title: Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients.
abstract: Sensitized renal transplant recipients with high levels of donor-specific alloantibody (DSA) commonly develop antibody-mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti-C5 antibody, eculizumab, in the prevention AMR in renal transplant recipients with a positive crossmatch against their living donor. The incidence of biopsy-proven AMR in the first 3 months posttransplant in 26 highly sensitized recipients of living donor renal transplants who received eculizumab posttransplant was compared to a historical control group of 51 sensitized patients treated with a similar plasma exchange (PE)-based protocol without eculizumab. The incidence of AMR was 7.7% (2/26) in the eculizumab group compared to 41.2% (21/51) in the control group (p = 0.0031). Eculizumab also decreased AMR in patients who developed high levels of DSA early after transplantation that caused proximal complement activation. With eculizumab, AMR episodes were easily treated with PE reducing the need for splenectomy. On 1-year protocol biopsy, transplant glomerulopathy was found to be present in 6.7% (1/15) eculizumab-treated recipients and in 35.7% (15/42) of control patients (p = 0.044). Inhibition of terminal complement activation with eculizumab decreases the incidence of early AMR in sensitized renal transplant recipients (ClincalTrials.gov number NCT006707).
authors.affiliation: William J. von Liebig Transplant Center, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN, USA. stegall.mark@mayo.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Stegall
authors.forename: T
authors.initials: T
authors.lastname: Diwan
authors.forename: S
authors.initials: S
authors.lastname: Raghavaiah
authors.forename: L D
authors.initials: LD
authors.lastname: Cornell
authors.forename: J
authors.initials: J
authors.lastname: Burns
authors.forename: P G
authors.initials: PG
authors.lastname: Dean
authors.forename: F G
authors.initials: FG
authors.lastname: Cosio
authors.forename: M J
authors.initials: MJ
authors.lastname: Gandhi
authors.forename: W
authors.initials: W
authors.lastname: Kremers
authors.forename: J M
authors.initials: JM
authors.lastname: Gloor
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003182:Complement C5 / Q000037:antagonists & inhibitors; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D051056:Complement Inactivating Agents; D007518:Isoantibodies; C481642:eculizumab