Wann sollte man die Immunsuppression nach Ende der Nierentransplantatfunktion absetzen?

Zusammenfassung

In den nächsten Jahren wird bei vielen Patienten über eine zweite, dritte oder auch vierte Nierentransplantation nachgedacht werden, da die initialen Transplantate nach längerer oder kürzerer Funktion nicht mehr ausreichend entgiften und damit erneut eine maschinelle Nierenersatztherapie notwendig ist. Auch wenn das transplantierte Organ nicht mehr ausreichend funktionstüchtig ist, bleibt es ein Fremdkörper, kann weiterhin vom Körper als ‚fremd‘ erkannt und damit auch abgestoßen werden. Dies wiederum kann massive Komplikationen für betroffene Patienten nach sich ziehen. Auf der anderen Seite ist eine Immunsuppression durchaus mit kardiovaskulären, infektiologischen, aber auch mit malignen Risiken für den Patienten unter einer maschinellen Nierenersatztherapie verbunden. Damit stellt sich dem behandelnden Arzt bei einem versagenden Transplantat immer die Frage, wie mittelfristig mit der verwendeten immunsuppressiven Behandlung umgegangen werden sollte.

• Literatur

• 1 Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant 2011; 11: 450-462 doi: 10.1111/j.1600–6143.2010.03283.x
• 2 Cecka JM. The UNOS Renal Transplant Registry. Clin Transpl 2002; 1-20
• 3 Knoll G, Muirhead N, Trpeski L. et al. Patient survival following renal transplant failure in Canada. Am J Transplant 2005; 5: 1719-1724 doi: 10.1111/j.1600–6143.2005.00921.x
• 4 Gill JS, Abichandani R, Kausz AT. et al. Mortality after kidney transplant failure: the impact of non-immunologic factors. Kidney Int 2002; 62: 1875-1883 doi: 10.1046/j.1523–1755.2002.00640.x
• 5 Rao PS, Schaubel DE, Jia X. et al. Survival on dialysis post-kidney transplant failure: results from the Scientific Registry of Transplant Recipients. Am J Kidney Dis 2007; 49: 294-300 doi: 10.1053/j.ajkd.2006.11.022
• 6 Gill JS, Rose C, Pereira BJ. et al. The importance of transitions between dialysis and transplantation in the care of end-stage renal disease patients. Kidney Int 2007; 71: 442-447 doi: 10.1038/sj.ki.5002072
• 7 Meier-Kriesche HU, Kaplan B. Death after graft loss: a novel endpoint for renal transplantation. Transplant Proc 2001; 33: 3405-3406
• 8 McCaughan JA, Patterson CC, Maxwell AP. et al. Factors influencing survival after kidney transplant failure. Transplant Res 2014; 3: 18 doi: 10.1186/2047–1440–3-18
• 9 Pham PT, Pham PC. Immunosuppressive management of dialysis patients with recently failed transplants. Semin Dial 2011; 24: 307-313 doi: 10.1111/j.1525–139X.2011.00864.x
• 10 Bayliss GP, Gohh RY, Morrissey PE. et al. Immunosuppression after renal allograft failure: a survey of US practices. Clin Transplant 2013; 27: 895-900 doi: 10.1111/ctr.12254
• 11 Kassakian CT, Ajmal S, Gohh RY. et al. Immunosuppression in the failing and failed transplant kidney: optimizing outcomes. Nephrol Dial Transplant 2016; 31: 1261-1269 doi: 10.1093/ndt/gfv256
• 12 Casey MJ, Wen X, Kayler LK. et al. Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure. Transplantation 2014; 98: 306-311 doi: 10.1097/TP.0000000000000057
• 13 Jassal SV, Lok CE, Walele A. et al. Continued transplant immunosuppression may prolong survival after return to peritoneal dialysis: results of a decision analysis. Am J Kidney Dis 2002; 40: 178-183 doi: 10.1053/ajkd.2002.33927
• 14 Smak Gregoor PJ, Zietse R, van Saase JL. et al. Immunosuppression should be stopped in patients with renal allograft failure. Clin Transplant 2001; 15: 397-401
• 15 Woodside KJ, Schirm ZW, Noon KA. et al. Fever, infection, and rejection after kidney transplant failure. Transplantation 2014; 97: 648-653 doi: 10.1097/01.TP.0000437558
• 16 Gregoor PJ, Kramer P, Weimar W van Saase JL. Infections after renal allograft failure in patients with or without low-dose maintenance immunosuppression. Transplantation 1997; 63: 1528-1530
• 17 Perl J, Zhang J, Gillespie B. et al. Reduced survival and quality of life following return to dialysis after transplant failure: the Dialysis Outcomes and Practice Patterns Study. Nephrol Dial Transplant 2012; 27: 4464-4472 doi: 10.1093/ndt/gfs386
