INDUCTION IMMUNOSUPPRESSION

O. Viklicky¹, J. Slatinska¹, H. Volk², B. Sawitzki³, M. Burgelova¹, P. Reinke^4
1Department Of Nephrology, IKEM, Prague 4/CZECH REPUBLIC, ², Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin/GERMANY, ³, Institute for Medical Immunology, Berlin/GERMANY, ⁴Department Of Nephrology And Intensive Care Ccv, Charité-Universitätsmedizin Berlin, Berlin/GERMANY

Body: Introduction: Novel induction protocols with campath 1H allow long-term immunosupression based on a single agent but frequent rejections were observed mainly due to recently activated memory T cells. The aim of this study was to prove the efficacy of combined induction agents, campath 1H and infliximab, in kidney transplant recipients with frequently monitored biomarkers of rejection and tolerance. Methods: The study was single centre prospective randomized phase 2 clinical trial within RISET consortium. 20 primary kidney transplant recipients with low immunological risk (PRA< 10%) received kidney grafts from deceased donors and received campath 1H 20mg i.v. prior reperfusion and at day 1 followed by infliximab 5mg/kg i.v. at day 2. For first 14 days all patients received tacrolimus and at 14 day they were randomized to continue with either tacrolimus or sirolimus monotherapy. Tolerance markers were monitored from blood and urine. Protocol biopsies were performed at W3, M3 and M12. Results: Tacrolimus monotherapy resulted in excellent kidney graft function at 12 months (mean Cr 115±22 µmol/L) without proteinuria and normal histology in 10 patients, 3 other patients experienced mild IF/TA score without subclinical rejections. During initial 14 days phase one antibody mediated rejection occurred. Except single case, 6 patients treated with sirolimus monotherapy exhibited significant proteinuria started at 3 month (mean 3.1±2.2 g/day) and subclinical rejections with higher IF/TA score in protocol biopsies and were converted to standard therapy. There was one graft loss in sirolimus group, the rest had satisfactory graft function at 1 year (mean Cr 170±32 µmol/L). Tacrolimus treated patients exhibited after transplantation continuously lower urinary IP-10 levels (<100 pg/mL) than sirolimus treated ones. Lower pretransplant whole blood Toag-1 transcription was associated with the rejection. Recruitment into sirolimus arm was stopped and rest of the patients received tacrolimus. No cancer and opportunistic infections occurred within 12 months. 100% of patients survived first year follow-up. Conclusion: Campath 1H and infliximab induction followed by tacrolimus monotherapy results in first year excellent renal graft function and normal histology. Supported by 6FP EU RISET

Disclosure: All authors have declared no conflicts of interest.