A Randomized Controlled Clinical Trial of Thymoglobulin® After Liver Transplantation

Functional recovery of renal function from acute renal failure occurs in 75% of patients at
approximately 14 days after onset of the disease. In liver transplantation, intraoperative
hemodynamic insults typically lead to acute renal failure which may be further worsened by
exposure to CNI therapy in the early postoperative period. In practice, patients who
demonstrate early evidence of acute renal failure often have their CNI therapy delayed for
4-5 days. This duration of CNI delay is too short to have any salutary effect on the course
or severity of acute kidney injury as less than 20% of patients experience any functional
recovery by day 5.

Thymoglobulin® (Sanofi, Cambridge, MA) is a polyclonal immunosuppressive agent that is
derived from rabbits immunized with pediatric thymocytes. It contains antibodies to a wide
variety of T-cell antigens and major histocompatibility complex (MHC) antigens and is
approved for the treatment of kidney rejection by the FDA. Thymoglobulin® has been shown to
be a safe and efficacious induction therapy that permits delayed exposure to CNI therapy
while preventing the occurrence of acute rejection in kidney transplantation. The
investigators hypothesize that any perioperative insult leading to AKI in OLT recipients is
unlikely to be beneficially impacted by a short delay of CNI introduction. Further
hypothesized is that avoidance of CNI for 10 days will have a beneficial effect on the course
and severity of perioperative AKI. Since perioperative AKI is a potent risk factor for
chronic kidney disease (CKD) in the late post-transplant period, also hypothesized is that
minimizing the risk and severity of AKI with prolonged delayed exposure to CNI will have a
beneficial effect on renal function late after liver transplantation.

Inclusion Criteria:

- Patients undergoing deceased donor solitary liver transplantation

- Age 18-75 years at the time of transplantation

- Willingness and ability to comply with the study procedures

- Signed informed consent form

- For patients with Hepatocellular carcinoma as indication for OLT, (must be within the
Milan Criteria)

- Hepatitis C, positive or negative, patients

Exclusion Criteria:

- Prior kidney transplantation

- Congenital or iatrogenic absence of one kidney

- Subjects on renal replacement therapy at the time of OLT

- MELD score >34

- HIV positive patient

- Patient with current severe systemic infection

- History of bacterial peritonitis within 30 days prior to OLT

- Active infection or recent infection within 30 days prior to OLT

- Use of a calcineurin inhibitor continuously for more than 90 days within the past 6
months

- History of hypersensitivity to Thymoglobulin®, rabbits or tacrolimus

- Pregnant and/or nursing (lactating) females.

- Women of childbearing age who are unwilling to use effective contraception during the
duration of the study, and for 30 days after study participation and/or last dose of
Study Drug.