Inclusion Criteria:
Individuals who meet all the following criteria are eligible for enrollment as study participants:
1. Able to understand and provide informed consent
2. Agreement to use highly effective (\<1% failure rate) methods of contraception: Women of Childbearing Potential (WOCBP)-
* Progestogen only hormonal contraception associated with inhibition of ovulation,
* Hormonal methods of contraception including oral contraceptive pills containing a combination of estrogen + progesterone, vagina ring, injectables, implants and intrauterine devices (IUDs),
* Non-hormonal IUDs,
* Bilateral tubal occlusion,
* Vasectomized partner,
* Intrauterine hormone-releasing system (IUS), or
* Complete abstinence.
Note: Female participants of childbearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for 12 months while on study drug regimen.
Male Participants-
--Must use a latex or other synthetic condom during any sexual activity with WOCBP until one month after the last dose of lulizumab (e.g., up to 3.5 months in duration).
3. Recipient of primary, nonhuman leukocyte antigen identical living donor kidney transplant
4. No donor specific antibodies prior to transplant that are considered to be of clinical significance by the site investigator
5. Epstein-Barr virus (EBV) positive serology
6. Cytomegalovirus (CMV) positive serology, unless donor-recipient pair are both CMV negative
7. Negative testing for latent Tuberculosis (TB) infection within 3 months prior to transplant
* Testing should be conducted using either a purified protein derivative (PPD) or an interferon-gamma release assay blood test for TB (i.e. QuantiFERON®-TB Gold in-Tube test or T-SPOT® TB test)
* Subjects with a positive test for latent TB infection must complete appropriate therapy for Latent tuberculosis infection (LTBI). ---A subject is considered eligible only if they have a negative test for LTBI within 3 months prior to transplant or, they have appropriately completed LTBI therapy prior to transplant.
Note: Latent TB infection treatment regimens should be among those endorsed by the CDC (Division of TB Elimination, 2016).
8. In the absence of contraindication, vaccinations must be up to date for hepatitis B, influenza, pneumococcal, varicella and herpes zoster, and measles, mumps, and rubella (MMR)
9. Hepatitis C Virus (HCV) antibody positive subjects with negative HCV by PCR testing are eligible if they:
* have spontaneously cleared infection, or
* are in sustained virologic remission for at least 12 weeks after treatment for HCV.
10. Negative SARS-CoV-2 PCR test result performed within 2 weeks of transplant (SARS-CoV-2 is the virus that causes COVID-19)
Exclusion Criteria:
Individuals who meet any of these criteria are not eligible for enrollment as study participants-
1. Prisoners or subjects who are compulsorily detained
2. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
3. Candidate for a multiple solid organ or tissue transplants
4. Prior history of organ or cellular transplantation
5. Known to have idiopathic focal segmental glomerulosclerosis (FSGS) as the underlying cause of kidney failure (ESRD)
6. Requirement for uninterrupted anticoagulation therapy, including Plavix.
7. Known hypersensitivity to mechanistic target of rapamycin (mTOR) inhibitors or contraindication to everolimus (including history of wound healing complications)
8. History of severe allergic and/or anaphylactic reactions to humanized or murine monoclonal antibodies
9. Hypersensitivity to rabbit proteins or rabbit anti-thymocyte Globulin (ATG)
10. Known hypersensitivity to ACTEMRA® (tocilizumab) or lulizumab pegol (BMS-931699)
11. The human immunodeficiency virus (HIV) infected subjects, including those who are well controlled on antiretrovirals
12. Positive hepatitis B surface antigen (HBSAg), or hepatitis B core antibody (HBcAB) serology
13. Hepatitis C virus antibody positive (HCV Ab+) subjects who have failed to demonstrate sustained viral remission for more than 12 weeks after anti-viral treatment
14. Subjects with a previous history of active Tuberculosis (TB)
15. Known active current viral, fungal, mycobacterial or other infections (including, but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster)
16. Donor or recipient residing in areas where the annual incidence ≥ 21 cases per 100,000) for coccidioidomycosis according to current CDC map: (https://www.cdc.gov/fungal/diseases/coccidioidomycosis/causes.html)
* Donors or recipients residing in low risk zones (annual \<21 cases per 100,000) will not require additional screening
17. History of malignancy except treated basal cell cancer of the skin
18. History of hemolytic-uremic syndrome/ thrombotic thrombocytopenia purpura
19. History of demyelinating disorders (e.g., multiple sclerosis, chronic inflammation demyelinating polyneuropathy)
20. History of gastrointestinal perforations, active inflammatory bowel disease or diverticulitis
21. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation
22. Receipt of a live vaccine within 30 days prior to transplantation.
23. 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 participant's ability to comply with study requirements, or
* that may impact the quality or interpretation of the data obtained from the study
24. Severe hyperlipidemia (defined by total cholesterol \>350 mg/dL, LDL \>190 mg/dL, or triglycerides \>500 mg/dL)
25. Transaminase levels elevated more than 1.5 times the upper limit of normal (ULN) within 7 days prior to enrollment
26. The absolute neutrophil count (ANC) \< 2,000 per mm\^3 within 7 days prior to enrollment
27. Platelet count less than 100,000 per mm\^3 within 7 days prior to enrollment
28. More than 50% CD8+/ CD28- T-cells in peripheral blood
29. A calculated panel reactive antibody (cPRA) ≥20%, as determined by each participating site's laboratory
30. Positive pregnancy test in women of child bearing potential, currently breastfeeding, or planning to become pregnant during the timeframe of the study or follow-up period
31. Participation in any other studies with investigational drugs or regimens in the preceding year
