Selective CD28 Blockade in Renal Transplant Recipients

Inclusion Criteria: Individuals who meet all of the following criteria are eligible for enrollment as study participants: 1. Must be able to understand and provide informed consent; 2. Negative crossmatch (actual or virtual) or a Panel Reactive Antibody (PRA) of 0% on historic and admission sera; 3. First time renal transplant from either a living or deceased donor; 4. Deceased donor recipients only: Deceased donor kidneys with Kidney Donor Profile Indices (KDPI) \<85%; 5. Female study participants of childbearing potential must have a negative pregnancy test prior to randomization; 6. Agreement to use contraception; according to the Food and Drug Administration (FDA) Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80 percent effective. --Female study participants of child-bearing potential and male study participants must consult with their physician and determine the most suitable method(s) from this list to be used from the time that study treatment begins until after study completion; 7. Study participants must have a negative purified protein derivative (PPD) or negative testing for tuberculosis using an approved interferon-gamma release assay (IGRA) blood test, such as: * QuantiFERON®-TB Gold In-Tube test (QFT-GIT) or * TSPOT® TB test ---PPD or IGRA testing must be documented to have been performed within 52 weeks before transplant; 8. Documented completion of varicella vaccination series ≥ 8 weeks prior to enrollment, OR verification of a history of varicella or zoster by a physician OR positive laboratory confirmation of varicella immunity or disease; and, 9. Immunizations are up-to-date based on the CDC° adult vaccination recommendations: https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html --°Centers for Disease Control and Prevention (CDC) Exclusion Criteria: Individuals who meet any of these criteria are not eligible for enrollment as study participants: 1. Inability or unwillingness of a study participant to give written informed consent or comply with study protocol; 2. Recipient of previous organ transplant of any type; 3. Need for multi-organ transplant; 4. Calculated panel reactive antibody (cPRA) or panel reactive antibody (PRA) \>20% at any time prior to enrollment; 5. Known hypersensitivity to mycophenolate mofetil (MMF) or any of the drug's components; 6. Human immunodeficiency virus (HIV): individuals known to be HIV positive; 7. Known history of Bacillus Calmette-Guérin (BCG) vaccination; 8. Individuals at significant risk of early recurrence of the primary renal disease including: -Focal Segmental Glomerulosclerosis (FSGS) * Membranoproliferative Glomerulonephropathy (MPGN) type 2 * Hemolytic Uremia Syndrome/Thrombotic thrombocytopenic purpura (HUS/TTP), or * any other disease that, in the opinion of the investigator, is at increased likelihood of recurrence and which may result in rapid decline in renal function 9. Known history of high-risk thrombotic events or risk factors; including any of the following: * Factor V Leiden, elevated homocysteine, positive lupus anticoagulant, elevated anticardiolipin antibody, heparin induced thrombocytopenia * A family history of a heritable thrombotic condition * Recurrent Deep vein thrombosis (DVT) or Pulmonary Embolism (PE), or * Unexplained stillborn infant or recurrent spontaneous abortion of other congenital or acquired thrombotic disorder 10. History of malignancy within 5 years of enrollment or any history of hematogenous malignancy or lymphoma. --Note: Study participants with curatively treated non-melanomatous skin cancer or curatively treated cervical carcinoma in situ may be enrolled; 11. Study participants who are on biologic treatments for autoimmune disease; 12. Study participants who are involuntarily detained (e.g. prison, jail, compulsory psychiatric or medical therapy); 13. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator: * May pose additional risks from participation in the study, * May interfere with the study participant's ability to comply with study requirements, or * May impact the quality or interpretation of the data obtained from the study; 14. Human leukocyte antigen (HLA) identical donor/recipient pairing; 15. Use of investigational drugs within 4 weeks of transplant; 16. Study participants who are NOT Epstein-Barr virus (EBV) seropositive -A prior documented EBV seropositive result at enrollment does not need to be repeated --For this study, EBV seropositive patients are defined as having evidence of acquired immunity shown by the presence of immunoglobulin G (IgG) antibodies to viral capsid antigen (VCA) and the presence of antibodies to EBV nuclear antigen (EBNA or EBNA1); 17. Hepatitis C virus (HCV): Study participants who are HCV RNA PCR positive at prerandomization re-evaluation -Study participants who are seropositive must have 2 consecutive negative HCV RNA PCR at least 24 weeks apart; 18. Hepatitis B virus: Individuals with any of the following are NOT eligible: * Recipient or donor positive for hepatitis B surface antigen (HBsAg) * Recipient or donor with antibodies to hepatitis B core antigen (anti-HBc) * Recipient or donor with HBV DNA detectable by PCR; 19. Recipient of a live or live-attenuated vaccine within 8 weeks prior to transplant; 20. Cytomegalovirus (CMV) seronegative individuals accepting an organ from a CMV seropositive donor; 21. Study participants undergoing transplant using: * Organs from donation after circulatory death (DCD) donor * Donor with Kidney Donor Profile Index (KDPI) \>85%, or * Anticipated cold ischemia time \>28 hours; or, 22. ABO incompatible donor kidney.