Efficacy of Islet After Kidney Transplantation

Inclusion Criteria: * Mentally stable and able to comply with study procedures; * Clinical history compatible with type 1 diabetes with onset of disease at less than 40 years of age, insulin dependence for at least 5 years at study entry, and a sum of age and insulin dependent diabetes duration of at least 28; * Absent stimulated C-peptide (defined as less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test; * Received kidney transplant for ESRD and are taking appropriate calcineurin inhibitor (CNI) based maintenance immunosuppressive therapy; * Stable renal function as defined as creatinine of no more than one third greater than the average creatinine determination performed in the 3 previous months prior to islet transplantation, until rejection, obstruction or infection is ruled out; * Intensive diabetes management followed by reduced awareness of hypoglycemia or an HbA1c ≥ 7.5%. Exclusion Criteria: * Body mass index (BMI) greater than 30 kg/m2 or weight more than 90 kg; * Insulin requirement of \>1.0 IU/kg/day or \<15 U/day; * Other (non-kidney) organ transplants except prior failed pancreatic graft where the graft failed within the first two weeks due to thrombosis, followed by pancreatectomy and the pancreas transplant occurred more than 6 months prior to enrollment; * Untreated proliferative diabetic retinopathy; * Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg; * Calculated glomerular filtration rate of less than 40 ml/min/1.73meter-squared. More information about this criterion is in the protocol; * Proteinuria (albumin/creatinine ratio or ACr \> 300 mg/g) of new onset since kidney transplantation; * Either Class I or Class II panel-reactive anti-HLA antibodies \> 50%; Participants with either Class I or Class II panel reactive anti-HLA antibodies of 50% or less will be excluded if any of the following are detected: 1. Positive cross match; 2. Islet donor-directed anti-HLA antibodies detected my Luminex Single Antigen/specificity bead assay, including weakly reactive antibodies that would not be detected by a flow cross-match; or 3. Antibodies to the renal donor (i.e. presumed de novo). * Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion; * Active infection, including hepatitis B, hepatitis C, HIV, or tuberculosis. More information about this criterion is in the protocol. * Negative for Epstein-Barr virus (EBV) by (VCA) IgG determination; * Invasive aspergillus infection, histoplasmosis, and coccidioidomycosis infection one year prior to study enrollment; * History of malignancy except for completely resected squamous or basal cell carcinoma of the skin; * Known active alcohol or substance abuse; * History of Factor V Leiden mutation; * Any coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or individuals with an INR greater than 1.5; * Severe co-existing cardiac disease, characterized by any one of these conditions: 1. Recent MI (within past 6 months); 2. Evidence of ischemia on functional cardiac exam within the last year; 3. Left ventricular ejection fraction \< 30%; or 4. Valvular disease requiring replacement with prosthetic valve. * Persistent elevation of liver function tests at the time of study entry. Persistent serum glutamic-oxaloacetic transaminase (SGOT \[AST\]), serum glutamate pyruvate transaminase (SGPT \[ALT\],) alkaline phosphatase or total bilirubin, with values \> 1.5 times normal upper limits will exclude a subject; * Active infections (except mild skin and nail fungal infections); * Acute or chronic pancreatitis; * Active peptic ulcer disease, symptomatic gallstones, or portal hypertension; * Treatment with any anti-diabetic medication other than insulin within the past 4 weeks; * Use of any investigational agents within the past 4 weeks; * Received live attenuated vaccine(s) within the past 2 months; * Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial; * Male participants with elevation of prostate specific antigen (PSA) of more than 4 unless cancer has been excluded; * Any condition other than T1D as the primary cause of end stage renal disease (ESRD) in the native kidney; * Positive screen for BK virus by polymerase chain reaction (PCR) determination at time of screening; * A previous islet transplant; * A kidney transplant recipient with T1D who has an HbA1c \< 7.5% and no history of severe hypoglycemia.