%0 Journal Article
%T Perioperative Minimal Induction Therapy: A Further Step toward More Effective Immunosuppression in Transplantation
%A Alessia Gennarini
%A Paolo Cravedi
%A Maddalena Maras¨¤
%A Annalisa Perna
%A Giovanni Rota
%A Mario Bontempelli
%A Silvio Sandrini
%A Giuseppe Remuzzi
%A Piero Ruggenenti
%J Journal of Transplantation
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/426042
%X Dual induction with low doses of rabbit anti-human thymoglobulin (RATG) and basiliximab effectively and safely prevented allograft rejection in high-risk renal transplant recipients. To assess whether treatment timing affects efficacy and tolerability, in this single-center, matched-cohort study, we compared posttransplant outcomes in 25 patients and 50 gender-, age-, and treatment-matched reference patients induced with the same course of 7 daily RATG infusions (0.5£¿mg/kg/day) started before or after engraftment, respectively. All subjects received basiliximab (20£¿mg) before and 4 days after transplantation, withdrew steroids within 6 days after surgery, and were maintained on steroid-free immunosuppression with cyclosporine and mycophenolate mofetil or azathioprine. Over 12 months after transplant, 1 patient (4%) and 13 reference patients (26%) had acute rejection episodes. One patient and 5 reference-patients required dialysis therapy because of delayed graft function. In all patients circulating CD4+ and CD8+ T lymphocytes were fully depleted before engraftment. Both treatments were well tolerated. In kidney transplantation, perioperative RATG infusion enhances the protective effect of low-dose RATG and basiliximab induction against graft rejection and delayed function, possibly because of more effective inhibition of early interactions between circulating T cells and graft antigens. 1. Introduction Induction therapy with early administration of antilymphocyte antibodies has been introduced into clinical transplantation to modify the host immune response at the time of donor antigen presentation. This approach is aimed at achieving immune hyporesponsiveness of the host expected to translate into a reduced risk of rejection in the posttransplant period [1, 2]. Different antibodies have been used for induction therapy, including monoclonal nondepleting antibodies such as basiliximab and daclizumab, and monoclonal or polyclonal depleting antibodies, such as alemtuzumab or thymoglobulin, respectively [1, 2]. Nondepleting are safer than depleting antibodies, but are less effective [3]. Depleting antibodies may cause severe adverse events including infusion-related cytokine-release syndrome and enhanced risk of CMV reactivations and lymphoproliferative disorders in the long term [4, 5]. To minimize side effects, we introduced in our clinical practice an induction strategy based on rabbit anti-human thymoglobulins (RATGs) administered at very low doses (approximately half the currently recommended doses for induction and one-third to one-fourth of doses
%U http://www.hindawi.com/journals/jtrans/2012/426042/