Treatment Of Rejection In Renal Transplantation Research Articles

Safety and Long-Term Efficacy of Sirolimus-Eluting Stents

Sirolimus was isolated in 1975 and was initially approved for the treatment of renal transplant rejection. The main mechanism of action is mTOR inhibition, which prevents cell cycle progression. The first-in-human study of the sirolimus-eluting stent (SES) was initiated in 1999 in Sao Paulo Brazil and Rotterdam. The study demonstrated a reduction in restenosis after SES implantation when compared with bare-metal stents. The first approved drug-eluting stent was the SES Cypher®. Several modifications in stent platform and polymer coating have been made, in an effort to improve deliverability and to reduce inflammatory response secondary to nonbiocompatible polymers. Bioabsorbable polymer and polymer-free technologies are the main characteristic of the second- and third-generation SES. Larger studies with longer follow-up are needed to prove the efficacy of those stents when compared with previous platforms.

Off‐label use of rituximab in a tertiary Queensland hospital

Rituximab is a monoclonal antibody directed against CD20, a pan B lymphocyte marker. It is approved in Australia for treatment of CD20-positive B cell non-Hodgkin lymphoma and rheumatoid arthritis. There is increasing off-label use of rituximab in conditions where B cells and autoantibodies play a role in the pathophysiology. Rituximab is not only expensive, but its safety in unregistered indications is uncertain. We performed a retrospective review of the off-label use of rituximab approved by the High Cost Drug Subcommittee at the Princess Alexandra Hospital between 2005 and 2008. Cases of post transplant lymphoproliferative disorder were excluded. A total of 28 patients received rituximab for a variety of off-label indications. There were no reported cases of serious infusion reactions or other notable adverse events. The most favourable outcomes were seen in myasthenia gravis, shrinking lung syndrome, thrombotic thrombocytopenic purpura, prevention and treatment of renal transplant rejection and lupus nephritis. No benefit was observed in cases of focal segmental glomerulosclerosis (primary or post-transplant recurrence) and post-transplant recurrence of haemolytic uremic syndrome. There was limited benefit in cryoglobulinaemic vasculitis. The cost of off-label use was in excess of $210,000. In the absence of formal clinical trials, decisions regarding off-label use of rituximab are difficult. Our cases contribute to the published literature and should help provide clinicians with greater insights into which conditions are likely to respond. As can be seen in our series, rituximab benefits people with certain conditions; longevity and cost-effectiveness are currently unknown.

Rabbit Antithymocyte Globulin (Thymoglobulin®)

Rabbit antithymocyte globulin (rATG) [Thymoglobulin(R); Thymoglobuline(R)] is a purified, pasteurized preparation of polyclonal gamma immunoglobulin raised in rabbits against human thymocytes that is indicated for the prevention and/or treatment of renal transplant rejection in several countries worldwide. rATG induction in combination with immunosuppressive therapy is more effective in preventing episodes of acute renal graft rejection in adult renal transplant recipients than immunosuppressive therapy without induction. The efficacy of rATG induction is generally better than that of equine antithymocyte globulin (eATG) induction and generally no different from that of basiliximab or low-dose daclizumab induction in this patient population. However, in high-risk patients, rATG induction was more effective than daclizumab or basiliximab induction in preventing acute renal graft rejection. In the treatment of renal graft rejection in adult renal transplant recipients, rATG was more effective than eATG in terms of the successful response rate, although the agents generally did not differ with regard to most other endpoints. Both induction and treatment with rATG are generally well tolerated, although adverse events, such as fever, leukopenia and thrombocytopenia, appear more common with rATG than with other antibody preparations. The overall incidence of infection associated with rATG induction was generally no different from that seen with eATG or basiliximab induction, although was higher with rATG than with basiliximab in high-risk patients. The incidence of cytomegalovirus (CMV) disease generally did not differ between rATG and eATG induction, and there was no significant difference between rATG and daclizumab induction with regard to the incidence of CMV infections or the proportion of patients who received treatment for a CMV episode or infection. Relative to basiliximab, the incidence of CMV infection was generally higher with rATG, except in high-risk patients. In the treatment of acute renal rejection, the nature and incidence of infections were generally similar with rATG and eATG. The incidence of malignancies is generally low with rATG therapy and generally does not differ from that seen with other agents. Further prospective comparative studies would be beneficial in order to definitively position rATG with respect to other antibody preparations. In the meantime, available clinical data suggest that rATG is an effective and generally well tolerated option for the prevention and treatment of acute renal graft rejection in renal transplant recipients.

New trends in transplantation: the use of Thymoglobulin®

Background: Thymoglobulin® (Genzyme Co., Cambridge, MA, USA), rabbit anti-thymocyte globulin, is an immunosuppressive drug approved for the treatment of renal transplant rejection. Objective: To review the pharmacology, toxicity and efficacy of Thymoglobulin in solid organ and stem cell transplantations. Methods: Review of the literature, information from Genzyme and personal clinical trial experience serve as sources for this review. Conclusion: Thymoglobulin has helped to facilitate the growth of successful steroid sparing approaches to solid organ transplantation. Thymoglobulin is now incorporated into several stem cell transplantation approaches. Infection and second malignancies remain as concerns. Randomized trials are needed to compare efficacy with standard regimens.

ALG and OKT 3 seem comparable in the treatment of renal transplant rejection

ALG and OKT 3 seem comparable in the treatment of renal transplant rejection