M. Said

Rabbit Anti-Thymocyte Globulin (rATG) Induction Therapy Followed by Tacrolimus Conversion to Sirolimus at 3 Months Does Not Expand TREG Cells: 514

A variety of therapeutic strategies have been employed to prolong renal transplant survival including creating a more toleragenic immune state and minimizing potential drug toxicity. Since rATG and sirolimus (SLR) may fulfill both requirements, we examined the constituents of peripheral blood leukocytes (PBL) in a prospective trial of rATG induction followed by CNI conversion at 3 mos. from tacrolimus (TAC) to SRL. All 63 renal transplant recipients (RTR) received rATG induction (3-5 mg/kg/total dose), TAC (10-15 ng/ml), EC-MPS (Myfortic) and prednisone for 3 mos. RTR with normal 3 mo. protocol biopsies were then randomized to receive either low-dose TAC (4-6 ng/ml) or SRL (6-10 ng/ml) followed by a protocol biopsy at 12 mos. PBL subsets were enumerated by flow cytometry at 3 and 12 mos. At 3 mo., rATG led to significant depletion in all PBL subsets except CD8 cells. Seven patients had subclinical rejection (SCR) (1 Grade 1A, 6 borderline) on protocol biopsy. Compared to the 56 RTR without SCR, the PBL profile of these 7 RTR showed a higher number of CD4 naïve cells. At 12 mo., both the TAC and SRL groups showed persistent B, NK, NKT and CD4 cell depletion and an increased CD4 memory/naive ratio. Irrespective of TAC or SRL therapy, Treg absolute cell numbers did not recover and the Treg/total or memory CD4 ratios remained normal. Thus, the combination of rATG/TAC/ECMPA/steroids provided adequate short-term immunosuppression with no clinically apparent ACR and approximately 10% SCR. The relatively higher number of CD4 naïve cells in RTR with SCR suggests the need for increased doses of rATG for adequate initial immunosuppression. The lack of Tregs expansion may be due to the initial use of TAC or to an insufficient rATG dose. Thus, the early CNI conversion strategy does not promote a more toleragenic PBL profile.

LOW DOSE RABBIT ANTI-THYMOCYTE GLOBULIN INDUCTION IN LOW RISK RENAL TRANSPLANT RECIPIENTS: 8 YEARS FOLLOW UP.: 85

Introduction: Antibody induction therapies are effective in reducing the rates of acute rejection (AR) but their effects on long-term renal allograft function and survival remain controversial. Because of the questionable long-term benefit gained by using antibody induction and their inherent risks, full dose lymphocyte depleting induction therapy for low risk patients is usually avoided. However, the benefit and risks associated with low-dose (3-5mg/kg total dose) rabbit antithymocyte globulin (rATG) induction in a low-risk population has not been explored. Over the past 8 years, our center has routinely used low-dose rATG as well as anti-IL2 receptor antibody, Basiliximab (BSX), induction therapy for all low-risk renal transplant recipients. We now report on the long-term outcomes in this patient population. Methods: The medical records of all renal transplant recipients from 6/01 to 6/09 were reviewed. Only patients who received lowdose rATG or BSX induction were included. Grafts lost to surgical complications or biopsy proven recurrent of disease were excluded. Low risk patients were considered to be white, have a PRA < 30% and non-DCD kidney donor recipients. We compared the risk of acute rejection and graft survival in low risk patients for both living donor and deceased donor recipients. The average dose of rATG was 3.1± 1.2 mg/kg and all patients received two doses of 20 mg BSX. Results: Of the low-risk deceased donor recipients, 40 received BSX (group 1) and 145 low-dose rATG (group 2). Living donor recipients were treated with BSX in 20 cases (group 3) and rATG in 64 cases (group 4). The groups did not differ in their demographic or donor characteristics. Maintenance immunosuppressive therapy was equally represented in all groups. Overall, pt. sur. was not different between Lo-rATG or BSX groups received LD or DD (96.9 vs. 95%, p=0. and 82.8 vs.72.5%, p=0.1, respectively). Low-dose rATG was associated with better long-term, gft. Sur. compared to BSX (Fig.1). For DD recipients, 8 yr. gft. Sur. were better with LorATG than with BSX (76.6 vs. 55%, p=0.007). All living donor recipients had excellent long-term survival and function that did not differ between groups (rATG 95.3 vs. BSX 95%). For LD recipients rATG induction was associated with a significantly lower rate of acute rejection (rATG 7.8 vs. BSX 35%, p=0.002). One, five and 8years mean serum creatinine levels; viral infection and cancer rates were not statistically significantly different amongst these groups. Conclusion: Our data demonstrate, for the first time, that low-dose rATG induction therapy has added beneficial long-term effects in low-risk patients compared to anti-IL2R therapy without incurring additional risks of infectious or malignant diseases.