Induction Therapy Study in Live Donor Kidney Transplant Recipients With a Positive Crossmatch

Kidney transplantation is widely recognized as the optimal therapy for the management of
end-stage renal disease. Presently, the deceased donor kidney waiting list has expanded
disproportionately with the number of transplant procedures that are performed in the United
States. To further compound this problem, as many as 1/3 of the patients on this list are
highly sensitized against a broad range of potential donors.

In order to address this problem, we developed an antibody depletion protocol that permits
transplantation in patients who have a positive crossmatch with their live donor. The
protocol consists of standard immunosuppressant therapy, plasmapheresis, and intravenous
immunoglobulin infusion. We have successfully performed transplantation in over 100 such
patients with low complication rates.

Because these patients have been exposed to their donor's human leukocyte antigen (HLA) they
are at high risk for both acute cellular and acute antibody-mediated rejection. This intent
of this prospective, randomized, open-label trial is to determine whether induction therapy
(i.e. therapy given at the time of transplantation for prophylaxis) with Thymoglobulin is
associated with a lower 6-month incidence of acute cellular and antibody-mediated rejection
than with our standard therapy, daclizumab.

Inclusion Criteria:

- Adult (18 years or older)

- End-stage renal disease

- Identified to have positive lymphocytotoxic crossmatch or flow cytometric crossmatch
with live donor

Exclusion Criteria:

- Deceased donor recipients

- Pregnancy

- Active infection

- History of cancer within the past two years (with the exception of non-melanomatous
skin cancer)

- History of heparin induced thrombocytopenia

- Medical contraindications to transplant procedure