BACKGROUND: There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy. METHODS: In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months. RESULTS: TAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6-98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up. CONCLUSIONS: In conclusion, our novel fast-track TAC-monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full-scale study will be needed to confirm our findings. TRIAL REGISTRATION: EudraCT Number: 2006-003110-18.

Berlin Brandenburg Center for Regenerative Medicine Charité University Medicine Berlin Germany

Department of Clinical and Transplant Pathology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Immunogenetics Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Nephrology and Intensive Care Medicine Charité University Medicine Berlin Germany

Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic

Institut de Transplantation Urologie Néphrologie du Centre Hospitalier Universitaire Hôtel Dieu Nantes France

Institut National de la Santé et de la Recherche Médicale INSERM U1064 France

Institute of Medical Immunology Charité University Medicine Berlin Germany

Miltenyi Biotec GmbH Bergisch Gladbach Germany

Transplant Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic

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Recent advances in kidney transplantation: a viewpoint from the Descartes advisory board