TY - JOUR
T1 - Immunosuppression in simultaneous pancreas-kidney transplantation
T2 - Progress to date
AU - Heilman, Raymond L.
AU - Mazur, Marek J.
AU - Reddy, K. Sudhakar
N1 - Funding Information:
No sources of funding were used to assist in the preparation of this review. Dr Heilman has received research grants from Genzyme Corporation and Wyeth Corporation. Drs Mazur and Reddy have no conflicts of interest that are directly relevant to the content of this review.
PY - 2010
Y1 - 2010
N2 - Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with end-stage renal failure due to type 1 diabetes mellitus. With advances in surgical techniques and immunosuppression management, outcomes have improved, with current 1-and 10-year pancreas graft survival rates of 86 and 53, respectively. Induction therapy with either alemtuzumab or rabbit antithymocyte globulin (rATG) in combination with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) or sirolimus appears to be safe and effective in the setting of rapid steroid withdrawal (RSW), with excellent graft survival and low rejection rates. There are no large randomized trials between alemtuzumab and rATG to determine whether one is better than the other. Anti-interleukin (IL)-2 receptor antibody induction and no induction in combination with a CNI, MMF or sirolimus, and prednisone have demonstrated excellent graft survival rates but are associated with a higher incidence of acute rejection. The efficacy of anti-IL-2 receptor antibodies or no induction in the setting of RSW is unproven. Both of the CNIs, ciclosporin and tacrolimus, are effective in preventing acute rejection in SPKT recipients; however, pancreas allograft survival may be better with tacrolimus. MMF is more effective than azathioprine in preventing acute rejection. Sirolimus appears to be effective in preventing acute rejection, but the combination of sirolimus with a CNI may accentuate the nephrotoxicity of the CNI. RSW with induction therapy is safe and effective in SPKT recipients, but longer follow-up data on outcomes are needed. Recent analysis of registry data shows that most transplant centres are using an induction agent followed by a combination of tacrolimus, MMF and corticosteroids in SPKT recipients.
AB - Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with end-stage renal failure due to type 1 diabetes mellitus. With advances in surgical techniques and immunosuppression management, outcomes have improved, with current 1-and 10-year pancreas graft survival rates of 86 and 53, respectively. Induction therapy with either alemtuzumab or rabbit antithymocyte globulin (rATG) in combination with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) or sirolimus appears to be safe and effective in the setting of rapid steroid withdrawal (RSW), with excellent graft survival and low rejection rates. There are no large randomized trials between alemtuzumab and rATG to determine whether one is better than the other. Anti-interleukin (IL)-2 receptor antibody induction and no induction in combination with a CNI, MMF or sirolimus, and prednisone have demonstrated excellent graft survival rates but are associated with a higher incidence of acute rejection. The efficacy of anti-IL-2 receptor antibodies or no induction in the setting of RSW is unproven. Both of the CNIs, ciclosporin and tacrolimus, are effective in preventing acute rejection in SPKT recipients; however, pancreas allograft survival may be better with tacrolimus. MMF is more effective than azathioprine in preventing acute rejection. Sirolimus appears to be effective in preventing acute rejection, but the combination of sirolimus with a CNI may accentuate the nephrotoxicity of the CNI. RSW with induction therapy is safe and effective in SPKT recipients, but longer follow-up data on outcomes are needed. Recent analysis of registry data shows that most transplant centres are using an induction agent followed by a combination of tacrolimus, MMF and corticosteroids in SPKT recipients.
KW - Alemtuzumab, therapeutic use
KW - Antithymocyte-globulin, therapeutic use
KW - Basiliximab, therapeutic use
KW - Ciclosporin, therapeutic use
KW - Daclizumab, therapeutic use
KW - Kidney-pancreas-transplant
KW - Kidney-pancreas-transplant-rejection
UR - http://www.scopus.com/inward/record.url?scp=77951706606&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951706606&partnerID=8YFLogxK
U2 - 10.2165/11535430-000000000-00000
DO - 10.2165/11535430-000000000-00000
M3 - Review article
C2 - 20426494
AN - SCOPUS:77951706606
SN - 0012-6667
VL - 70
SP - 793
EP - 804
JO - Drugs
JF - Drugs
IS - 7
ER -