• 18 Vajdic CM, van Leeuwen MT, Webster AC. et al. Cutaneous melanoma is related to immune suppression in kidney transplant recipients. Cancer Epidemiol Biomarkers Prev 2009; 18: 2297-2303 doi: 10.1158/1055–9965.EPI-09–0278
• 19 Stewart JH, Vajdic CM, van Leeuwen MT. et al. The pattern of excess cancer in dialysis and transplantation. Nephrol Dial Transplant 2009; 24: 3225-3231 doi: 10.1093/ndt/gfp331
• 20 Dantal J, Hourmant M, Cantarovich D. et al. Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens. Lancet 1998; 351: 623-628 doi: 10.1016/S0140–6736(97)08496–1
• 21 Gallagher MP, Kelly PJ, Jardine M. et al. Long-term cancer risk of immunosuppressive regimens after kidney transplantation. J Am Soc Nephrol 2010; 21: 852-858 doi: 10.1681/ASN.2009101043
• 22 van Leeuwen MT, Webster AC, McCredie MR. et al. Effect of reduced immunosuppression after kidney transplant failure on risk of cancer: population based retrospective cohort study. BMJ 2010; 340: c570 doi: 10.1136/bmj.c570
• 23 Bamgbola O. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Ther Adv Endocrinol Metab 2016; 7: 110-127 doi: 10.1177/2042018816641580
• 24 Zsom L, Wagner L, Fulop T. Minimization vs tailoring: where do we stand with personalized immunosuppression during renal transplantation in 2015?. World J Transplant 2015; 5: 73-80 doi: 10.5500/wjt.v5.i3.73
• 25 Noel C, Hazzan M, Boukelmoune M. et al. Indication for allograft nephrectomy after irreversible rejection: is there an ideal delay?. Transplant Proc 1997; 29: 145-146 doi: 10.1016/S0041–1345(96)00041–3
• 26 Freier DT, Haines RF, Rosenzweig J. et al. Sequential renal transplants: some surgical and immunological implications on management of the first homograft. Surgery 1976; 79: 262-267
• 27 DiSesa VJ, Tilney NL. Conservative management of the failed renal allograft: indications for transplant nephrectomy. Curr Surg 1982; 39: 417-418
• 28 Thomas PP, Jacob CK, Kirubakaran MG. et al. Indication for routine allograft nephrectomy in cases of irreversible rejection. Transplantation 1989; 48: 155
• 29 Matzinger P. Graft tolerance: a duel of two signals. Nat Med 1999; 5: 616-617 doi: 10.1038/9458
• 30 Askandarani S, Aloudah N, Al Enazi H. et al. Late renal allograft rupture associated with cessation of immunosuppression following graft failure. Case Rep Transplant 2011; 2011: 512893 doi: 10.1155/2011/512893
• 31 Vanrenterghem Y, Khamis S. The management of the failed renal allograft. Nephrol Dial Transplant 1996; 11: 955-957 doi: 10.1093/ndt/11.6.955
• 32 Roberts CS, LaFond J, Fitts CT. et al. New patterns of transplant nephrectomy in the cyclosporine era. J Am Coll Surg 1994; 178: 59-64
• 33 O’Sullivan DC, Murphy DM, McLean P. et al. Transplant nephrectomy over 20 years: factors involved in associated morbidity and mortality. J Urol 1994; 151: 855-858 doi: 10.1016/S0022–5347(17)35105–4
• 34 Johnston O, Rose C, Landsberg D. et al. Nephrectomy after transplant failure: current practice and outcomes. Am J Transplant 2007; 7: 1961-1967 doi: 10.1111/j.1600–6143.2007.01884.x
• 35 Lopez-Gomez JM, Perez-Flores I, Jofre R. et al. Presence of a failed kidney transplant in patients who are on hemodialysis is associated with chronic inflammatory state and erythropoietin resistance. J Am Soc Nephrol 2004; 15: 2494-2501 doi. 10.1097/01.ASN.0000137879.97445.6E
• 36 Ayus JC, Achinger SG. At the peril of dialysis patients: ignoring the failed transplant. Semin Dial 2005; 18: 180-184 doi: 10.1111/j.1525–139X.2005.18304.x
• 37 Ayus JC, Achinger SG, Lee S. et al. Transplant nephrectomy improves survival following a failed renal allograft. J Am Soc Nephrol 2010; 21: 374-380 doi: 10.1681/ASN.2009050480
• 38 Rodger RS, Watson MJ, Sellars L. et al. Hypothalamic-pituitary-adrenocortical suppression and recovery in renal transplant patients returning to maintenance dialysis. Q J Med 1986; 61: 1039-1046 doi: 10.1093/oxfordjournals.qjmed.a068059
• 39 Verresen L, Vanrenterghem Y, Waer M. et al. Corticosteroid withdrawal syndrome in dialysis patients. Nephrol Dial Transplant 1988; 3: 476-477 doi: 10.1093/oxfordjournals.ndt.a091703
• 40 Shapiro R, Carroll PB, Tzakis AG. et al. Adrenal reserve in renal transplant recipients with cyclosporine, azathioprine, and prednisone immunosuppression. Transplantation 1990; 49: 1011-1013
