Carfilzomib and Belatacept for Desensitization

Inclusion Criteria: Individuals who meet all of the following criteria are eligible for enrollment as study subjects- 1. Subject must be able to understand and provide informed consent 2. End stage renal disease (ESRD) on dialysis 3. United Network for Organ Sharing (UNOS) listed for a kidney transplant with any one of the following: * Current calculated panel reactive antibodies (cPRA) ≥ 99.9 percent awaiting deceased donor transplant * Current cPRA \>98 percent (with \>5 years of waiting time) awaiting deceased donor transplant * Current cPRA \>98 percent with Human Leukocyte Antigen (HLA)-incompatible approved living donor and has not received a transplant after 1 year in a kidney paired exchange program 4. Evidence of established immunity to Epstein-Barr virus (EBV) as demonstrated by serologic testing 5. Negative result of most recent tuberculosis (TB) testing or appropriately completed latent tuberculosis infection (LTBI) therapy. * Testing should be conducted using either a purified protein derivative (PPD) or interferon-gamma release assay (i.e. QuantiFERON-TB, T-SPOT.TB). * Negative results from tests performed within 12 months prior to study entry are acceptable in the absence of any intervening exposure to TB. * Subjects with a positive test result must have completed appropriate therapy for LTBI. * Note: LTBI treatment regimens should be among those endorsed by the Centers for Disease Control and Prevention (CDC), url: https://www.cdc.gov/tb/topic/treatment/ltbi.htm 6. Negative Food and Drug Administration (FDA)-approved test for human immunodeficiency virus (HIV) diagnosis (at screening or as documented in medical record, up to 6 months prior to screening) 7. Negative Hepatitis C antibody test at screening or as documented in medical record, up to 6 months prior to screening. --If there is a history of treated hepatitis C then documentation of two consecutive negative HCV quantitative ribonucleic acid (RNA) polymerase chain reaction (PCR) tests separated by at least 6 months is required. Untreated subjects with positive HCV antibody and a single negative HCV quantitative HCV RNA are eligible. 8. Negative result for SARS-CoV-2 by an FDA-authorized molecular diagnostic test. Examples include, but are not limited to RT-PCR, LAMP, TMA, and qSTAR. 9. Subjects must have an echocardiogram within the previous 1 year without any of the following findings: * severe left ventricular hypertrophy (LVH) * greater than mild LVH accompanied by diastolic dysfunction * left ventricular ejection fraction \<40 percent * pulmonary hypertension defined as right ventricular systolic pressure \>35 mm Hg or tricuspid regurgitant velocity \>2.8 m/s 10. Female subjects of reproductive potential must have a negative pregnancy test upon study entry 11. All subjects of reproductive potential must agree to use contraception for the duration of the study 12. Subjects must have current vaccinations or documented immunity to: * varicella (chickenpox) * measles * hepatitis B * pneumococcus * influenza, and * varicella zoster (if ≥ 50 years old). * Note: If subjects require administration of either live or killed vaccines to meet eligibility requirements, they must wait at least 2 weeks between vaccination and the baseline visit (i.e., at least 4 weeks before initiation of therapy) Living Donor Inclusion Criteria: Living donors must meet all of the following criteria to be eligible- 1. Able to understand and provide informed consent for research 2. Meets United Network for Organ Sharing (UNOS) requirements for kidney organ donation Exclusion Criteria: Individuals who meet any of these criteria are not eligible for enrollment as study subjects- 1. Inability or unwillingness of a subject to give written informed consent or comply with study protocol 2. Known active current or history of invasive fungal infection, non-tuberculous mycobacterial infection 3. Hepatitis B surface antigen or core antibody positive 4. Serious uncontrolled concomitant major organ disease, excluding kidney failure 5. Chronic respiratory failure 6. Uncontrolled systemic hypertension 7. Previous non-kidney solid organ transplant or bone marrow transplant 8. Any infection requiring hospitalization and intravenous (IV) therapy within 4 weeks of screening or oral therapy within 2 weeks of screening 9. Primary or secondary immunodeficiency 10. History of thromboembolism (except thrombosis of dialysis vascular access site) 11. Subjects with myocardial infarction within 12 months of screening or cardiac dysrhythmias uncontrolled by medications 12. History of plasma cell dyscrasia 13. Known bleeding diathesis or coagulation abnormality 14. History of active tuberculosis (TB) (even if treated) 15. Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated cervical cancer in situ 16. Women who are currently pregnant or nursing 17. Alcohol, drug, or chemical abuse within 1 year 18. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening 19. Current treatment with other biological drug. If the potential subject receives standard of care antibody treatments for prophylaxis of COVID-19 (permitted in protocol), there must be a minimum interval of 2 weeks after this treatment and before initiation of the study therapy. 20. Current treatment with any medication which increases the risk of thromboembolic events including oral contraceptives 21. Currently smoking tobacco 22. Neutropenia (absolute neutrophil count \<1000/microliter) or thrombocytopenia (platelet count \<100,000/microliter) within 4 weeks prior to screening 23. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times upper limit of normal (ULN) or total bilirubin ≥ 2 times ULN 24. Past or current medical problems or findings from physical examination or laboratory testing not listed above, which, in the opinion of the investigator, may: * pose additional risks from participation in the study * interfere with the subject's ability to comply with study requirements, or * impact the quality or interpretation of the data obtained from the study. Exclusion Criteria for Living Donors: 1\. There are no exclusion criteria for living donors.