Update: Immunsuppression bei Organtransplantationen

Die Immunsuppression ist eine wesentliche Grundvoraussetzung für eine erfolgreiche Transplantation. Zur Reduktion der teils beträchtlichen Nebenwirkungen werden Kombinationstherapien mit unterschiedlichen Wirkstoffen durchgeführt. Dieser Beitrag soll einen aktuellen Überblick zur Immunsuppression nach Leber- und Nierentransplantation geben.

Abstract

Immunosuppression is an essential prerequisite for successful transplantation. In order to reduce the sometimes-considerable side effects, combination therapies with different agents are used. This article aims to provide an up-to-date overview of immunosuppression after liver and kidney transplantation.

Schlüsselwörter

Langzeitüberleben - Nebenwirkungen - Behandlungsstrategien - patientenorientiert

Key words

long-term survival - side effects - treatment strategy - patient-oriented

Publication History

Article published online:
07 September 2022

• Literatur

• 1 Houben P, Gotthardt DN, Radeleff B. et al. [Complication management after liver transplantation: Increasing patient safety by standardized approach and interdisciplinary cooperation]. Chirurg 2015; 86: 139-145
• 2 Trunecka P, Klempnauer J, Bechstein WO. et al. Renal function in De Novo liver transplant recipients receiving different prolonged-release tacrolimus regimens – The DIAMOND study. Am J Transplant 2015; 15: 1843-1854
• 3 Tremblay S, Nigro V, Weinberg J. et al. A steady-state head-tohead pharmacokinetic comparison of all FK 506 (Tacrolimus) formulations (ASTCOFF): an open-label, prospective, randomized, two-arm, three-period study. Am J Transplant 2017; 17: 432-442
• 4 Pietruck F, Abbud-Filho M, Vathsala A. et al. Conversion from MMF to enteric-coated mycophenolate sodium in stable maintenance renal transplant patients: results from three multicenter studies. Transplant Proc 2007; 39: 103-108
• 5 Winkler M, Ringe B, Schneider K. et al. Enhanced bioavailability of cyclosporine using a new oral formulation (Sandimmun optoral) in a liver-grafted patient with severe cholestasis. Transpl Int 1994; 7: 147-148
• 6 Starzl TE, Groth CG, Brettschneider L. et al. Orthotopic homotransplantation of the human liver. Ann Surg 1968; 168: 392-415
• 7 Richter S, Polychronidis G, Gotthardt DN. et al. Effect of delayed CNI-based immunosuppression with Advagraf ^® on liver function after MELD-based liver transplantation (IMUTECT). BMC Surg 2014; 14: 64
• 8 Döcke WD, Höflich C, Davis KA. et al. Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA‑DR expression: a multicenter standardized study. Clin Chem 2005; 51: 2341-2347
• 9 Cai J, Terasaki PI. Induction immunosuppression improves long-term graft and patient outcome in organ transplantation: an analysis of UNOS registry data. Transplantation 2010; 90: 1511-1515
• 10 Mangus RS, Fridell JA, Vianna RM. et al. Immunosuppression induction with rabbit anti-thymocyte globulin with or without rituximab in 1000 liver transplant patients with long-term follow-up. Liver Transpl 2012; 18: 786-795
• 11 Zhang GQ, Zhang CS, Sun N. et al. Basiliximab application on liver recipients: a meta-analysis of randomized controlled trials. Hepatobil Pancr Dis Int 2017; 16: 139-146
• 12 Turner AP, Knechtle SJ. Induction immunosuppression in liver transplantation: a review. Transpl Int 2013; 26: 673-683
• 13 Opelz G, Unterrainer C, Süsal C. et al. Efficacy and safety of antibody induction therapy in the current era of kidney transplantation. Nephrol Dial Transplant 2016; 31: 1730-1738
• 14 Adam R, Karam V, Delvart V. et al. Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry. Am J Transplant 2015; 15: 1267-1282
• 15 Kuypers DR, Peeters PC, Sennesael JJ. et al. Improved adherence to tacrolimus once-daily formulation in renal recipients: a randomized controlled trial using electronic monitoring. Transplantation 2013; 95: 333-340
• 16 McAlister VC, Haddad E, Renouf E. et al. Cyclosporin versus tacrolimus as primary immunosuppressant after liver transplantation: a meta-analysis. Am J Transplant 2006; 6: 1578-1585
• 17 Muduma G, Saunders R, Odeyemi I. et al. Systematic review and meta-analysis of Tacrolimus versus Ciclosporin as primary immunosuppression after liver transplant. PLoS One 2016; 11: e0160421
• 18 Rodriguez-Peralvarez M, Germani G, Darius T. et al. Tacrolimus trough levels, rejection and renal impairment in liver transplantation: a systematic review and meta-analysis. Am J Transplant 2012; 12: 2797-2814
• 19 Wang P, Que W, Li H. et al. Efficacy and safety of a reduced calcineurin inhibitor dose combined with mycophenolate mofetil in liver transplant patients with chronic renal dysfunction. Oncotarget 2017; 8: 57505-57515
