Dialyse aktuell 2020; 24(08): 309-318
DOI: 10.1055/a-1176-6416
Schwerpunkt
Transplantation
© Georg Thieme Verlag Stuttgart · New York

Infektionen unter Immunsuppression nach Nierentransplantation

Eine aktuelle Übersicht
Stephan Kemmner
1   Transplantationszentrum, Klinikum der Universität München, LMU München
,
Ulf Schönermarck
2   Nephrologisches Zentrum, Medizinische Klinik IV, Klinikum der Universität München, LMU München
› Author Affiliations
Further Information

Publication History

Publication Date:
12 October 2020 (online)

ZUSAMMENFASSUNG

Unter immunsuppressiver Therapie besteht ein deutlich erhöhtes Infektionsrisiko nach Nierentransplantation (NTx), insbesondere für virale Infektionen. Bereits vor einer geplanten NTx sollte auf einen aktuellen Impfstatus geachtet werden, da nach einer Transplantation unter immunsuppressiver Therapie einerseits Lebendimpfstoffe nicht mehr gegeben werden dürfen und andererseits eine adäquate Impfantwort schwieriger zu erreichen ist. Die saisonale Influenzaimpfung kann bereits einen Monat nach Transplantation gegeben werden, für alle anderen Impfungen wird ein Abwarten von 3–6 Monaten empfohlen. Eine prophylaktische Therapie kann das Auftreten bestimmter Infektionen effektiv verhindern. Nach NTx sollte für die ersten 6 Monate eine PjP-Prophylaxe (PjP: Pneumocystis-jirovecii-Pneumonie) mit Trimethoprim/Sulfamethoxazol verabreicht werden. Eine CMV-Prophylaxe (CMV: Zytomegalievirus) mit Valganciclovir erfolgt in Abhängigkeit vom Sero-Status von Empfänger und Spender i. d. R. für 3 bzw. 6 Monate. Im Falle einer Infektion kann in Abhängigkeit vom Schweregrad der Antimetabolit (meist MMF: Mycophenolatmofetil) dosishalbiert oder pausiert werden, jedoch ist dies mit einem erhöhten Rejektionsrisiko verbunden. Insbesondere bei Infektionen mit CMV und BKV (Polyomavirus BK) kann anstelle von MMF ein mTOR-Inhibitor (mTOR: „mechanistic target of rapamycin“) eingesetzt werden in Kombination mit einem niedrigdosierten Calcineurininhibitor (CNI). Bei einer COVID-19-Erkrankung (COVID-19: Coronavirus Disease 2019) nach NTx sollte wie bei anderen Infektionen in einer Kombinationstherapie zunächst der Antimetabolit bzw. der mTOR-Inhibitor dosisreduziert oder pausiert werden. Ein Absetzen des CNIs bei COVID-19 erscheint aus unserer Sicht nicht regelhaft indiziert, sondern bleibt schweren Verläufen im Einzelfall vorbehalten. Im Falle einer antiviralen Therapie bei COVID-19 muss immer an mögliche Interaktionen mit den Immunsuppressiva (v. a. mit CNI und mTOR-Inhibitoren) gedacht werden.

