TY - JOUR
T1 - Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation
AU - Taner, Timucin
AU - Park, Walter D.
AU - Stegall, Mark D.
N1 - Publisher Copyright:
© 2017 International Society of Nephrology
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match–positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match–positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match–negative kidney transplants. These changes were not found in cross-match–positive simultaneous liver-kidney transplant biopsies when compared to cross-match–negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match–positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match–negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match–positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms.
AB - Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match–positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match–positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match–negative kidney transplants. These changes were not found in cross-match–positive simultaneous liver-kidney transplant biopsies when compared to cross-match–negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match–positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match–negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match–positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms.
KW - alloimmunity
KW - gene expression
KW - kidney transplantation
KW - liver transplantation
KW - rejection
KW - simultaneous liver-kidney transplantation
UR - http://www.scopus.com/inward/record.url?scp=85013399300&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85013399300&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2016.12.016
DO - 10.1016/j.kint.2016.12.016
M3 - Article
C2 - 28233612
AN - SCOPUS:85013399300
SN - 0085-2538
VL - 91
SP - 1193
EP - 1202
JO - Kidney international
JF - Kidney international
IS - 5
ER -