Effect of Thymoglobulin Versus Basiliximab on Regulatory T Cell Function in Live Donor Kidney Transplant Recipients

This study aims to study the effects that two standard-of-care immunosuppression induction
regimens have on regulatory T cells (Treg) in live donor renal transplant recipients. These
two regimens use anti-T cell antibodies: thymoglobulin is a polyclonal anti-T cell
preparation and basiliximab is a monoclonal anti-CD25 antibody. Both are currently used in
this hospital for early immunosuppression induction but the effects on Treg numbers and
function is not well understood and may impact long term immune function. The investigators
wish to study the effects that these standard regimens have on Treg numbers, function, and
FoxP3 methylation status (an indicator of Treg function). Live donor renal transplant
patients with no panel reactive antibodies (PRA) have low risk of early allograft rejection
and in various transplant centers are treated with no anti-T cell immunosuppression induction
or induction with thymoglobulin or basiliximab as standard of care. Most patients in this
hospital receive thymoglobulin but basiliximab is used as well. There are no proven long term
benefits to either approach but each seems to lower the risk of short term acute cellular
rejection. Both of these agents have been shown to affect numbers of Tregs (as they are T
cell subsets) but data does not exist on the duration of these effects or the effects that
these agents have on Treg potency or Treg FoxP3 methylation status. Since Tregs are believed
to be important in long term control of immune responses, it is possible that the reason
these agents do not improve long term results in spite of their short term improvement in
rejection rate is due to effects on Treg.

T cell depletion by antibody has become standard of care in the majority of renal transplant
programs in the country (including Penn) and this may have reduced short term acute rejection
episodes within the first year of transplant. There have unfortunately not been corresponding
improvements in long term outcomes and, in fact, the average half life of a renal graft is
minimally changed in 2010 compared to 1995. This has been attributed to unresolved issues in
diagnosing and treating what is described as "chronic allograft nephropathy" - which in real
terms, is probably a longstanding chronic rejection that may be in part due to a mixed T and
B cell antigraft response. Despite the fact that these agents are used regularly in clinical
transplantation, little is known about their effects on regulatory T cell (Treg) numbers and
suppressive activity and nothing is known about effects on the methylation status of Tregs,
which seems to correlate with their function. These are novel questions that are a) relevant
to clinical practice since these agents are being used in renal transplantation already, b)
may yield information that could alter best practices, and c) will yield more basic
information about Tregs in human transplantation that will be relevant to future study. There
have been few papers that have looked predominantly at a few immunosuppressive agents and
numbers of Tregs (this is a low quality statistic since the markers of Tregs are shared by
other cell types and thus the "numbers" can be hard to interpret) but little about function
or methylation. The investigators propose to randomize 30 live donor kidney recipients to
receive either thymoglobulin or basiliximab immunosuppression and thereafter receive standard
of care maintenance immunosuppression determined by the clinical team. Both of these regimens
are used as standard of care in this hospital. The investigators will enroll only patients
with low immunological risk (0-10% PRA) and who are receiving an ABO compatible transplant.
After the initial randomization, all further decisions regarding immunosuppression will be
made by the clinical team independent of the study. The investigators will draw blood samples
pre-transplant, 3 months after transplant, and 6 months and 12 months after transplant.

Inclusion Criteria:

- adult patients receiving first live donor kidney transplant. 0-10% panel reactive
antibody

Exclusion Criteria:

- HIV positive, hepatitis C positive, pregnancy, inability to provide informed consent