Inclusion Criteria for all Participants (Groups 1 and 2):
1. Provide voluntarily informed consent to participate in the study and for lifetime follow-up.
2. Have a diagnosis of ESRD at the time of informed consent.
3. Hemodialysis dependent for a minimum of 6 months and has a functioning arterial-venous fistula/graft or permanent catheter at the time of informed consent.
4. 50 to 70 years of age at the time of informed consent, or 40 to \<50 years of age with a calculated panel reactive antibody (cPRA) of ≥99.9%.
5. Evidence of thymic involution on chest computed tomography (CT) scan with a thymic region of interest score of ≤1.
6. Live within 3 hours travel time of the xenotransplant center.
7. Female participants must be postmenopausal or permanently sterilized (eg, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy). Male participants must agree to the use of a highly effective method of birth control, if the possibility of conception exists.
8. Negative xeno-crossmatch at Screening and pre-transplant.
9. Estimated Post Transplant Survival Calculator score \>20%.(https://optn.transplant.hrsa.gov/data/allocation-calculators/epts-calculator/).
10. Body mass index ≤35 kg/m2.
11. Have completed or have initiated and plan to complete (meningococcal A, C, W, Y and meningococcal B vaccine series only) Centers for Disease Control and Prevention-recommended courses of age- and risk-factor-appropriate vaccinations.
12. Seropositive (immunoglobulin G) for cytomegalovirus and Epstein-Barr virus.
Additional Inclusion Criteria for Group 1:
1\. Ineligible for conventional allogeneic kidney transplantation due to medical reason(s) for any of the following:
1. Ineligible for a living donor transplant.
2. Ineligible for an OPTN kidney transplant waitlist (reason for ineligibility will be collected).
3. Delisted from OPTN kidney transplant waitlist (reason for delisting will be collected).
Additional Inclusion Criteria for Group 2:
1. On an OPTN kidney transplant waitlist (active or inactive status).
2. No approved living kidney donors.
3. More likely to die or go untransplanted within 5 years than receive a kidney transplant as measured by the Kidney Transplant Decision Aid at the time of informed consent (select United States for "Choose your state" field and National average for "Choose your transplant program" field; https://www.srtr.org/tools/kidney-transplant-decision-aid/).
Exclusion Criteria (pertain to all participants in Groups 1 and 2):
1. Need for multiple organ transplants.
2. Severe medical co-morbidities including, but not limited to:
1. Chronic liver disease.
2. Advanced cardiovascular disease.
3. Severe peripheral vascular disease that limits technical ability to transplant the GGTA1 KO Thymokidney.
4. Severe neurologic diseases or conditions that would preclude meaningful recovery or informed consent.
5. Oral steroid-dependent airway disorder or chronic pulmonary disease or requires chronic, intermittent, or continuous supplemental oxygen.
6. Pulmonary hypertension.
7. Uncontrolled diabetes or sequelae of diabetes mellitus including severe non-proliferative diabetic retinopathy.
8. Severe neurogenic bladder that requires intermittent catheterization.
3. ESRD due to hereditary or structural kidney disease.
4. Active or recently treated malignancy at the time of informed consent.
5. Non-renal cause of hematological disorders associated with anemia (eg, thalassemia and sickle disease).
6. Cannot discontinue chronic anticoagulation therapy (low-dose daily aspirin is permissible).
7. History of major psychiatric disorders with psychiatric hospitalization and/or suicidal ideation within 5 years of informed consent.
8. Being treated for active tuberculosis (TB), have received prophylaxis for positive FDA-approved interferon-gamma release assay, or test positive for TB by FDA-approved interferon-gamma release assay test during Screening.
9. Nucleic acid test (NAT) positive for hepatitis B virus and/or hepatitis C virus, hepatitis B surface antibody (anti-HBs) titer \<10 mIU/mL unless the participant is determined to be a nonresponder to hepatitis B vaccination (a nonresponder is defined as having an anti-HB titer \<10 mIU/mL after having completed both the standard vaccine series and a fourth booster dose and/or second standard vaccine series), and/or positive for human immunodeficiency virus (HIV; HIV-1 and HIV-2 antibody and/or NAT).
10. Not able to independently perform activities of daily life.
11. Have a history of medical noncompliance that may preclude adherence to the demands and requirements of xenotransplantation (eg, history of substance use disorder \[SUD\] within 1 year of informed consent, lack of social support, untreated psychological conditions).