• 20 Wiesner R, Rabkin J, Klintmalm G. et al. A randomized doubleblind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients. Liver Transpl 2001; 7: 442-450
• 21 Karie-Guigues S, Janus N, Saliba F. et al. Long-term renal function in liver transplant recipients and impact of immunosuppressive regimens (calcineurin inhibitors alone or in combination with mycophenolate mofetil): the TRY study. Liver Transpl 2009; 15: 1083-1091
• 22 Reich DJ, Clavien PA, Hodge EE. et al. MMF for renal dysfunction in liver transplant recipients on cyclosporine or tacrolimus: randomized, prospective, multicenter pilot study results. Transplantation 2005; 80: 18-25
• 23 Beckebaum S, Cicinnati VR, Radtke A. et al. Calcineurin inhibitors in liver transplantation – still champions or threatened by serious competitors?. Liver Int 2013; 33: 656-665
• 24 Saliba F, De Simone P, Nevens F. et al. Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study. Am J Transplant 2013; 13: 1734-1745
• 25 DeSimone P, Nevens F, De Carlis L. et al. Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial. Am J Transplant 2012; 12: 3008-3020
• 26 Schnitzbauer A, Sothmann J, Baier L. et al. Calcineurin inhibitor free de novo immunosuppression in liver transplant recipients with pretransplant renal impairment: results of a pilot study (PATRON07). Transplantation 2015; 99: 2565-2575
• 27 Sterneck M, Kaiser GM, Heyne N. et al. Long-term follow-up of five yr shows superior renal function with everolimus plus early calcineurin inhibitor withdrawal in the PROTECT randomized liver transplantation study. Clin Transplant 2016; 30: 741-748
• 28 Segev DL, Sozio SM, Shin EJ. et al. Steroid avoidance in liver transplantation: meta-analysis and meta-regression of randomized trials. Liver Transpl 2008; 14: 512-525
• 29 Liu YY, Li CP, Huai MS. et al. Comprehensive comparison of three different immunosuppressive regimens for liver transplant patients with hepatocellular carcinoma: steroid-free immunosuppression, induction immunosuppression and standard immunosuppression. PLoS One 2015; 10: e120939
• 30 Klintmalm GB, Davis GL, Teperman L. et al. A randomized, multicentre study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C. Liver Transpl 2011; 17: 1394-1403
• 31 Hogen R, DiNorcia J, Dhanireddy K. Antibody-mediated rejection: what is the clinical relevance?. Curr Opin Organ Transplant 2017; 22: 97-104
• 32 Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9 (Suppl. 03) S1-S155
• 33 Meier-Kriesche HU, Li S, Gruessner RWG. et al. Immunosuppression: evolution in practice and trends 1994-2004. Am J Transplant 2006; 6: 1111-1131
• 34 Ekberg H, Tedesco-Silva H, Demirbas A. et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007; 357: 2562-2575
• 35 De Fijter JW, Holdaas H, Oyen O. et al. Early conversion from calcineurin inhibitor – to everolimus-based therapy following kidney transplantation: results of the randomized ELEVATE trial. Am J Transplant 2017; 17: 1853-1867
• 36 Vincenti F, Charpentier B, Vanrenterghem Y. et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant 2010; 10: 535-546
• 37 Thomusch O, Wiesener M, Opgenoorth M. et al. Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial. Lancet 2016; 17: 3006-3016
• 38 Haller M, Royuela A, Nagler E. et al. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev 2016; (08) CD005632
• 39 Eskandary F, Bond G, Kozakowski N. et al. Diagnostic contribution of donor-specific antibody characteristics to uncover late silent antibody-mediated rejection-results of a cross-sectional screening study. Transplantation 2017; 101: 631-641
• 40 Neuberger J, Bechstein W, Kuypers D. et al. Practical Recommendations for long-term management of modifiable risks in kidney and liver transplant recipients: a guidance report by the consensus on managing modifiable risk in transplantation (COMMIT) group. Transplantation 2017; 101 (04) S1-S56
• 41 Fine RN, Becker Y, DeGeest S. et al. Nonadherence Consensus Conference Summary Report. Am J Transplant 2009; 9: 35-41
• 42 Lieber SR, Volk ML. Non-adherence and graft failure in adult liver transplant recipients. Dig Dis Sci 2013; 58: 824-834
• 43 Sellares J, de Freitas DG, Mengel M. et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 2012; 12: 388-399
• 44 Giese T, Zeier M, Schemmer P. et al. Monitoring of NFAT-regulated gene expression in the peripheral blood of allograft recipients: a novel perspective toward individually optimized drug doses of cyclosporine A. Transplantation 2004; 15: 339-344