Impact of human leukocyte antigen matching and recipients' panel reactive antibodies on two-year outcome in presensitized renal allograft recipients.
BACKGROUND
Renal transplantation in sensitized candidates remains a highly significant challenge worldwide. The production of panel reactive antibody (PRA) against human leukocyte antigen (HLA) is a major risk factor in presensitized recipients. The aim of this study was to evaluate the impact of HLA matching and recipients' PRA on two-year outcome in presensitized renal allograft recipients.


METHODS
We determined the percentage of panel reactivity and specificity of anti-HLA immunoglobulin (Ig) G antibodies in 73 presensitized renal allograft recipients compared with 81 unsensitized recipients (control group). HLA genotyping of both recipients and corresponding donors was performed by PCR with sequence-specific primers (PCR-SSP). We analyzed the factors influencing the early graft outcome (two-year rejection rates and survival rates of the grafts), including HLA mismatching, class and degree of panel reactivity, and target antigen of donors.


RESULTS
Presensitized recipients had a worse two-year outcome than unsensitized recipients (P = 0.019 for rejection rate, P = 0.01 for survival rate). The difference in number of HLA-mismatched alleles with either 6-antigen matching (Ag M) standard or amino acid residue matching (Res M) standard was not significant between the rejection and non-rejection groups of presensitized recipients or between the graft survival group and graft loss group. Compared with the control group, recipients with both PRA-I and PRA-II antibodies had a significantly worse two-year outcome (P = 0.001 for rejection rate, P = 0.002 for survival rate). The two-year outcomes of the peak PRA >/= 50% group and its subgroup, at-transplant PRA > or = 50% group, were significantly worse compared with the control group (P = 0.025 and P = 0.001 for rejection rate, P = 0.043 and P = 0.024 for survival rate). The rejection rates of the at-transplant target antigen positive group and its subgroup, HLA-I target antigen positive group, were significantly higher than the control group (P = 0.001 and P = 0.001), target antigen negative group (P = 0.003 and P = 0.001), and peak target antigen positive with negative at-transplant target antigen group (P = 0.024 and P = 0.002). Two-year graft survival rates of the target antigen positive group and HLA-I target antigen positive group were significantly lower than the control group (P = 0.012 and P = 0.001). The two-year outcome of target antigen unknown group was similar to that of the target antigen positive group. Presensitized recipients with pre-transplant plasmapheresis or immunoadsorption (PRA prepared group) had a better but non-significant two-year outcome than the control group. However, the PRA unprepared presensitized recipients were different to the control group (P = 0.004 for rejection rate and P = 0.005 for survival rate). Hyperacute rejection (HR) occurred in three recipients with positive HLA-I target antigen and without mismatch according to Res M and in one case with positive PRA-II (for an unknown target antigen). No HR occurred in eight cases with positive HLA-II target antigens.


CONCLUSIONS
Pre-transplant PRA preparations might improve the access of presensitized patients to renal donors. Avoiding antigen-positive donors remains a fundamental measure in preventing HR and early rejections.
Meng
Hui-lin
HL
Minimally Invasive Urology Center Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
Jin
Xun-bo
XB
Li
Xiang-tie
XT
Wang
Hong-wei
HW
Lü
Jia-ju
JJ
D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000276:immunology*; D016896:Treatment Outcome
D006680:HLA Antigens; D007518:Isoantibodies