OPTIONS AND OUTCOMES IN THE SENSITIZED KIDNEY RECIPIENT

M.D. Stegall¹, T.S. Diwan², L. Cornell³, J.M. Burns⁴, P.G. Dean², F. Cosio⁵, S. Raghavaiah¹, M.J. Gandhi³, W.K. Kremers³, J.M. Gloor^6
1Of Surgery, Division Of Transplantation, Mayo Clinic, Rochester/UNITED STATES OF AMERICA, ²Surgery, Division Of Transplantation, Mayo Clinic, Rochester/UNITED STATES OF AMERICA, ³Laboratory Medicine And Pathology, Mayo Clinic, Rochester/MN/UNITED STATES OF AMERICA, ⁴Transplantation Surgery, Mayo Clinic, Rochester/UNITED STATES OF AMERICA, ⁵Nephrology, Mayo Clinic, Rochester/UNITED STATES OF AMERICA, ⁶Internal Medicine, Division Of Nephrology And Hypertension, Mayo Clinic, Rochester/UNITED STATES OF AMERICA

Body: Introduction:High levels of donor specific alloantibody (DSA) in sensitized renal transplant recipients commonly lead to acute humoral rejection (AHR), which may result in either acute graft loss or decreased long-term graft survival. We examined whether terminal complement inhibition with the humanized anti-C5 antibody, Eculizumab, could prevent AHR in these recipients. Methods:Renal allograft candidates included had a T / B flow-cytometric cross match channel shift (BFXM) between 450 and 200 (single antigen beads MFI 4000->12,000). Pretransplant PE was performed to achieve a BFXM <300 on the day of transplant. 16 patients received eculizumab at the time of transplant (1200 mg) and weekly thereafter without PE (600 mg) until the BFXM was <250. A historical control group (n=51) received no eculizumab. The primary end point of the study was biopsy-proven AHR < 1 month post-transplant. Follow-up was > 3 months in all patients (eculizumab mean=10.2). Results: Eculizumab treatment led to a decreased incidence of early AHR (6.3% vs 41.2%) including one early graft loss due to AHR in the control group. In patients that developed high levels of DSA (BFXM >350 in first month), all patients in both groups showed evidence of proximal complement activation (C4d+ peritubular capillaries), but only those in the control group showed evidence of histologic injury. Eculizumab treated patients also underwent fewer PEs post-transplant, had less graft dysfunction (defined as maximum change in serum creatinine from post-transplant nadir) and avoided splenectomy. 3 eculizumab patients continued drug >9 weeks due to persistently high DSA. Protocol biopsies showed chronic antibody mediated damage (transplant glomerulopathy) in the control group in 3 patients at 3 months and 9 patients at one year. One patient receiving Eculizumab showed TG and graft dysfunction at 7 months while still receiving drug. Conclusion Terminal complement inhibition with eculizumab significantly reduces the incidence of AHR in sensitized renal transplant recipients, maintains stable allograft function and simplifies the management of these patients by decreasing the need for PE and splenectomy in the post transplant period.

Disclosure: All authors have declared no conflicts of interest.