 
  • Literatur

  • 1 Coemans M, Susal C, Dohler B. et al Analyses of the short- and long-term graft survival after kidney transplantation in Europe between 1986 and 2015. Kidney Int 2018; 94: 964-973 doi:10.1016/j.kint.2018.05.018
  • 2 Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004; 351: 2715-2729 doi:10.1056/NEJMra033540
  • 3 Opelz G, Döhler B. Association of HLA mismatch with death with a functioning graft after kidney transplantation: a collaborative transplant study report. Am J Transplant 2012; 12: 3031-3038 doi:10.1111/j.1600-6143.2012.04226.x
  • 4 Vogelzang JL, van Stralen KJ, Noordzij M. et al Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry. Nephrol Dial Transplant 2015; 30: 1028-1037 doi:10.1093/ndt/gfv007
  • 5 Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357: 2601-2614 doi:10.1056/NEJMra064928
  • 6 Sawyer RG, Crabtree TD, Gleason TG. et al Impact of solid organ transplantation and immunosuppression on fever, leukocytosis, and physiologic response during bacterial and fungal infections. Clin Transplant 1999; 13: 260-265 doi:10.1034/j.1399-0012.1999.130307.x
  • 7 Huang C, Wang Y, Li X. et al Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506 doi:10.1016/S0140-6736(20)30183-5
  • 8 Hanaway MJ, Woodle ES, Mulgaonkar S. et al Alemtuzumab induction in renal transplantation. N Engl J Med 2011; 364: 1909-1919 doi:10.1056/NEJMoa1009546
  • 9 Luan FL, Samaniego M, Kommareddi M. et al Choice of induction regimens on the risk of cytomegalovirus infection in donor-positive and recipient-negative kidney transplant recipients. Transpl Infect Dis 2010; 12: 473-479 doi:10.1111/j.1399-3062.2010.00532.x
  • 10 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 doi:10.1056/NEJMoa067411
  • 11 Webster AC, Woodroffe RC, Taylor RS. et al Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data. BMJ 2005; 331: 810 doi:10.1136/bmj.38569.471007.AE
  • 12 Webster A, Woodroffe RC, Taylor RS. et al Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev 2005: CD003961 doi:10.1002/14651858.CD003961.pub2
  • 13 Opelz G, Döhler B. Association between steroid dosage and death with a functioning graft after kidney transplantation. Am J Transplant 2013; 13: 2096-2105 doi:10.1111/ajt.12313
  • 14 Rizzari MD, Suszynski TM, Gillingham KJ. et al Ten-year outcome after rapid discontinuation of prednisone in adult primary kidney transplantation. Clin J Am Soc Nephrol 2012; 7: 494-503 doi:10.2215/CJN.08630811
  • 15 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; 388: 3006-3016 doi:10.1016/S0140-6736(16)32187-0
  • 16 Matas AJ, Smith JM, Skeans MA. et al OPTN/SRTR 2013 Annual Data Report: kidney. Am J Transplant 2015; 15 (Suppl. 02) 1-34 doi:10.1111/ajt.13195
  • 17 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 doi:10.1111/j.1600-6143.2009.03005.x
  • 18 Sommerer C, Duerr M, Witzke O. et al Five-year outcomes in kidney transplant patients randomized to everolimus with cyclosporine withdrawal or low-exposure cyclosporine versus standard therapy. Am J Transplant 2018; 18: 2965-2976 doi:10.1111/ajt.14897
  • 19 Pascual J, Berger SP, Witzke O. et al Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation. J Am Soc Nephrol 2018; 29: 1979-1991 doi:10.1681/ASN.2018010009
  • 20 Brennan DC. Introduction: Kidney Transplantation and Viral Infection. Semin Nephrol 2016; 36: 343 doi:10.1016/j.semnephrol.2016.05.010
  • 21 Kamar N, Bendall R, Legrand-Abravanel F. et al Hepatitis E. Lancet 2012; 379: 2477-2488 doi:10.1016/S0140-6736(11)61849-7
