Management hochimmunisierter Nierentransplantatempfänger

Zusammenfassung

Die Hinweise häufen sich, dass die antikörpervermittelte Abstoßung im Langzeitverlauf die Hauptursache der Nierentransplantatverluste darstellt. Die Vermeidung des antikörperbedingten Schadens beginnt bereits vor der Transplantation mit der Vermeidung von immunisierenden Ereignissen. Wenn der Patient jedoch bereits immunisiert ist, werden die präzise Charakterisierung der in seinem Blut zirkulierenden Alloantikörper und die in diesem Rahmen notwendige genaue Typisierung der HLA-Merkmale (HLA: Human Leukocyte Antigen, humanes Leukozytenantigen) des Fremdorgans unerlässlich. Um eine möglichst schnelle und erfolgreiche Transplantation hochimmunisierter Patienten zu gewährleisten, müssen mehrere Möglichkeiten wie Desensibilisierung und Anmeldung zu speziellen Allokationsprogrammen in Betracht gezogen werden. Nach der Transplantation stellen wiederum die engmaschige Überwachung der Nierenfunktion und der De-novo-Antikörperbildung sowie die Vermeidung von Unterimmunsuppression die wichtigsten Maßnahmen dar.

Schlüsselwörter

Nierentransplantation - HLA - Desensibilisierung - humorale Abstoßung - Acceptable-Mismatch-Programm

