Poster Session
Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Introduction
Varying induction immunosuppression regimens have a differential impact on the pattern of cytokine release. Pro-inflammatory cytokines stimulate endothelial cells causing secretion of NO. Serum nitrite (NO2) sensitively reflects endothelial nitric oxide (NO) formation corresponding to acute changes in regional eNOS activity. The Aim of the current study was to see if among DCD kidneys the change of NO2 depends on factors associated with reperfusion injury and if differential induction influences this change by effecting cytokine release.
Methods
In 35 DCD transplants we measured the plasma levels of NO2 by ozone chemiluminescence prior to anaesthesia and at 7 other time points pre and post perfusion and analysed their change. We also measured the level of various cytokines using a Luminex multi-cytokine kit and correlated them with the induction regime used.
Results
ATG increases the release of TNF-α, IFN-γ, IL-6, IL-10 and IL-17. IL-2, TNF-α and IL-10 are increased more by ATG compared to Campath (p=0.003, 0.07, and 0.03 respectively) at 2h post perfusion. In addition the respective areas under the curve of cytokine values over time are larger in the ATG patients for all of the above three cytokines. At regression analysis the change of NO2 at 8 h post perfusion was related to the primary WIT (p=0.001), the age of the recipient (p=0.004) and to induction with Campath (p=0.04).
In order to see if the change in NO2 was attributable solely to the pro-inflammatory cytokine release caused by ATG or Campath, we checked separately the changes of NO2 in patients who received Simulect. In patients in the Simulect group the change of NO2 at 8h post perfusion was still dependent on the primary warm ischemia (p=0.008) and the recipient age (p=0.01).
Conclusion
The levels of NO2 post perfusion in DCD transplants are affected by warm ischemia in the donor and the age of the donor and the recipient. In spite of the up-regulation of various cytokines by ATG and/or Campath this change of NO2 seems not to be dependent entirely on induction since it also occurs on patients receiving Simulect. This study suggests that NO2 levels post perfusion are linked to factors affecting reperfusion injury and differential induction regimes might be modifying those factors via their varying effect on cytokine release.
To cite this abstract in AMA style:
Johns R, Laftsidis M, Burrows E, Edwards F, Ablorsu E, James P, Phillips A, Asderakis A. The Impact of Cytokine Release Caused By Induction Immunosupression On Nitric Oxide in Renal transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/the-impact-of-cytokine-release-caused-by-induction-immunosupression-on-nitric-oxide-in-renal-transplantation/. Accessed May 17, 2025.« Back to 2015 American Transplant Congress