Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH

The goal is to investigate the safety of the conditioning regimen, and its ability to induce donor/recipient lymphohematopoietic chimerism without Chimerism Transition Syndrome (CTS), which may result in donor-specific unresponsiveness (tolerance) to the renal allograft in the absence of maintenance immunosuppression.

Inclusion Criteria: * Male or female 18-65 years of age. * Candidate for a living-donor renal allograft from an HLA mismatched donor * Subjects with chronic kidney disease stage or ESRD who are treated with either hemodialysis or peritoneal dialysis. * First transplant. * Use of FDA-approved methods of contraception * Ability to understand and provide informed consent. * Negative COVID at screening and 2 days before procedure Exclusion Criteria: * ABO blood group-incompatible renal allograft. * Participant with a (non DSA) PRA \> 20% within 6 months prior to transplant * Persistent Leukopenia (WBC less than 2,000/mm3) or thrombocytopenia (\2 times lab normal) values for (a) liver function chemistries (ALT, AST, AP), (b) bilirubin, (c) coagulation studies (PT, PTT). * Allergy or sensitivity to any component of Siplizumab, Fludarabine, Cyclophosphamide, tacrolimus, DMSO, MMF or rituximab. * The presence of any medical condition that the investigator deems incompatible with participation in the trial. * Subjects who have non-insulin dependent diabetes (NIDDM) without good blood glucose control (HbA1c\