• Literatur

• 1 U.S. Department of Health & Human Services. OPTN/SRTR Annual Report 1999 – 2008. HHS/HRSA/HSB/DOT 2009
• 2 Oosterlee A, Rahmel A (Hrsg) Eurotransplant International Foundation Annual Report 2010. Leiden: Eurotransplant International Foundation; 2010
• 3 Fuggle SV, Martin S. Tools for human leukocyte antigen antibody detection and their application to transplanting sensitized patients. Transplantation 2008; 86: 384-390
• 4 Collaborative Transplant Study, University of Heidelberg. 2011 Im Internet: http://www.ctstransplant.org Stand: 1. Oktober 2012
• 5 Süsal C, Döhler B, Opelz G. Presensitized kidney graft recipients with HLA class I and II antibodies are at increased risk for graft failure: A Collaborative Transplant Study report. Hum Immunol 2009; 70: 569-573
• 6 Hidalgo LG, Campbell PM, Sis B et al. De novo donor-specific antibody at the time of kidney transplant biopsy associates with microvascular pathology and late graft failure. Am J Transplant 2009; 9: 2532-2541
• 7 Einecke G, Sis B, Reeve J et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant 2009; 9: 2520-2531
• 8 Vella JP, OʼNeill D, Atkins N et al. Sensitization to human leukocyte antigen before and after the introduction of erythropoietin. Nephrol Dial Transplant 1998; 13: 2027-2032
• 9 Meier-Kriesche HU, Scornik JC, Susskind B et al. A lifetime versus a graft life approach redefines the importance of HLA matching in kidney transplant patients. Transplantation 2009; 88: 23-29
• 10 Morales-Buenrostro LE, Terasaki PI, Marino-Vazquez LA et al. “Natural” human leukocyte antigen antibodies found in nonalloimmunized healthy males. Transplantation 2008; 86: 1111-1115
• 11 van den Berg-Loonen EM, Billen EV, Voorter CE et al. Clinical relevance of pretransplant donor-directed antibodies detected by single antigen beads in highly sensitized renal transplant patients. Transplantation 2008; 85: 1086-1090
• 12 Amico P, Honger G, Mayr M et al. Clinical relevance of pretransplant donor-specific HLA antibodies detected by single-antigen flow-beads. Transplantation 2009; 87: 1681-1688
• 13 Lefaucheur C, Loupy A, Hill GS et al. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol 2010; 21: 1398-1406
• 14 Süsal C, Ovens J, Mahmoud K et al. No association of kidney graft loss with human leukocyte antigen antibodies detected exclusively by sensitive Luminex single-antigen testing: a Collaborative Transplant Study report. Transplantation 2011; 91: 883-887
• 15 Lefaucheur C, Antoine C, Suberbielle C et al. Mastering the risk of HLA antibodies in kidney transplantation: an algorithm based on pretransplant single-antigen flow bead techniques. Am J Transplant 2011; 11: 1592-1598
• 16 Süsal C, Opelz G. Kidney graft failure and presensitization against HLA class I and class II antigens. Transplantation 2002; 73: 1269-1273
• 17 Doxiadis II, Smits JM, Persijn GG et al. It takes six to boogie: allocating cadaver kidneys in Eurotransplant. Transplantation 2004; 77: 615-617
• 18 Claas FH, Rahmel A, Doxiadis II. Enhanced kidney allocation to highly sensitized patients by the acceptable mismatch program. Transplantation 2009; 88: 447-452
• 19 Montgomery RA. Renal transplantation across HLA and ABO antibody barriers: integrating paired donation into desensitization protocols. Am J Transplant 2010; 10: 449-457
• 20 Beimler JH, Morath C, Schmidt J et al. Successful deceased-donor kidney transplantation in crossmatch-positive patients with peritransplant plasma exchange and Rituximab. Transplantation 2009; 87: 668-671
• 21 Bartel G, Wahrmann M, Regele H et al. Peritransplant immunoadsorption for positive crossmatch deceased donor kidney transplantation. Am J Transplant 2010; 10: 2033-2042
• 22 Vo AA, Lukovsky M, Toyoda M et al. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 2008; 359: 242-251
• 23 Glotz D, Antoine C, Julia P et al. Desensitization and subsequent kidney transplantation of patients using intravenous immunoglobulins (IVIg). Am J Transplant 2002; 2: 758-760
• 24 Jordan SC, Tyan D, Stablein D et al. Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial. J Am Soc Nephrol 2004; 15: 3256-3262
• 25 Morath C, Beimler J, Opelz G et al. Living donor kidney transplantation in crossmatch-positive patients enabled by peritransplant immunoadsorption and anti-CD20 therapy. Transpl Int 2012; 25: 506-517
• 26 Morath C, Zeier M, Süsal C. Desensitization of HLA-incompatible kidney recipients. N Engl J Med 2011; 365: 1644-1645
• 27 Zachary AA, Montgomery RA, Ratner LE et al. Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients. Transplantation 2003; 76: 1519-1525
• 28 Montgomery RA, Zachary AA, Racusen LC et al. Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients. Transplantation 2000; 70: 887-895
• 29 Stegall MD, Gloor J, Winters JL et al. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant 2006; 6: 346-351
• 30 Tyan DB, Li VA, Czer L et al. Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation 1994; 57: 553-562
• 31 Glotz D, Haymann JP, Sansonetti N et al. Suppression of HLA-specific alloantibodies by high-dose intravenous immunoglobulins (IVIg). A potential tool for transplantation of immunized patients. Transplantation 1993; 56: 335-337
• 32 Watanabe J, Scornik JC. IVIG and HLA antibodies. Evidence for inhibition of complement activation but not for anti-idiotypic activity. Am J Transplant 2005; 5: 2786-2790
• 33 Montgomery RA, Zachary AA. Transplanting patients with a positive donor-specific crossmatch: a single centerʼs perspective. Pediatr Transplant 2004; 8: 535-542
• 34 Montgomery RA, Lonze BE, King KE et al. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med 2011; 365: 318-326
• 35 Palmer A, Taube D, Welsh K et al. Removal of anti-HLA antibodies by extracorporeal immunoadsorption to enable renal transplantation. Lancet 1989; 1: 10-12
• 36 Higgins RM, Bevan DJ, Carey BS et al. Prevention of hyperacute rejection by removal of antibodies to HLA immediately before renal transplantation. Lancet 1996; 348: 1208-1211
• 37 Lorenz M, Regele H, Schillinger M et al. Peritransplant immunoadsorption: a strategy enabling transplantation in highly sensitized crossmatch-positive cadaveric kidney allograft recipients. Transplantation 2005; 79: 696-701
• 38 Haas M, Bohmig GA, Leko-Mohr Z et al. Peri-operative immunoadsorption in sensitized renal transplant recipients. Nephrol Dial Transplant 2002; 17: 1503-1508
• 39 Marfo K, Ling M, Bao Y et al. Lack of effect in desensitization with intravenous immunoglobulin and Rituximab in highly sensitized patients. Transplantation 2012; 94: 345-351
• 40 Gjorstrup P, Berntorp E, Larsson L et al. Kinetic aspects of the removal of IgG and inhibitors in hemophiliacs using protein A immunoadsorption. Vox Sang 1991; 61: 244-250
• 41 Belak M, Borberg H, Jimenez C et al. Technical and clinical experience with protein A immunoadsorption columns. Transfus Sci 1994; 15: 419-422
• 42 Morath C, Becker LE, Leo A et al. ABO-incompatible kidney transplantation enabled by non-antigen-specific immunoadsorption. Transplantation 2012; 93: 827-834
• 43 Goldammer A, Derfler K, Herkner K et al. Influence of plasma immunoglobulin level on antibody synthesis. Blood 2002; 100: 353-355
• 44 Biesenbach P, Schmaldienst S, Smolen JS et al. Immunoadsorption in SLE: three different high affinity columns are adequately effective in removing autoantibodies and controlling disease activity. Atheroscler Suppl 2009; 10: 114-121
• 45 Ratner LE, Rana A, Ratner ER et al. The altruistic unbalanced paired kidney exchange: proof of concept and survey of potential donor and recipient attitudes. Transplantation 2010; 89: 15-22
• 46 Tyden G, Kumlien G, Genberg H et al. ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab. Am J Transplant 2005; 5: 145-148
• 47 Thomas TC, Rollins SA, Rother RP et al. Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol 1996; 33: 1389-1401
• 48 Stegall M, Tayyab D, Lynn C et al. Terminal complement inhibition decreases early acute humoral rejection in sensitized renal transplant recipients. Am J Transplant 2010; 10: 39
• 49 Morath C, Beimler J, Opelz G et al. An integrative approach for the transplantation of high-risk sensitized patients. Transplantation 2010; 90: 645-653
• 50 Morath C, Opelz G, Zeier M et al. Prevention of antibody-mediated kidney transplant rejection. Transpl Int 2012; 25: 633-645