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      Efficacy of Anti-Interleukin-2 Receptor Antibody in Reducing the Incidence of Acute Rejection After Renal Transplantation

      letter
      1 , * , 2
      Nephro-urology monthly
      Kowsar
      Kidney transplantation, Therapeutics, Rejection

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          Abstract

          Dear Editor, Acute rejection (AR) in kidney transplant recipients is a major risk factor for chronic allograft failure and reduction in early and long term mean graft survival. New immunosuppressant agents have been developed to reduce the incidence of these episodes (1). Immunobiological drugs such as monoclonal anti-interleukin-2 receptor antibodies have shown promise in this direction; they have a more restrict immunosuppressive effect, are not related to interleukin release syndrome and are related to lower rates of CMV infection than polyclonal antibodies (2). In his trial Saghafi et al. (3) showed a reduction of Biopsy-Proven Acute Rejection (BPAR) episodes in non-related living donor kidney transplant recipients performing anti-interleukin-2 receptor, daclizumab, as an induction drug in addition to standard therapy with cyclosporine, mycophenolate and prednisone. The induction group had a statistically significant (20.8%) reduction in rejection episodes compared to control group using only standard therapy after a six month follow up (3). Resembling data had already been shown in previous studies, Vincent et al. showed similar reduction in incidence of BPAR in low immunologic risk deceased donor kidney recipients and the same rate of bacterial infections and/or viral infections, including CMV, malignances and adverse event as placebo group (4). Another study showed a reduction in the incidence of BPAR in deceased and living kidney recipients of about 14 % in the group that underwent induction therapy with daclizumab with no increase in infections and adverse events (1). Saghafi et al. in accordance with other authors showed daclizumab as an effective induction treatment option for low immunologic risk living donor kidney recipients. However, missing data about safety drug profile such as incidence of infection, adverse events, CMV infection, and early and late cyclosporine trough levels are not reported in the text. There are several studies confirming that induction therapy with either monoclonal or polyclonal antibodies in addition to standard therapy reduces the incidence of acute rejection but none of these studies have shown statistically significant improving in long term graft survival. New trials such as ELITE-symphony (5) study performing inteleukin-2 receptor antibody as a calcineurin inhibitor sparing agent showed promising results when comparing classical treatment protocol with standard cyclosporine dose, mycophenolate and corticosteroids with daclizumab, corticosteroids and mycophenolate and low dose cyclosporine or low dose tacrolimus or low dose sirolimus. This study found better outcomes in term of lower incidence of acute rejection, adverse events, infections and a better allograft survival rates in daclizumab and low dose tacrolimus group (5). Improving long-term outcomes in renal transplantation is still a field of challenge and numbness but the use of induction agents in adjunction with other drugs for reducing their side effects is a promising strategy for better graft and patient survival. Perhaps, most important induction therapy importance is in minimizing exposure to other immunosuppressive therapy and its side effects and this topic deserves research.

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          Most cited references4

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          Rabbit antithymocyte globulin versus basiliximab in renal transplantation.

          Induction therapy reduces the frequency of acute rejection and delayed graft function after transplantation. A rabbit antithymocyte polyclonal antibody or basiliximab, an interleukin-2 receptor monoclonal antibody, is most commonly used for induction. In this prospective, randomized, international study, we compared short courses of antithymocyte globulin and basiliximab in patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor. Patients taking cyclosporine, mycophenolate mofetil, and prednisone were randomly assigned to receive either rabbit antithymocyte globulin (1.5 mg per kilogram of body weight daily, 141 patients) during transplantation (day 0) and on days 1 through 4 or basiliximab (20 mg, 137 patients) on days 0 and 4. The primary end point was a composite of acute rejection, delayed graft function, graft loss, and death. At 12 months, the incidence of the composite end point was similar in the two groups (P=0.34). The antithymocyte globulin group, as compared with the basiliximab group, had lower incidences of acute rejection (15.6% vs. 25.5%, P=0.02) and of acute rejection that required treatment with antibody (1.4% vs. 8.0%, P=0.005). The antithymocyte globulin group and the basiliximab group had similar incidences of graft loss (9.2% and 10.2%, respectively), delayed graft function (40.4% and 44.5%), and death (4.3% and 4.4%). Though the incidences of all adverse events, serious adverse events, and cancers were also similar between the two groups, patients receiving antithymocyte globulin had a greater incidence of infection (85.8% vs. 75.2%, P=0.03) but a lower incidence of cytomegalovirus disease (7.8% vs. 17.5%, P=0.02). Among patients at high risk for acute rejection or delayed graft function who received a renal transplant from a deceased donor, induction therapy consisting of a 5-day course of antithymocyte globulin, as compared with basiliximab, reduced the incidence and severity of acute rejection but not the incidence of delayed graft function. Patient and graft survival were similar in the two groups. (ClinicalTrials.gov number, NCT00235300 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.
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            Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group.

            Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation. We administered daclizumab (1.0 mg per kilogram of body weight) or placebo intravenously before transplantation and once every other week afterward, for a total of five doses, to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine, azathioprine, and prednisone. The patients were followed at regular intervals for 12 months. The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation. Of the 126 patients given daclizumab, 28 (22 percent) had biopsy-confirmed episodes of acute rejection, as compared with 47 of the 134 patients (35 percent) who received placebo (P=0.03). Graft survival at 12 months was 95 percent in the daclizumab-treated patients, as compared with 90 percent in the patients given placebo (P=0.08). The patients given daclizumab did not have any adverse reactions to the drug, and at six months, there were no significant differences between the two groups with respect to infectious complications or cancers. The serum half-life of daclizumab was 20 days, and its administration resulted in prolonged saturation of interleukin-2alpha receptors on circulating lymphocytes. Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients.
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              Anti-interleukin-2 receptor antibodies—basiliximab and daclizumab—for the prevention of acute rejection in renal transplantation

              The use of antibody induction after kidney transplantation has increased from 25% to 63% in the past decade and roughly one half of the induction agent used is anti-interleukin-2 receptor antibody (IL-2RA, ie, basiliximab or daclizumab). When combined with calcineurin inhibitor (CNI)-based immunosuppression, IL-2RAs have been shown to reduce the incidence of acute rejection, one of the predictors of poor graft survival, without increasing risks of infections and malignancies in kidney transplantation. For low-immunological-risk patients, IL-2RAs, as compared with lymphocyte-depleting antibodies, are equally efficacious and have better safety profiles. For high-risk patients, however, IL-2RAs may be inferior to lymphocyte-depleting antibodies for the prophylaxis of acute rejection. In an effort to reduce toxicities of other immunosuppressive medications without increasing the risk of acute rejection and chronic graft loss, IL-2RAs have often been combined with steroid- and CNI-sparing immunosuppression protocols. More data support the benefits of early steroid withdrawal with IL-2RA in low-risk patients, but preferred induction therapy for high-risk patients has yet to be determined. Although CNI-sparing protocols with IL-2RA may preserve renal function and improve long-term survival in selected patients, further studies are needed to identify those who benefit most from this strategy.
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                Author and article information

                Journal
                Nephrourol Mon
                Nephrourol Mon
                10.5812/numonthly
                Kowsar
                Nephro-urology monthly
                Kowsar
                2251-7006
                2251-7014
                24 September 2012
                Autumn 2012
                : 4
                : 4
                : 650-651
                Affiliations
                [1 ]University of Fortaleza – UNIFOR, Fortaleza, Brazil
                [2 ]Hospital Geral de Fortaleza, Fortaleza, Brazil
                Author notes
                [* ]Corresponding author: Alexandre Braga Liborio, University of Fortaleza – UNIFOR, Fortaleza, Brazil. Tel.: +55-8599987995, E-mail: alexandreliborio@ 123456yahoo.com.br
                Article
                10.5812/numonthly.7279
                3614313
                23573511
                c383d17f-bbd4-4618-9163-4335e2a7ea01
                Copyright © 2012, Kowsar Corp.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 July 2012
                : 19 July 2012
                : 21 July 2012
                Categories
                Letter to Editor

                kidney transplantation,therapeutics,rejection
                kidney transplantation, therapeutics, rejection

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