Sub-Areas to Immunosuppression:
(Journal Article): Long-term Immunosuppression, Without Maintenance Prednisone, After Kidney Transplantation
Matas AJ, Kandaswamy R, Humar A, Payne WD, Dunn DL, Najarian JS, Gruessner RW, Gillingham KJ, McHugh LE, Sutherland DE (Department of Surgery, University of Minnesota, Minneapolis, MN)
IN:
Ann Surg
2004; 240(3):510-517
Impact Factor(s) of Ann Surg: 5.907 (2004), 5.937 (2003), 6.073 (2002), 6.674 (2001)
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ABSTRACT: BACKGROUND:: Concern exists that prednisone-free maintenance immunosuppression in kidney transplant recipients will increase acute and/or chronic rejection. METHODS:: From October 1, 1999, through February 29, 2004, at our center, 477 kidney transplant recipients (341 living donor, 136 cadaver) discontinued prednisone on postoperative day 6, per our protocol. Immunosuppression consisted of polyclonal antibody (Thymoglobulin) for 5 days, prednisone intraoperatively and for 5 days, a calcineurin inhibitor, and either sirolimus or mycophenolate mofetil. We compared outcome with that of historical controls who did not discontinue prednisone. RESULTS:: The recipients on prednisone-free maintenance immunosuppression had excellent 4-year actuarial patient survival (92%), graft survival (90%), acute rejection-free graft survival (86%), and chronic rejection-free graft survival (95%). The mean serum creatinine level (+/- SD) at 1 year was 1.6 +/- 0.6; at 4 years, 1.6 +/- 0.6. We noted that 8% of recipients had cytomegalovirus (CMV) disease; 4.5%, fractures; 2.8%, cataracts; 1%, posttransplant diabetes; 0.2%, avascular necrosis; 0.2%, posttransplant lymphoproliferative disease; and 0%, polyomavirus. In all, 85% of kidney recipients with functioning grafts remain prednisone-free as of April 1, 2004.As compared with historical controls, the recipients on prednisone-free maintenance immunosuppression had better patient (P = 0.02) and graft survival (P < 0.0001) and lower rates of acute (P = 0.0004) and chronic (P = 0.02) rejection. In addition, they had a significantly lower rate of CMV disease (P < 0.0001), cataracts (P < 0.0001), posttransplant diabetes (P < 0.0001), and avascular necrosis (P = 0.0003). CONCLUSIONS:: Prednisone-related side effects can be minimized without maintenance immunosuppression; our prednisone-free recipients do not have increased acute or chronic rejection.
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(Journal Article): Bcl-2 protection of islet allografts is unmasked by costimulation blockade
Sutherland RM, Allison J, Thomas HE, Brady JL, Kay TW, Lew AM (Walter and Eliza Hall Institute of Medical Research, Parkville, Australia,
kay@wehi.edu.au
)
IN:
Transplantation
2004; 77(10):1610-1613
Impact Factor(s) of Transplantation: 3.568 (2004), 3.608 (2003), 3.265 (2002), 4.184 (2001)
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ABSTRACT: One major limitation in pancreatic islet transplantation is availability of donor tissue. Donor shortage is exacerbated by islet apoptosis from the stresses of islet isolation and transplantation. Furthermore, the side effects of immunosuppressive drugs preclude transplants into patients whose diabetes is controlled by parenteral insulin. We hypothesised that over-expressing anti-apoptotic Bcl-2 or secretion of immunomodulatory CTLA4Ig molecules in islet beta cells would enhance survival of transplanted islets while minimizing systemic side effects. Over-expression of Bcl-2 neither significantly increased preservation of islet cell mass after transplantation into immunocompromised recipients nor decreased cytokine-mediated apoptosis in vitro. Although Bcl-2 over-expression alone was insufficient in protecting islet allografts from rejection, its beneficence was shown by the enhancement of protection when the adaptive immune response was inhibited by locally produced CTLA4Ig. Thus, the combination of anti-apoptotic and immunosuppressive intervention has additive or synergistic efficacy and may reduce the level of systemic immunosuppression or quantity of donor tissue required.
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