This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function.The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.

This is a single center, randomized, controlled phase 2b, conversion trial. This protocol has been developed to answer the question: Can patients be safely converted from monthly belatacept IV infusions to abatacept subcutaneous injections without a decrease in kidney function. Research subjects will be recruited from those who were initiated on belatacept at the time of their kidney transplant and have been stable on belatacept therapy for at least 2 years post-transplant and off CNI therapy for at least 6 months.

A total of 86 subjects will be randomized in equal numbers, 43 patients in each arm. Enrollment of all 86 patients is expected to be completed within 1.5 years. All patients will be actively followed in the study for 24 months following randomization. The patient participation is projected to last a total of 3.5 years with data analysis to follow.

The primary objective will be the difference in estimated GFR (eGFR) for abatacept and belatacept groups using a monthly repeated measures model between randomization and 12 months.

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

1. Adult (age ≥18 years currently)

2. First-time renal transplant recipients of either living donor or deceased donor

   1. Treatment with belatacept from the time of transplant
   2. At least 2 years post-transplant and off CNI therapy for at least 6 months

3. Patients at low immunologic risk

   1. First time transplant
   2. HLA antibody screen with PRA < 80% against class I and class II antigens
   3. Negative crossmatch (actual or virtual)
   4. No donor specific anti-HLA antibody (DSA)
   5. No more than one episode of rejection (Banff grade 1A or greater)
   6. No episodes of rejection (borderline or greater) within the last 6 months prior to study participation
   7. No rejection of Banff grade IIB or greater

4. Immunosuppression consisting of belatacept (5mg/kg q 1M), mycophenolate mofetil (at least 1000 mg daily), or equivalent mycophenolic acid (720 mg daily) or azathioprine (1- 2 mg/kg daily) dose, and prednisone 5 mg daily.

5. Confirmed Tb screening at the time of transplantation

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for enrollment as study participants:

1. Repeat renal transplant, or multi-organ transplant recipient
2. History of more than one episode of biopsy-proven acute rejection (Banff grade 1A or greater), or of any episode of rejection of Banff 97 grade IIB or greater, or any rejection (borderline or greater) within the last 6 months
3. Pregnancy (women of childbearing potential must use adequate contraception during study)
4. GFR less than 35
5. Serum creatinine at enrollment more than 30% higher than at 3 months (±4 weeks) prior to randomization
6. Recent history of clinically significant proteinuria (urinary protein/Cr ratio >1.0)
7. Receiving belatacept at a dose other than 5 mg/kg body weight
8. Receiving mycophenolate mofetil at a dose of less than 1000 mg po QD (or mycophenolic acid or azathioprine equivalent).
9. Receiving prednisone at a dose greater than 5 mg po qd within 3 months of enrollment
10. Not currently receiving maintenance immunosuppression with prednisone
11. Active infection, or antibiotic or antiviral drug therapy within 1 month of randomization
12. Evidence of CMV viremia or clinical CMV infection within the last 3 months prior to randomization.
13. BK viremia of greater than 4.3 DNA log copies/mL (greater than 20,000 copies/mL) within 3 months of randomization
14. Known hepatitis B surface antigen-positive or PCR-positive for hepatitis B (testing not required)
15. Known HIV-positivity (testing not required)
16. Presence of donor specific antibody by Luminex single antigen bead assay, or antibody screen (% PRA) above 80%.
17. History of substance abuse or psychiatric disorder not compatible with study adherence and follow up.
18. History of medical noncompliance
19. Untreated latent Tb (as determined from prior Tb screening at the time of transplantation)

Individual participant data that underlie the results reported in this article will be shared, after de identification (text, tables, figures, and appendices) to Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose, for individual participant data meta-analysis.

Beginning 9 months and ending 36 months following article publication.

Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University&amp;amp;amp;amp;amp;amp;amp;#39;s data warehouse but without investigator support other than deposited metadata.

Individual participant data that underlie the results reported in this article will be shared, after de identification (text, tables, figures, and appendices) to Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose, for individual participant data meta-analysis.