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Background Calcineurin inhibitor (CNI) based immunosuppression in liver transplantation (LTx) is associated with acute and chronic deterioration of kidney function. Delaying CNI initiation by using induction rabbit anti-thymocyte globulin (rATG) may provide kidneys with adequate time to recover from a perioperative insult reducing the risk of early post-LTx renal deterioration. Methods This was an open-label, multicenter, randomized controlled clinical trial comparing use of induction rATG with delayed CNI initiation (day-10) against upfront CNI commencement (SOC; standard of care) in those patients deemed at standard risk of postoperative renal dysfunction following LTx. The primary end point was change in (delta) creatinine from baseline to month-12. Results Fifty-five patients were enrolled in each study arm. Mean Tacrolimus levels remained comparable in both groups from day-10 throughout the study period. A significant difference in delta creatinine was observed between rATG and SOC groups at 9-months (p=0.03) but not at month-12 (p=0.05). eGFR levels remained comparable between cohorts at all time points. Rates of biopsy-proven acute rejection at 1-year were similar between groups (16.3 vs 12.7%, p= 0.58). rATG showed no significant adverse effects. Survival at 12-months was comparable between groups (p= 0.48). Conclusions Although the use of induction rATG and concurrent CNI deferral in this study did not demonstrate a significant difference in delta creatinine at 1 year, these results indicate a potential role for rATG in preserving early kidney function, especially when considered with CNI deferral beyond 10 days and/or lower target Tacrolimus levels, with acceptable safety and treatment efficacy.

Key Points 1. Our increasing understanding of signaling pathways and cellular interactions in transplant immunobiology and the availability of novel immunosuppressive agents have facilitated targeted strategies. 2. The driving forces behind the development of new immunosuppressive regimens are the long-term complications of current immunosuppressive regimens (particularly renal dysfunction and metabolic disturbances). 3. By regulatory mandate, the requirement for the primary endpoint to be a composite of death, graft loss, and rejection remains intact; however, current and future clinical trials could incorporate key secondary endpoints that address renal and metabolic derangements. Liver Transpl, 2011. © 2011 AASLD.