Optimum Immunosuppression in Renal Transplant Recipients.New Onset Diabetes After Transplantation

Optimum Immunosuppression in Renal Transplant Recipients at High Risk of Developing New Onset Diabetes After Transplantation: A Multicenter, Prospective, Controlled and Randomized Trial.

New onset diabetes after renal transplantation (NODAT) is a common and severe complication negatively influencing graft and patient survival. Cyclosporine (CsA) and Tacrolimus are the basis of modern immunosuppression. Tacrolimus is superior to CsA in terms of acute rejection and graft function. However, Tacrolimus increases 2 times the risk of NODAT as compared to CsA.

New onset diabetes after renal transplantation (NODAT) is a common and severe complication negatively influencing graft and patient survival. CsA and Tacrolimus are the basis of modern immunosuppression. Tacrolimus is superior to CsA in terms of acute rejection and graft function. However, increases 2 times the risk of NODAT as compared to CsA. Objectives: a) To compare the incidence of NODAT and glucose intolerance with 3 different regimes: Tacrolimus with rapid steroid withdrawal; Tacrolimus with steroids minimization; and CsA with steroid minimization; b) To compare acute rejection rate, renal function and graft and patient survival between different regimes; and c) to investigate the influence of different regimes on subclinical atheromatosis. A total of 210 patients will be randomized. The primary efficacy variable will be NODAT or glucose intolerance at 1 year; secondary efficacy variables will be acute rejection, renal function, and changes of carotid intima-media thickness over time.

Inclusion Criteria:

• Primary renal transplant recipients with end stage renal disease
• No prior history of diabetes mellitus before transplant
• Absence of Immunologic risk defined by the investigator criterion and Panel Reactive Antibody (PRA) < 50%
• Absence of severe infection and hepatitis C or B infection
• Efficient contraception in women during the study

Additionally must meet one of these "Metabolic Criteria

• Recipient age >or =60 or
• Recipient age between 45 and 59 years and at least one of the following metabolic criteria: Prior to transplantation Triglycerides (TGS) >200mg/dl or the combination of a body mass index (BMI)> 27 and Triglycerides>150 mg/dl or the combination of HDL-cholesterol<40 mg/dl for men or <50 mg/dl for women and Triglycerides >150 mg/dl.

Exclusion Criteria:

• Patients with type I or II diabetes prior to transplantation defined by the American Diabetes Association (ADA) criteria
• Recipient age under 45
• Patients receiving a second renal transplant
• Patients with high immunological risk or PRA (panel reactive antibody level) >or =50%
• Severe infection or hepatitis C or B infection.
• Dual renal transplant or double transplant with any other organ.