  • 22 Pischke S, Behrendt P, Bock CT. et al Hepatitis E in Germany – an under-reported infectious disease. Dtsch Arztebl Int 2014; 111: 577-583 doi:10.3238/arztebl.2014.0577
  • 23 Kamar N, Rostaing L, Legrand-Abravanel F. et al How should hepatitis E virus infection be defined in organ-transplant recipients?. Am J Transplant 2013; 13: 1935-1936 doi:10.1111/ajt.12253
  • 24 Kamar N, Selves J, Mansuy JM. et al Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 2008; 358: 811-817 doi:10.1056/NEJMoa0706992
  • 25 Suneetha PV, Pischke S, Schlaphoff V. et al Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection. Hepatology 2012; 55: 695-708 doi:10.1002/hep.24738
  • 26 Kamar N, Garrouste C, Haagsma EB. et al Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 2011; 140: 1481-1489 doi:10.1053/j.gastro.2011.02.050
  • 27 Danziger-Isakov L, Kumar D. Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant 2019; 33: e13563 doi:10.1111/ctr.13563
  • 28 Pérez-Romero P, Bulnes-Ramos A, Torre-Cisneros J. et al Influenza vaccination during the first 6 months after solid organ transplantation is efficacious and safe. Clin Microbiol Infect 2015; 21: 1040.e1011-8 doi:10.1016/j.cmi.2015.07.014
  • 29 Natori Y, Shiotsuka M, Slomovic J. et al A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients. Clin Infect Dis 2018; 66: 1698-1704 doi:10.1093/cid/cix1082
  • 30 Gangappa S, Wrammert J, Wang D. et al Kinetics of antibody response to influenza vaccination in renal transplant recipients. Transpl Immunol 2019; 53: 51-60 doi:10.1016/j.trim.2019.01.001
  • 31 Kumar D, Ferreira VH, Blumberg E. et al A 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant Recipients. Clin Infect Dis 2018; 67: 1322-1329 doi:10.1093/cid/ciy294
  • 32 Dos Santos G, Seifert HA, Bauchau V. et al Adjuvanted (AS03) A/H1N1 2009 Pandemic Influenza Vaccines and Solid Organ Transplant Rejection: Systematic Signal Evaluation and Lessons Learnt. Drug Saf 2017; 40: 693-702 doi:10.1007/s40264-017-0532-3
  • 33 Cohet C, Haguinet F, Dos Santos G. et al Effect of the adjuvanted (AS03) A/H1N1 2009 pandemic influenza vaccine on the risk of rejection in solid organ transplant recipients in England: a self-controlled case series. BMJ Open 2016; 6: e009264 doi:10.1136/bmjopen-2015-009264
  • 34 Hurst FP, Lee JJ, Jindal RM. et al Outcomes associated with influenza vaccination in the first year after kidney transplantation. Clin J Am Soc Nephrol 2011; 6: 1192-1197 doi:10.2215/CJN.05430610
  • 35 Miller G, Schaefer H, Yoder S. et al A randomized, placebo-controlled phase I trial of live, attenuated herpes zoster vaccine in subjects with end-stage renal disease immunized prior to renal transplantation. Transpl Infect Dis 2018; 20: e12874 doi:10.1111/tid.12874
  • 36 Virusinfektionen bei Organ- und allogen Stammzell-Transplantierten: Diagnostik, Prävention und Therapie. AWMF online 2019. Im Internet https://www.awmf.org/uploads/tx_szleitlinien/093-002l_S2k_Virusinfektionen-Organtransplantierte-alloge-Stammzell-Transplantierten-Diagnostik-Praevention-Therapie__2019-06.pdf Stand: 08.09.2020
  • 37 Vink P, Ramon Torrell JM, Sanchez Fructuoso A. et al Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clin Infect Dis 2020; 70: 181-190 doi:10.1093/cid/ciz177
  • 38 Kotton CN, Kumar D, Caliendo AM. et al The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation 2018; 102: 900-931 doi:10.1097/TP.0000000000002191
  • 39 Harvala H, Stewart C, Muller K. et al High risk of cytomegalovirus infection following solid organ transplantation despite prophylactic therapy. J Med Virol 2013; 85: 893-898 doi:10.1002/jmv.23539
