This proposal's objective is to determine whether belatacept, in conjunction with a proteasome inhibitor can be used to safely increase the likelihood of finding an acceptable donor for highly HLA sensitized kidney transplant candidates.

This is a pilot study to test the safety and effectiveness of the desensitization therapy with belatacept and proteasome inhibitor to increase the likelihood of of finding an acceptable donor for highly HLA sensitized kidney transplant candidates.

Inclusion Criteria:

• Highly sensitized patient cPRA 99-100% AND actively listed for kidney transplantation at the kidney transplantation Program at University fo Chicago
• Ebstein Barr Virus (EBV) Immunoglobulins (IgG) seropositive
• No active systemic infection
• No allergy to proteasome inhibitors (Bortezomib), or to belatacept
• No known malignancy in the previous 2 years except for non-melanomatous skin cancer
• Female who agrees to practice 2 effective methods of contraception through 3 months after the last dose of Bortezomib
• Patient vaccinated against hepatitis B virus with positive level of HBsAb
• Patients fully vaccinated against Coronavirus Disease 2019 at least 2 weeks prior to the start of the 1st cycle.
• Actively listed for kidney transplant at the Transplant Institute at University of Chicago

Exclusion Criteria:

• Patient with significant neuropathy by the Common Terminology Criteria for Adverse Events (CTCAE) criteria within 14 days before enrollment (Grades 3-4 or Grade 2 with pain)
• Myocardial infarction within 6 months of enrollment or has Heart Failure in acute dialysis quality initiative (ADQI) ESRD classification system Class 2 non restrictive (2NR) or greater, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia or active conduction system abnormalities
• Patient who received other investigational drugs within 14 days prior to initiation of study treatment
• Receipt of a live vaccine within 4 weeks prior to initiation of study treatment
• Evidence of severe liver disease by history or physical exam or with abnormal liver profile ( > 1.5 times upper limit of normal within 30 days of consent)
• Female who is breast feeding or pregnant
• Untreated latent tuberculosis
• History of Post Transplant Lymphoproliferative Disease (PTLD)
• Patient still carrying previous kidney transplant.