• 41 Bargman JM, Thorpe KE, Churchill DN. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol 2001; 12: 2158-2162
• 42 Shemin D, Bostom AG, Laliberty P. et al. Residual renal function and mortality risk in hemodialysis patients. Am J Kidney Dis 2001; 38: 85-90 doi: 10.1053/ajkd.2001.25198
• 43 Lameire NH. The impact of residual renal function on the adequacy of peritoneal dialysis. Nephron 1997; 77: 13-28 doi: 10.1159/000190242
• 44 Perl J, Dong J, Rose C. et al. Is dialysis modality a factor in the survival of patients initiating dialysis after kidney transplant failure?. Perit Dial Int 2013; 33: 618-628 doi: 10.3747/pdi.2012.00280
• 45 Wang AY, Lai KN. The importance of residual renal function in dialysis patients. Kidney Int 2006; 69: 1726-1732 doi: 10.1038/sj.ki.5000382
• 46 Pham PT, Everly M, Faravardeh A. et al. Management of patients with a failed kidney transplant: Dialysis reinitiation, immunosuppression weaning, and transplantectomy. World J Nephrol 2015; 4: 148-159 doi: 10.5527/wjn.v4.i2.148; doi: 10.5527/wjn.v4.i2.148
• 47 Wong G, Chua S, Chadban SJ. et al. Waiting time between failure of first graft and second kidney transplant and graft and patient survival. Transplantation 2016; 100: 1767-1775 doi: 10.1097/TP.0000000000000953
• 48 Augustine JJ, Woodside KJ, Padiyar A. et al. Independent of nephrectomy, weaning immunosuppression leads to late sensitization after kidney transplant failure. Transplantation 2012; 94: 738-743 doi: 10.1097/TP.0b013e3182612921
• 49 Singh P, Filippone EJ, Colombe BW. et al. Sensitization trends after renal allograft failure: the role of DQ eplet mismatches in becoming highly sensitized. Clin Transplant 2016; 30: 71-80 doi: 10.1111/ctr.12663
• 50 Rao SBR PS, Pastan S, Gebel H. et al. Gradual vs rapid withdrawal of immunosuppression after kidney allograft failure results in less allosensitization, decreased rate of de-novo donor specific antibody and reduced need for allograft nephrectomy. Am J Transplant 2013; 13 [abstract]
• 51 Sumrani N, Delaney V, Hong JH. et al. The influence of nephrectomy of the primary allograft on retransplant graft outcome in the cyclosporine era. Transplantation 1992; 53: 52-55
• 52 Khakhar AK, Shahinian VB, House AA. et al. The impact of allograft nephrectomy on percent panel reactive antibody and clinical outcome. Transplant Proc 2003; 35: 862-863 doi: 10.1016/S0041–1345(02)04031–9
• 53 Douzdjian V, Rice JC, Carson RW. et al. Renal retransplants: effect of primary allograft nephrectomy on early function, acute rejection and outcome. Clin Transplant 1996; 10: 203-208
• 54 Del Bello A, Congy-Jolivet N, Sallusto F. et al. Donor-specific antibodies after ceasing immunosuppressive therapy, with or without an allograft nephrectomy. Clin J Am Soc Nephrol 2012; 7: 1310-1319 doi: 10.2215/CJN.00260112
• 55 Ramsdell F, Fowlkes BJ. Maintenance of in vivo tolerance by persistence of antigen. Science 1992; 257: 1130-1134 doi: 10.2215/CJN.00260112
• 56 Nishinaka H, Nakafusa Y, Hirano T. et al. Graft persistence effectively induces and maintains donor-specific unresponsiveness. J Surg Research 1997; 68: 145-152 doi: 10.1006/jsre.1997.5053
• 57 Jackson A, McSherry C, Butters K. et al. Pretransplant exposure to donor HLA-DR antigen in random transfusion units and the development of donor antigen-specific hyporeactivity. Hum Immunol 1997; 55: 148-153 doi: 10.1016/S0198–8859(97)0098–0
• 58 Scornik JC, Kriesche HU. Human leukocyte antigen sensitization after transplant loss: timing of antibody detection and implications for prevention. Hum Immunol 2011; 72: 398-401 doi: 10.1016/j.humimm.2011.02.018
• 59 Del Bello A, Congy N, Sallusto F. et al. Anti-human leukocyte antigen immunization after early allograft nephrectomy. Transplantation 2012; 93: 936-941 doi: 10.1097/TP.0b013e31824b3720
• 60 Kendrick EA, Davis CL. Managing the failing allograft. Semin Dial 2005; 18: 529-539 doi: 10.1111/j.1525–139X.2005.00100.x
• 61 Bennett WM. The failed renal transplant: in or out?. Semin Dial 2005; 188-189 doi: 10.1111/j.1525–139X.2005.00100.x
• 62 Andrews PA. Summary of the British Transplantation Society Guidelines for management of the failing kidney transplant. Transplantation 2014; 98: 1130-1133 doi: 10.1097/TP.0000000000000426