SP731EXTRACORPOREAL PHOTOPHERESIS AS A WAY TO REDUCE IMMUNOSUPPRESSIVE LOAD IN LATE PERIOD AFTER RENAL TRANSPLANTATION

Abstract

INTRODUCTION AND AIMS: x METHODS: A prospective randomized cohort study in 30 pairs of recipients has been conducted. One donor kidney was transplanted to a patient of the study group, the other-to the patient of the control group. The study group was treated with the immunosuppressive therapy (Tac,MMF and prednisolone) combined with 15 sessions of extracorporeal photopheresis (ECP) within six months; control group received immunosuppressive therapy only. We tried to minimize the immunosuppressive therapy: reduce the C0 concentration of Tac and complete withdraw prednisolone. If suspected of rejection, a graft biopsy was performed. Primary endpoint: loss of graft function (including death). Secondary outcomes: the number of acute rejections and infections. For the adjusted risk assessment, Poisson regression was used. We also evaluated the immunological parameters in one year after transplantation. The mean follow-up period was 57.869.2 months. RESULTS: The adjusted risk of graft loss was higher in the control group compared to the study group: incidence rate ratio (IRR) 3.209 (95%CI 1.031, 11.8), p=0.0371. The causes of graft loss in the study group (N=4): 1 death with a functioning graft, 1 recurrent focal segmental glomerulosclerosis (FSGS), 1 acute antibody-mediated rejection (ABMR) and 1 chronic allograft nephropathy (CAN). The causes of graft loss in the control group (N=10): 2 death with a functioning graft, 1 recurrent FSGS, 1 IgA nephropathy, 2 acute ABMR, 2 chronic active ABMR, 2 CAN. All the deaths were caused by infectious complications. Risk of infections was higher in the control group vs. study group: IRR 3.594 (95%CI 1.333, 11.1), p=0.0086. Infectious complications in the study group (N=5): 2 acute respiratory infections, 2 graft pyelonephritis, 1 mesenteric thrombosis and peritonitis. Infectious complications in the control group (N=14): 5 acute respiratory infections, 3 graft pyelonephritis, 1 tuberculosis, 1 pancreatic necrosis, 1 reactivation of hepatitis B with fulminant hepatic failure, 1 de novo bronchoectatic disease, 1 pyelonephritis and paranephritis of native kidney, 1 unidentified cause.In many cases, infectious complications were associated with the treatment of acute rejection. Risk of acute rejection was higher in the control group vs. study group: IRR 2.425 (95%CI 1.089, 5.6±9), p=0.0265. Morphological and immunohistochemical evaluation was performed in all cases.Stable function of the graft allowed to safely reduce immunosuppressive load in 22 patients of the study group and 14 patients of the control group. C0 tacrolimus concentration was lower in the study group after the third year (fig. 1).ECP reduces the fraction of effector CD8 cells and increases the fraction of FOXP3+ Tregs. Moreover ECP reduces the expression of CD28 on T-helpers. It is creates the background for a preferential interaction of CD80/86 on antigen-presenting cell with a CTLA4 on T-helper. As result the antigen-specific second costimulatory signal switching into the co-inhibitory signal. CONCLUSIONS: ECP a promising method of adjuvant immunotherapy, which can be helpful in safe reduction of immunosuppressive load. This method reduces the risk of graft loss and infections (Figure presented).