title: Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation.
abstract: 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.
authors.affiliation: William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: taner.timucin@mayo.edu.
authors.forename: Timucin
authors.initials: T
authors.lastname: Taner
authors.affiliation: William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Walter D
authors.initials: WD
authors.lastname: Park
authors.affiliation: William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stegall
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D012189:Retrospective Studies; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D006680:HLA Antigens
keywords: alloimmunity; gene expression; kidney transplantation; liver transplantation; rejection; simultaneous liver-kidney transplantation