7 �� 3.0 (�� SD) months after transplantation (Table 4). In ATG-F and control groups, the ad hoc analysis showed an incidence of rejection of 83.3% and 31% during the whole study period (p = 0.008), 50% and 23% from transplantation to month 3 (p = ns), and 83.3% and 7.7% from month 4 to month 12, respectively (p < 0.001). Rejection episodes occurring before 3 months were treated with steroid boluses in 31.6% and 18.8% of recipients in the ATG-F and control groups, respectively (p = ns). Rejection episodes developing during weaning (beyond 3 months) were mild and did not require treatment with steroid boluses. Antibody treatment was not required to reverse any rejection episode. Both the CX-5461 in vivo
intention-to-treat and ad hoc analyses revealed that recipients from the ATG-F group received significantly lower doses of tacrolimus and exhibited lower tacrolimus trough serum levels than recipients from the control group (Figure 2). The accumulated dose of steroids administered as maintenance therapy was also significantly Saracatinib
higher in the control than in the ATG-F group both in the intention-to-treat (1031 �� 1166 mg vs. 3236 �� 884 mg, respectively; p < 0.001) and ad hoc (680 �� 1048 mg vs. 3181 �� 945 mg, respectively; p < 0.001) analyses. Adverse events are shown in Table 5. The rate of anastomotic biliary strictures was significantly increased in the control group. A nonstatistically significant trend toward increased rate of infections and de novo diabetes in the control group was also observed. Renal function as assessed by both serum creatinine and MDRD-calculated glomerular filtration rate was similar in both groups during the entire duration of the study (similar results were obtained in the ad hoc analysis; data not shown). Lymphocyte counts were lower in ATG-F recipients than in control patients at day 2 and month 3 after transplantation (Figure 3). Before transplantation both groups of patients exhibited similar frequencies and absolute numbers of total CD3+, CD4+ and CD8+ T cells (Figure 4A�CC, respectively) while ATG-F recipients exhibited a higher frequency (but not absolute numbers) of central memory CD8+CD62LhighCD45RA- T cells (14.93 �� 7.32% vs. 6.66 �� 6.41%, p = 0.012). Six Forskolin manufacturer
months after transplantation ATG-F recipients displayed decreased relative and absolute numbers of total CD4+ T cells and CD4+CD62LhighCD45RA+ T cells (Figure 4B and E) and increased relative and absolute numbers of CD8+CD62LlowCD45RA- effector memory T cells (Figure 4H). One year after transplantation only the absolute numbers of total CD4+ T cells were still significantly decreased in ATG-F recipients as compared with the control group (data not shown). Pretransplantation the frequency of CD4+Foxp3+ T cells was similar in the two treatment groups. The numbers of regulatory T cells pretransplantation did not correlate with the development of early acute rejection episodes.