Successful Transplantation of Donor Specific Antibody Positive, Crossmatch Negative (Ahg/Fcxm)renal Allograft Recipients

Abstract

Successful combined liver kidney transplantation (CLKT) despite pre-transplant positive cross match (+ CXM) has been reported implying immunoprotective effect of liver allograft (LA) on renal allograft (RA). However, severe acute humoral rejection with RA loss has been documented suggesting LA may not always protect RA. Aim: To examine the effects of pre-transplant + CXM on RA outcome in CLKT. Method: A total of 1401 CLKT recipients for whom CXM data available were identifi ed from UNOS data base from 1986-2006. Of these, 242 (17.3%) had +CXM and data was analyzed for acute rejection rate and RA outcome. The signifi cant results are summarized below. Variable Negative CXM N = 1159 Positive CXM N = 242 p-value Recipient: Female 374(32%) 136 (56%) 0.001 % Class I PRA 25.9±26.5 66.3±40.5 0.001 % Class II PRA 31.0±29.3 56.4±36.3 0.013 treated for rejection 69/606 (11%) 24/150 (16%) 0.026 Length of stay: Admission to discharge Days 28.8±33.2(N=838) Days 37.3±46.0(N=155) 0.028 Results:The demographic and clinical data were similar between +CXM and Negative CXM groups. The rejection rate was signifi cantly higher and the length of stay was signifi cantly longer in +CXM group as shown in the table. The RA survival rates were 8%, 7% and 6% lower at 1, 3 and 5 years post transplant respectively among + CXM recipients. However, this did not reach signifi cance mostly due to small sample size (p=0.11). The inferior RA outcome is seen during the initial few years after transplantation that disappears after 9 years. Conclusion:In CLKT, pre-transplant +CXM can result in higher RA rejection rate and longer length of stay in hospital. LA may not always confer immunological protection to RA in + CXM CLKT and its true burden may be under recognized since CXM is not routinely performed in all CLKT. Study of antibody specifi cities or LA volume to determine the effect of +CXM on RA outcome is essential. Historically, the pretransplant (Tx) crossmatch (XM) alone was used to pair immunologically appropriate donors and recipients (recips) for transplantation. Recips were then transplanted following a negative (neg) donor-recipient antihuman globulin (AHG) XM and, more recently, following a neg, more sensitive, fl ow cytometry XM (FCXM). In addition, the presence of HLA antibodies (Abs) and their specifi cities can be identifi ed in patient sera by Luminex and single antigen bead technology. Would there be an increased immune and clinical risk if the preTx evaluation yielded neg donor specifi c AHG and FCXMs albeit in the presence of a positively identifi ed donor-specifi c HLA Ab (DSA) in patient sera? To address this question we prospectively transplanted 17 renal allograft recips (14 with deceased and 3 with living related donors, including 5 ReTx and 12 primary recips, 8 females and 9 males; 6 of African American, 8 of Caucasian, 2 of Hispanic and 1 of Asian heritage). Immunosuppression consisted of Thymoglobulin induction followed by Sirolimus (N=13), Cyclosporine, Mycophenolate Mofetil (N=4) and Prednisone maintenance therapy. No p...