Renal Allograft Tolerance Through Mixed Chimerism (Belatacept)

Inclusion Criteria:

- Male or female 18-60 years of age

- Candidate for a living-donor renal allograft from an HLA mismatched donor

- First or second transplant with either a living donor or cadaveric transplant as the
first transplant.

- Use of FDA-approved methods of contraception by all recipients from the time that
study treatment begins until 104 weeks (24 months) after renal transplantation.

- Ability to understand and provide informed consent.

- Serologic evidence of prior exposure to EBV.

Exclusion Criteria:

- ABO blood group-incompatible renal allograft.

- Evidence of anti-HLA antibody within 60 days prior to transplant as assessed by
routine methodology (AHG and/or ELISA)

- Leukopenia or thrombocytopenia.

- Positive for HIV-1, hepatitis B core antigen, or hepatitis C virus; or positivity for
hepatitis B surface antigen.

- Cardiac ejection fraction < 40% or clinical evidence of insufficiency.

- Forced expiratory volume FEV1 < 50% of predicted.

- Lactation or pregnancy.

- History of cancer other than basal cell carcinoma of the skin or carcinoma in situ of
the cervix.

- Underlying renal disease etiology with a high risk of disease recurrence in the
transplanted kidney (such as focal segmental glomerulosclerosis, type I or II
membranoprolifertive glomerulonephritis).

- Prior dose-limiting radiation therapy.

- Known genetic disease or family history that may result in greater sensitivity to the
effects of irradiation, or a physical deformity that would preclude adequate shielding
or appropriate dosing during the irradiation component of the conditioning regimen.

- Enrollment in other investigational drug studies within 30 days prior to enrollment.

- Abnormal (>2 times lab normal) values for (a) liver function chemistries (ALT, AST,
AP), (b) bilirubin, (c) coagulation studies (PT, PTT).

- Allergy or sensitivity to any component of belatacept, ATG, tacrolimus, or rituximab.

- Maintenance immunosuppression within 3 months prior to conditioning other than
physiological doses of steroids, defined as ≤ 50 mg of hydrocortisone or dose
equivalent.

- The presence of any medical condition that the investigator deems incompatible with
participation in the trial.