  • 40 Manuel O, Kralidis G, Mueller NJ. et al Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2013; 13: 2402-2410 doi:10.1111/ajt.12388
  • 41 Myhre HA, Haug Dorenberg D, Kristiansen KI. et al Incidence and outcomes of ganciclovir-resistant cytomegalovirus infections in 1244 kidney transplant recipients. Transplantation 2011; 92: 217-223 doi:10.1097/TP.0b013e31821fad25
  • 42 Iriart X, Challan Belval T, Fillaux J. et al Risk factors of Pneumocystis pneumonia in solid organ recipients in the era of the common use of posttransplantation prophylaxis. Am J Transplant 2015; 15: 190-199 doi:10.1111/ajt.12947
  • 43 Martin SI, Fishman JA. Pneumocystis pneumonia in solid organ transplantation. Am J Transplant 2013; 13 (Suppl. 04) 272-279 doi:10.1111/ajt.12119
  • 44 Lufft V, Kliem V, Behrend M. et al Incidence of Pneumocystis carinii pneumonia after renal transplantation. Impact of immunosuppression. Transplantation 1996; 62: 421-423 doi:10.1097/00007890-199608150-00022
  • 45 Natori Y, Ferreira VH, Nellimarla S. et al Incidence, Outcomes, and Long-term Immune Response to Tuberculosis in Organ Transplant Recipients. Transplantation 2019; 103: 210-215 doi:10.1097/TP.0000000000002340
  • 46 Wolf S, Lauseker M, Schiergens T. et al Infections after kidney transplantation: A comparison of mTOR-Is and CNIs as basic immunosuppressants. A systematic review and meta-analysis. Transpl Infect Dis 2020: e13267 doi:10.1111/tid.13267
  • 47 Tedesco-Silva H, Felipe C, Ferreira A. et al Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses. Am J Transplant 2015; 15: 2655-2664 doi:10.1111/ajt.13327
  • 48 Radtke J, Dietze N, Spetzler VN. et al Fewer cytomegalovirus complications after kidney transplantation by de novo use of mTOR inhibitors in comparison to mycophenolic acid. Transpl Infect Dis 2016; 18: 79-88 doi:10.1111/tid.12494
  • 49 Zhou F, Yu T, Du R. et al Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395: 1054-1062 doi:10.1016/S0140-6736(20)30566-3
  • 50 Zhu L, Xu X, Ma K. et al Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. Am J Transplant 2020; 20: 1859-1863 doi:10.1111/ajt.15869
  • 51 Guillen E, Pineiro GJ, Revuelta I. et al Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?. Am J Transplant 2020; 20: 1875-1878 doi:10.1111/ajt.15874
  • 52 Akalin E, Azzi Y, Bartash R. et al Covid-19 and Kidney Transplantation. N Engl J Med 2020; 382: 2475-2477 doi:10.1056/NEJMc2011117
  • 53 Alberici F, Delbarba E, Manenti C. et al A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney Int 2020; 97: 1083-1088 doi:10.1016/j.kint.2020.04.002
  • 54 Banerjee D, Popoola J, Shah S. et al COVID-19 infection in kidney transplant recipients. Kidney Int 2020; 97: 1076-1082 doi:10.1016/j.kint.2020.03.018
  • 55 Nair V, Jandovitz N, Hirsch JS. et al COVID-19 in kidney transplant recipients. Am J Transplant 2020; 20: 1819-1825 doi:10.1111/ajt.15967
  • 56 Montagud-Marrahi E, Cofan F, Torregrosa JV. et al Preliminary data on outcomes of SARS-CoV-2 infection in a Spanish single center cohort of kidney recipients. Am J Transplant 2020 May 5; 10.1111/ajt.15970. doi:10.1111/ajt.15970. Online ahead of print
  • 57 Columbia University Kidney Transplant Program. Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New York. J Am Soc Nephrol 2020; 31: 1150-1156 doi:10.1681/ASN.2020030375
  • 58 Zhu L, Gong N, Liu B. et al Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China. Eur Urol 2020; 77: 748-754 doi:10.1016/j.eururo.2020.03.039
  • 59 Baud D, Qi X, Nielsen-Saines K. et al Real estimates of mortality following COVID-19 infection. Lancet Infect Dis 2020; 20: 773 doi:10.1016/S1473-3099(20)30195-X
