42
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance.

          Abstract

          De novo donor-specific antibodies (dnDSA) production is a major risk factor for antibody-mediated rejection and graft loss after all solid organ transplantation. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance.

          Related collections

          Most cited references138

          • Record: found
          • Abstract: found
          • Article: not found

          A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study).

          Belatacept, a costimulation blocker, may preserve renal function and improve long-term outcomes versus calcineurin inhibitors in kidney transplantation. This Phase III study (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial) assessed a more intensive (MI) or less intensive (LI) regimen of belatacept versus cyclosporine in adults receiving a kidney transplant from living or standard criteria deceased donors. The co-primary endpoints at 12 months were patient/graft survival, a composite renal impairment endpoint (percent with a measured glomerular filtration rate (mGFR) or =10 mL/min/1.73 m(2) Month 3-Month 12) and the incidence of acute rejection. At Month 12, both belatacept regimens had similar patient/graft survival versus cyclosporine (MI: 95%, LI: 97% and cyclosporine: 93%), and were associated with superior renal function as measured by the composite renal impairment endpoint (MI: 55%; LI: 54% and cyclosporine: 78%; p < or = 0.001 MI or LI versus cyclosporine) and by the mGFR (65, 63 and 50 mL/min for MI, LI and cyclosporine; p < or = 0.001 MI or LI versus cyclosporine). Belatacept patients experienced a higher incidence (MI: 22%, LI: 17% and cyclosporine: 7%) and grade of acute rejection episodes. Safety was generally similar between groups, but posttransplant lymphoproliferative disorder was more common in the belatacept groups. Belatacept was associated with superior renal function and similar patient/graft survival versus cyclosporine at 1 year posttransplant, despite a higher rate of early acute rejection.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Banff '05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy ('CAN').

            The 8th Banff Conference on Allograft Pathology was held in Edmonton, Canada, 15-21 July 2005. Major outcomes included the elimination of the non-specific term "chronic allograft nephropathy" (CAN) from the Banff classification for kidney allograft pathology, and the recognition of the entity of chronic antibody-mediated rejection. Participation of B cells in allograft rejection and genomics markers of rejection were also major subjects addressed by the conference.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              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.
                Bookmark

                Author and article information

                Journal
                Transplantation
                Transplantation
                TP
                Transplantation
                Lippincott Williams & Wilkins
                0041-1337
                1534-6080
                January 2016
                16 December 2015
                : 100
                : 1
                : 39-53
                Affiliations
                [1] 1 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.
                [2] 2 Department of Internal Medicine, Nephrology, University of Michigan, Ann Arbor, MI.
                [3] 3 Nephrology Department and Renal Transplant Unit, Hospital del Mar, Parc de Salut Mar, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
                [4] 4 Heart and Lung Transplant Program, Department of Experimental and Specialty Medicine, Academic Hospital S. Orsola-Malpighi, University of Bologna, Bologna, Italy.
                [5] 5 Pathology Department, University of Pittsburgh Medical Center, Pittsburgh, PA.
                [6] 6 Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI.
                [7] 7 Transplantation Immunology, Department of Transfusion Medicine, Padua University Hospital, Padua, Italy.
                Author notes
                Correspondence: Jacqueline G. O'Leary MD, MPH, Baylor University Medical Center, 3410 Worth St. Ste. 860, Dallas, TX 75246. ( jacquelo@ 123456baylorhealth.edu ).
                Article
                TP500141 00012
                10.1097/TP.0000000000000869
                4683034
                26680372
                34d2692c-de28-44e9-a69a-3e0f85b3dd0a
                Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

                History
                : 18 February 2015
                : 25 May 2015
                : 7 June 2015
                Categories
                Reviews
                Custom metadata
                TRUE

                Comments

                Comment on this article