Breakthrough trial aims to free kidney recipients from daily pills

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 (\<100,000/mm3). * Seropositivity for HIV-1, hepatitis B core antigen, or hepatitis C virus (confirmed by hepatitis C virus RNA); or positivity for hepatitis B surface antigen. * Active infection * Left ventricular ejection fraction \< 40% as determined by TTE or clinical evidence of heart failure * Forced expiratory volume FEV1 or DLCO \< 50% of predicted. * Lactation or pregnancy * History of cancer (following the American Transplant Society Guidelines) * Underlying renal disease etiology with a high risk of disease recurrence in the transplanted kidney (such as focal segmental glomerulosclerosis). * Prior dose-limiting radiation therapy * Known genetic disease or family history that may result in greater sensitivity to the effects of irradiation, or a physical deformity that would preclude adequate shielding or appropriate dosing during the irradiation component of the conditioning regimen * Enrollment in other investigational drug studies within 30 days prior to enrollment * Abnormal (\>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\<7). Subject with severe retinopathy, gastroparesis, or severe neuropathy which prevent subject's normal independent daily activities will be excluded from the study