title: Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation.
abstract: BACKGROUND
  The use of expanded criteria donor kidneys (ECD) had been associated with worse outcomes. Whole gene expression of pre-implantation allograft biopsies from deceased donor kidneys (DDKs) was evaluated to compare the effect of pulsatile pump preservation (PPP) vs. cold storage preservation (CSP) on standard and ECD kidneys.
  
  
  RESULTS
  99 pre-implantation DDK biopsies were studied using gene expression with GeneChips. Kidneys transplant recipients were followed post transplantation for 35.8 months (range = 24-62). The PPP group included 60 biopsies (cold ischemia time (CIT) = 1,367+/-509 minutes) and the CSP group included 39 biopsies (CIT = 1,022+/-485 minutes) (P<0.001). Donor age (42.0±14.6 vs. 34.1±14.2 years, P = 0.009) and the percentage of ECD kidneys (PPP = 35% vs. CSP = 12.8%, P = 0.012) were significantly different between groups. A two-sample t-test was performed, and probe sets having a P<0.001 were considered significant. Probe set level linear models were fit using cold ischemia time and CSP/PPP as independent variables to determine significant probe sets (P<0.001) between groups after adjusting for cold ischemia time. Thus, 43 significant genes were identified (P<0.001). Over-expression of genes associated with inflammation (CD86, CD209, CLEC4, EGFR2, TFF3, among others) was observed in the CSP group. Cell-to-cell signaling and interaction, and antigen presentation were the most important pathways with genes significantly over-expressed in CSP kidneys. When the analysis was restricted to ECD kidneys, genes involved in inflammation were also differentially up-regulated in ECD kidneys undergoing CSP. However, graft survival at the end of the study was similar between groups (P = 0.2). Moreover, the incidence of delayed graft function was not significant between groups.
  
  
  CONCLUSIONS
  Inflammation was the most important up-regulated pattern associated with pre-implantation biopsies undergoing CSP even when the PPP group has a larger number of ECD kidneys. No significant difference was observed in delayed graft function incidence and graft function post-transplantation. These findings support the use of PPP in ECD donor kidneys.
authors.affiliation: Translational Genomics Transplant Laboratory, University of Virginia, Charlottesville, Virginia, United States of America. vrm3n@Virginia.edu
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Mas
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Archer
authors.forename: Catherine I
authors.initials: CI
authors.lastname: Dumur
authors.forename: Mariano J
authors.initials: MJ
authors.lastname: Scian
authors.forename: Jihee L
authors.initials: JL
authors.lastname: Suh
authors.forename: Anne L
authors.initials: AL
authors.lastname: King
authors.forename: Megan E
authors.initials: ME
authors.lastname: Wardius
authors.forename: Julie A
authors.initials: JA
authors.lastname: Straub
authors.forename: Marc P
authors.initials: MP
authors.lastname: Posner
authors.forename: Kenneth
authors.initials: K
authors.lastname: Brayman
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Maluf
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002102:Cadaver; D051799:Delayed Graft Function / Q000453:epidemiology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D016030:Kidney Transplantation / Q000276:immunology / Q000379:methods; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods*; D055815:Young Adult