Re-exposure to mismatched HLA class I is a significant risk factor for graft loss: multivariable analysis of 259 kidney retransplants.
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.
House
Andrew A
AA
Multi-Organ Transplant Program, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada. andrew.house@lhsc.on.ca
Chang
Peter C W
PC
Luke
Patrick P
PP
Leckie
Stephen H
SH
Howson
William T
WT
Ball
Edward J
EJ
Tan
Ann K L
AK
Rehman
Faisal
F
Muirhead
Norman
N
Hollomby
David J
DJ
McAlister
Vivian C
VC
Hodsman
Anthony B
AB
Jevnikar
Anthony M
AM
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
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I