Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation

The beneficial effects of glycemic control on both survival and function of transplanted kidneys in patients with type 1 diabetes mellitus have been recognized.

The purpose of this study is to reverse hyperglycemia and insulin dependency, by islet cell transplantation, in patients with type 1 diabetes mellitus who have a stable kidney allograft.

The study primary efficacy endpoint is graft survival defined as insulin independence and HbA1c < 8% at 1 year post first transplant. Secondary outcomes are graft function and metabolic control

The immunosuppression protocol for the kidney graft was converted to sirolimus+tacrolimus regimen 6 months before islet transplantation to exclude negative effects on kidney graft function.

Inclusion criteria

• Type 1 diabetes mellitus. Documentation of negative basal and stimulated C-peptide and diagnosis of diabetes for at least 5 years.
• Recipient of renal transplant with good function (creatinine clearance >/=60 ml/min)
• Stable immunosuppression consisting of any combination of sirolimus, tacrolimus for at least 6 months, without major complications
• Ability to give informed consent.
• Age greater than or equal to 18 years or less than or equal to 65 years
• No evidence of liver disease (liver enzymes < twice the upper limit of normal)

Exclusion criteria

• Age below 18 years and above 65 years
• Significant cardiovascular disease, including non-correctable coronary artery disease and/or recent myocardial infarction(within last 12 months); extensive peripheral vascular disease not correctable by surgery, unstable angina
• Untreated proliferative retinopathy.
• Recent Cerebrovascular accident (within last 12 months)
• Recent unresolved acute infection, or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or positive skin test for TB
• Any history of malignancy, except squamous or basal skin cancer or in situ cancer of the cervix.
• History of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin pump therapy.
• Psychiatric illness that is untreated, or likely to interfere significantly with transplantation despite treatment.
• Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures for the duration of immunosuppressive therapy
• Fasting C-peptide > 0.2 ng/ml
• Creatinine > 25mg/l
• Alkaline phosphatase, total bilirubin, Alanine Aminotransferase (ALT)or Aspartate Aminotransferase (AST) > twice the upper limit of normal
• Significant liver disease (elevation of liver enzymes > twice the upper limit of normal for each of ALT and AST, liver masses including portal vein thrombosis, evidence of portal hypertension, or significant, untreated gallbladder disease (i.e., gallstones).