Islet After Kidney (IAK) Transplantation. The recent success of islet transplantation-alone for non-uremic patients has demonstrated the feasibility and practicality of the procedure using a new corticosteroid-free immunosuppressive protocol referred to as the "Edmonton Protocol".26 Individuals with type I diabetes and a successful kidney allograft are especially appropriate as candidates for a sequential islet transplant procedure because they already receive chronic immunosuppression. The added risk of a subsequent islet transplant is minimal compared to non-uremic patients with diabetes receiving new immunosuppression in addition to the transplant procedure.

Candidates for IAK transplants are distinguished from non-uremic individuals with type I diabetes in several respects. First, IAK transplant recipients may have a greater degree of diabetes-related co-morbidities such as cardio-, cerebro- and peripheral vascular diseases that preclude them from consideration of operative whole pancreas after kidney (PAK) transplantation because of excessive operative

Table 8.3. Relative contraindications for islet transplantation

Serum creatinine >1.3 mg/dL (female), >1.5 mg/dL (male) History of panel-reactive anti-HLA antibodies >20%

Negative screen for Epstein-Barr virus (EBV) by an EBV nuclear antigen (EBNA) method Active cigarette smoking (must be abstinent for 6 months)

Baseline hemoglobin <11.7 g/dL (female), <13 g/dL (male); lymphopenia (<1,000/mL), leukopenia (<3,000 total leukocytes/mL), or platelets <150,000/mL

Severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or hypersensitivity to protocol regulated treatment products

Hyperlipidemia (fasting LDL cholesterol >130 mg/dL; and/or fasting triglycerides >200 mg/dL)

Addison's disease

Current treatment for a medical condition requiring chronic use of systemic steroids risk. That is not a trivial consideration for islet transplantation since those same co-morbidities may make the "minimally" invasive radiological procedure of portal venous access and islet infusion considerably more risky in the IAK cohort than in the "healthy" ITA recipient. There simply has not been a sufficient experience with the interventional radiological experience of islet transplantation to fully understand its risk profile in patients with significant vascular diseases. Therefore, patients at prohibitive risk for surgical pancreas transplantation cannot be automatically considered for islet transplantation at this time. Consideration for islet transplantation must be made on a case-by-case basis with full informed consent of the patient of the possible risks of even the less invasive radiological procedure.

Second, recipients that have a successful kidney transplant may be prescribed an immunosuppressive regimen that differs from the corticosteroid-free protocol described by the Edmonton group. Therefore, immunosuppression conversion to the Edmonton protocol prior to islet transplantation may be required. This will be discussed in greater detail in the section covering immunosuppression.

Third, maintenance of optimal kidney transplant function becomes paramount. This difference requires consideration of treatment protocols for islet transplantation to take a backseat to those needed to maintain optimal kidney transplant function. Conflicts involving approaches to immunosuppression could appear when application of tacrolimus and sirolimus immunosuppression suited for islet transplantation unexpectedly compromises renal allograft function due to nephrotoxicity. For example, an individual who has enjoyed good and stable kidney transplant function for years while receiving cyclosporine, azathioprine and prednisone for immunosuppression is converted to tacrolimus and sirolimus at levels appropriate for the subsequent islet transplantation begins to demonstrate deteriorating renal function. In that case, it may not be possible to achieve the target levels of tacrolimus and sirolimus that have been established in the Edmonton protocol. Moving ahead with the subsequent islet transplantation in the face of

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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