title: Re-exposure to mismatched HLA class I is a significant risk factor for graft loss: multivariable analysis of 259 kidney retransplants.
abstract: BACKGROUND
  Kidney retransplants carry increased immunologic risk. One possible contributor to this risk may be re-exposure to human leukocyte antigens (HLA) common to a previous donor but foreign to the recipient. Conflicting publications have assessed this risk, so to examine our experience 259 kidney retransplants were analyzed.
  
  
  METHODS
  A retrospective cohort of retransplant patients from 1973 to 2005 with minimum 12 months follow up was examined. Using multivariable modeling, important confounders were controlled for identifying factors significantly affecting graft survival.
  
  
  RESULTS
  Re-exposure to HLA class I (HLA-A or B) antigens, peak panel reactive antibodies and donor source were the most important determinants of allograft survival, despite a negative conventional or anti-human globulin-augmented T cell crossmatch. We failed to demonstrate that recipient re-exposure to HLA class II (HLA-DR) or positive B cell crossmatch were associated with adverse outcomes. Sample size and molecular versus serologic methods may have influenced the former, while inability to determine antibody specificities may have influenced the latter. Controlling for other variables, the adjusted risk of graft loss associated with re-exposure to HLA class I increased by 71% (P=0.006) and occurred early, consistent with recall of memory cytotoxic T lymphocyte or antibody responses.
  
  
  CONCLUSIONS
  Kidney recipients re-exposed to mismatched HLA class I antigens appear to be at heightened risk of early graft loss. Such patients may benefit from pretransplant identification of donor specific antibodies using solid phase methods and heightened vigilance for acute rejection. Future studies may indicate whether more intensive immunosuppression for these patients is warranted.
authors: Multi-Organ Transplant Program, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada. andrew.house@lhsc.on.ca
authors: Andrew A
authors: AA
authors: House
authors: Peter C W
authors: PC
authors: Chang
authors: Patrick P
authors: PP
authors: Luke
authors: Stephen H
authors: SH
authors: Leckie
authors: William T
authors: WT
authors: Howson
authors: Edward J
authors: EJ
authors: Ball
authors: Ann K L
authors: AK
authors: Tan
authors: Faisal
authors: F
authors: Rehman
authors: Norman
authors: N
authors: Muirhead
authors: David J
authors: DJ
authors: Hollomby
authors: Vivian C
authors: VC
authors: McAlister
authors: Anthony B
authors: AB
authors: Hodsman
authors: Anthony M
authors: AM
authors: Jevnikar
mesh_terms: D005260:Female; D006084:Graft Rejection / Q000453:epidemiology*; D006085:Graft Survival / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology; D006648:Histocompatibility; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D012086:Reoperation; D012306:Risk
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I