Immunological Tolerance in Patients With Mismatched Kidney Transplants

Exclusion Criteria

• •1. ABO incompatibility with donor
• •2. Previous solid organ transplant
• •3. Multi-organ transplantation
• •4. Previous treatment with rATG or a known allergy to rabbit proteins
• •5. Previous treatment with belumosudil (KD025)
• •6. History of active malignancy within the past 5 years with the exception of:
• •1. Low risk cancer on active surveillance
• •2. Malignancy treated with curative intent with no known active disease \>2 years before the first dose of study treatment and of low potential risk of recurrence
• •3. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• •4. Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ, and DCIS)
• •7. Pregnant (confirmed by urine or serum pregnancy test) or lactating
• •8. Leukopenia (with a white blood cell count \< 3,000/µL) or thrombocytopenia (with a platelet count \< 100,000/µL)
• •9. INR and/or PTT ≥ 1.5X upper limits of institutional normal
• •10. Positive HLA DSA
• •11. Active bacterial, fungal, mycobacterial, or viral infection (including active hepatitis B and/or C, or West Nile Virus)
• •12. Seropositivity for HIV 1, HIV 2, HTLV-1 or HTLV-II
• •13. Renal disease with high risk of recurrence (i.e., focal segmental glomerulosclerosis)
• •14. Advanced hepatic fibrosis or cirrhosis
• •15. Congestive heart failure, symptomatic coronary artery disease, and/or uncontrolled cardiac arrhythmia
• •16. Active extra-renal autoimmune disease requiring immunosuppression
• •17. Neuropsychiatric or medical illness that precludes the ability to give informed consent and/or places the patient as high risk for non-compliance with the safety monitoring requirements of the study
• •18. May not have received immunosuppressive medications within one year of the study treatment. Use of corticosteroids prescribed for a time-limited indication (\</= 4 weeks) and stopped at least 4 weeks before the kidney transplant is acceptable.
• •19. May not have received immunotherapy or immunomodulatory drugs such as immune checkpoint inhibitors, tumor necrosis factor inhibitors, rituximab, intravenous immune globulin, and interleukin-2 within one year of the study treatment
• •20. Current or active abuse of alcohol and/or drugs within the last 6 months
• •21. Body Mass Index (BMI) ≥ 40
• •22. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• •23. ESRD patients with the following etiologies
• •1. Autoimmune disease including lupus
• •2. Vasculitis involving the kidney (such as Wegener's Granulomatosis
• •3. Thrombotic Thrombocytopenic Purpura
• •4. Alport's syndrome (due to increased risk of developing post-transplant Anti-Glomerular Basement Membrane Disease (Anti-GBM Disease))
• •24. HgbA1c ≥10
• •25. Prior history of radiation therapy
• •26. History of ≥ 20 pack per year smoking. a. Patients must be abstinent from tobacco use for ≥ 6 months prior to transplantation
• •1. ABO incompatibility with recipient
• •2. Medically unfit to tolerate peripheral blood apheresis (small body size, poor vascular access, not a suitable candidate for placement of a central catheter, etc.)
• •3. Pregnant (confirmed by urine or serum pregnancy test) or lactating
• •4. Seropositivity for HIV 1, HIV 2, HTLV-I or HTLV-II
• •5. Active bacterial, fungal, mycobacterial or viral infection (including active hepatitis B and/or C, West Nile Virus)
• •6. Psychiatric, addictive, neurological, or other disorder that compromises ability to give true informed consent for participation in this study
• •7. History of active malignancy within the past 5 years with the exception:
• •1. Adequately managed malignancy within the past two years with low risk of recurrence may be acceptable as per clinician discretion
• •2. Adequately managed non-melanoma skin cancer
• •3. Adequately managed carcinoma in situ e.g., cervical cancer in situ, and DCIS
• •8. No current or recent use of oral anti-coagulants. (For the purpose of this study, recent is defined as less than 60 days prior to apheresis). Aspirin and non-steroidal anti-inflammatory drugs must be stopped 14 days prior to apheresis.
• •9. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data