A Trial of Tolerogenic Immunosuppression in Highly Sensitized Renal Transplant Recipients

Recent reports suggest that it might be possible to induce a state of tolerance in solid
organ transplantation. So called "tolerogenic immunosuppression" involves induction with
lymphocyte depleting antibodies followed by monotherapy with calcineurin inhibitors,
cyclosporin or tacrolimus. The proposed study aims to evaluate a protocol of
immunosuppression induction with lymphocyte depleting antibody Campath given prior to graft
reperfusion, followed by tacrolimus monotherapy in highly sensitized patients (PRA >14% or
past historical =/>50% and/or multiple renal transplants) undergoing renal transplantation,
and compare it with the current standard protocol at UTMB which employs induction with
Thymoglobulin given over 4 days followed by 3 drugs: tacrolimus, mycophenolate and steroids.
In both groups of patients the target tacrolimus levels will be the same i.e, between 10 to
15ng/mL, soon after the transplant. In the Campath gro up, tacrolimus will be tapered after 3
months in patients who do not have rejection and appear to be developing donor specific
tolerance.

Inclusion Criteria:

1. Males and females aged 18-75 years.

2. Recipients of multiple kidney transplants

3. Patients with a PRA >14% and/or a past historical PRA greater or equal to 50%.

4. Females of childbearing potential must have a negative pregnancy test prior to
inclusion.

5. Patients who are willing and able to participate in the full course of the study and
from whom written informed consent has been obtained.

Exclusion Criteria:

1. Patients with a history of malignancy within the last 5 years, except excised squamous
or basal cell carcinoma of the skin.

2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after contraception and until the termination of gestation,confirmed by a
positive human chorionic gonadotropin(hCG) laboratory test.

3. Patients who are HIV positive.

4. Patients with symptoms of significant somatic or mental illness or evidence of current
drug and/or alcohol abuse.