Medication Summary
All pancreas transplant recipients require lifelong immunosuppression to prevent a T-cell alloimmune rejection response. The US Food and Drug Administration (FDA) has approved several immunosuppressive agents; others are used off label, and additional agents are currently in clinical trials.
Two broad categories of immunosuppressive agents exist: intravenous induction/antirejection agents and maintenance immunotherapy agents. No consensus exists as to the single best immunosuppressive protocol, and each transplant program utilizes various combinations of agents slightly differently.
The goals are to prevent acute or chronic rejection, minimize drug toxicity, minimize rates of infection and malignancy, and achieve the highest possible rates of patient and graft survival.
Immunosuppressant agents for induction immunotherapy
Class Summary
Induction immunotherapy consists of a short course of intensive treatment with intravenous agents. Antilymphocyte antibody induction therapeutic agents include polyclonal antisera, monoclonal antibodies, and humanized monoclonals. Polyclonal antisera, such as antilymphocyte globulin (ALG), antilymphocyte serum (ALS), and anti-thymocyte globulin (ATG) are equine, goat, or rabbit antisera directed against human lymphoid cells. These significantly lower and almost abolish circulating lymphoid cells critical to rejection response.
The agents are very effective at prophylaxis against early acute rejection, which is especially beneficial in managing the recipient with delayed graft function. The agents provide an effective immunologic cover during a period where the calcineurin inhibitors are either delayed or administered in subtherapeutic doses until graft function improves. Induction agents are used less often if immediate graft function occurs, such as recipients of living kidney donors, especially HLA-identical grafts.
Basiliximab (Simulect)
A chimeric monoclonal antibody that specifically binds to and blocks the interleukin-2 (IL-2) receptor on the surface of activated T cells.
Antithymocyte globulin, rabbit (Thymoglobulin)
A purified immunoglobulin solution produced by the immunization of rabbits with human thymocytes is used to treat acute rejection.
Alemtuzumab (Campath)
A humanized monoclonal antibody against the CD52 antigen. The anti-CD52 antibody induces lympholysis from complement-mediated lysis or other effector mechanisms.
Maintenance immunosuppression agents
Class Summary
Several immunosuppressive agents are currently used for maintenance immunotherapy in kidney transplant recipients. An optimal maintenance immunosuppressive protocol has not been developed. Maintenance immunosuppressive agents are required for life.
Prednisone
Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.
Azathioprine (Imuran)
The active component of azathioprine is 6-mercaptopurine. It acts as a purine analog that interacts with DNA and inhibits lymphocyte cell division.
Mycophenolate (CellCept, Myfortic)
Inhibitor of enzyme inosine monophosphate dehydrogenase (IMPDH), which results in inhibition of lymphocyte proliferation. Approved for prevention of organ rejection in allogeneic renal allograft recipients, and used off-label in patients with pancreas transplants.
Cyclosporine (Sandimmune, Neoral)
Calcineurin inhibitor that diminishes IL-2 production in activated T cells. It binds to the intracellular immunophilin cyclophilin, interfering with the action of calcineurin, which inhibits nuclear translocation of the nuclear factor of activated T cells (NFAT).
Tacrolimus (Prograf)
Calcineurin inhibitor that diminishes IL-2 production in activated T cells. Binds to intracellular immunophilin, FKBP, interfering with the action of calcineurin, which inhibits nuclear translocation of the NFAT. FDA approved for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.
Sirolimus (Rapamune)
Inhibits lymphocyte proliferation by interfering with signal transduction pathways. Binds to immunophilin FKBP to block the action of mTOR. FDA approved for the prevention of organ rejection in patients receiving allogeneic renal allografts.
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Simultaneous pancreas-kidney transplantation with enteric drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.
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Solitary pancreas transplantation with enteric drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.
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Solitary pancreas transplantation with bladder drainage. Illustrated by Simon Kimm, MD. Image courtesy of Landes Bioscience.
Tables
Patient Characteristic |
All Candidates |
PAK | PTA | SPK | ||||
| Number | PCT | Number | PCT | Number | PCT | Number | PCT | |
Age 18-34 y |
226 |
22.7% |
4 | 9.1% | 20 | 24.7% | 202 | 23.2% |
Age 35-49 y |
520 |
52.3% |
30 | 68.2% | 34 | 42.0% | 520 | 52.3% |
Age 50-60 y |
213 |
21.4% |
9 | 20.5% | 20 | 24.7% | 213 | 21.4% |
Age > 60 y |
35 |
3.5% |
1 | 2.3% | 7 | 8.6% | 27 | 3.1% |
Male |
606 |
61.0% |
26 | 59.1% | 37 | 45.7% | 543 | 62.5% |
Female |
388 |
39.0% |
18 | 40.9% | 44 | 54.3% | 326 | 37.5% |
White |
519 |
52.2% |
27 | 61.4% | 66 | 81.5% | 426 | 49.0% |
Black |
271 |
27.3% |
8 | 18.2% | 9 | 11.1% | 254 | 29.2% |
Hispanic |
157 |
15.8% |
7 | 15.9% | 6 | 7.4% | 144 | 16.6% |
Asian |
43 | 4.3% |
2 | 4.5% | 0 | 0% | 41 | 4.7% |
| Other | 4 | 0.4% | 0 | 0% | 0 | 0% | 4 | 0.5% |
| All recipients | 1015 | 100% | 44 | 4% | 99 | 10% | 872 | 86% |