  • 60 Maggiore U, Abramowicz D, Crespo M. et al How should I manage immunosuppression in a kidney transplant patient with COVID-19? An ERA-EDTA DESCARTES expert opinion. Nephrol Dial Transplant 2020; 35: 899-904 doi:10.1093/ndt/gfaa130
  • 61 Mehta P, McAuley DF, Brown M. et al COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395: 1033-1034 doi:10.1016/S0140-6736(20)30628-0
  • 62 Bussalino E, De Maria A, Russo R. et al Immunosuppressive therapy maintenance in a kidney transplant recipient with SARS-CoV-2 pneumonia: A case report. Am J Transplant 2020; 20: 1922-1924 doi:10.1111/ajt.15920
  • 63 Romanelli A, Mascolo S. Immunosuppression drug-related and clinical manifestation of Coronavirus disease 2019: A therapeutical hypothesis. Am J Transplant 2020; 20: 1947-1948 doi:10.1111/ajt.15905
  • 64 Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395: 473-475 doi:10.1016/S0140-6736(20)30317-2
  • 65 Meziyerh S, Zwart TC, van Etten RW. et al Severe COVID-19 in a renal transplant recipient: A focus on pharmacokinetics. Am J Transplant 2020; 20: 1896-1901 doi:10.1111/ajt.15943
  • 66 Bartiromo M, Borchi B, Botta A. et al Threatening drug-drug interaction in a kidney transplant patient with Coronavirus Disease 2019 (COVID-19). Transpl Infect Dis 2020; 22: e13286 doi:10.1111/tid.13286
  • 67 Xia T, Wang Y. Coronavirus disease 2019 and transplantation: The combination of lopinavir/ritonavir and hydroxychloroquine is responsible for excessive tacrolimus trough level and unfavorable outcome. Am J Transplant 2020; 20: 2630-2631 doi:10.1111/ajt.15992
  • 68 Cao B, Wang Y, Wen D. et al A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med 2020; 382: 1787-1799 doi:10.1056/NEJMoa2001282
  • 69 Mehra MR, Desai SS, Ruschitzka F. et al Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet 2020 May 22; S0140-6736(20)31180–6. doi:10.1016/S0140-6736(20)31180-6. Online ahead of print
  • 70 Lauterio A, Valsecchi M, Santambrogio S. et al Successful recovery from severe COVID-19 pneumonia after kidney transplantation: the interplay between immunosuppression and novel therapy including tocilizumab. Transpl Infect Dis 2020 May 25 e13334 doi:10.1111/tid.13334. Online ahead of print
  • 71 Willicombe M, Thomas D, McAdoo S. COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?. J Am Soc Nephrol 2020; 31: 1145-1146 doi:10.1681/ASN.2020030348
  • 72 Coates PT, Wong G, Drueke T. et al Early experience with COVID-19 in kidney transplantation. Kidney Int 2020; 97: 1074-1075 doi:10.1016/j.kint.2020.04.001
  • 73 Kronbichler A, Gauckler P, Windpessl M. et al COVID-19: implications for immunosuppression in kidney disease and transplantation. Nat Rev Nephrol 2020; 16: 365-367 doi:10.1038/s41581-020-0305-6
  • 74 de Wilde AH, Zevenhoven-Dobbe JC, van der Meer Y. et al Cyclosporin A inhibits the replication of diverse coronaviruses. J Gen Virol 2011; 92: 2542-2548 doi:10.1099/vir.0.034983-0.
  • 75 Kemmner S, Guba MO, Schonermarck U. et al Cyclosporine as a preferred calcineurin inhibitor in renal allograft recipients with COVID-19 infection. Kidney Int 2020; 98: 507-508 doi:10.1016/j.kint.2020.05.024
  • 76 Rodriguez-Cubillo B, de la Higuera MAM, Lucena R. et al Should cyclosporine be useful in renal transplant recipients affected by SARS-CoV-2?. Am J Transplant 2020 Jun 12; 10.1111/ajt.16141. doi:10.1111/ajt.16141. Online ahead of print
  • 77 Marx D, Moulin B, Fafi-Kremer S. et al First case of COVID-19 in a kidney transplant recipient treated with belatacept. Am J Transplant 2020; 20: 1944-1946 doi:10.1111/ajt.15919