TY - JOUR
T1 - Peritransplant eculizumab does not prevent delayed graft function in deceased donor kidney transplant recipients
T2 - Results of two randomized controlled pilot trials
AU - Schröppel, Bernd
AU - Akalin, Enver
AU - Baweja, Mukta
AU - Bloom, Roy D.
AU - Florman, Sander
AU - Goldstein, Michael
AU - Haydel, Brandy
AU - Hricik, Donald E.
AU - Kulkarni, Sanjay
AU - Levine, Matthew
AU - Mehrotra, Anita
AU - Patel, Anup
AU - Poggio, Emilio D.
AU - Ratner, Lloyd
AU - Shapiro, Ron
AU - Heeger, Peter S.
N1 - Publisher Copyright:
© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Animal models and observational human data indicate that complement, including C5a, pathogenically participates in ischemia reperfusion (IR) injury that manifests as delayed graft function (DGF) following deceased donor kidney transplantation. We report on the safety/efficacy of anti-C5 monoclonal antibody eculizumab (Ecu) administered in the operating room prior to reperfusion, to prevent DGF in recipients of deceased donor kidney transplants in two related, investigator-sponsored, randomized controlled trials. Eight recipients from a single center were enrolled in a pilot study that led to a 19-subject multicenter trial. Together, 27 deceased donor kidney transplant recipients, 16 Ecu-treated and 11 controls, were treated with rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil with or without glucocorticoids, and followed for 6 months. Data analysis showed no epidemiological or transplant-related differences between study arms. Ecu was well tolerated with a similar severe adverse event incidence between groups. The DGF rate did not differ between Ecu-treated (44%) and control (45%, P = 1.0) subjects. Serum creatinine reduction in the first week after transplantation, and graft function up to 180-days post-transplant, were also similar. Ecu administration was safe but did not reduce the rate of DGF in a high-risk population of deceased donor recipients.
AB - Animal models and observational human data indicate that complement, including C5a, pathogenically participates in ischemia reperfusion (IR) injury that manifests as delayed graft function (DGF) following deceased donor kidney transplantation. We report on the safety/efficacy of anti-C5 monoclonal antibody eculizumab (Ecu) administered in the operating room prior to reperfusion, to prevent DGF in recipients of deceased donor kidney transplants in two related, investigator-sponsored, randomized controlled trials. Eight recipients from a single center were enrolled in a pilot study that led to a 19-subject multicenter trial. Together, 27 deceased donor kidney transplant recipients, 16 Ecu-treated and 11 controls, were treated with rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil with or without glucocorticoids, and followed for 6 months. Data analysis showed no epidemiological or transplant-related differences between study arms. Ecu was well tolerated with a similar severe adverse event incidence between groups. The DGF rate did not differ between Ecu-treated (44%) and control (45%, P = 1.0) subjects. Serum creatinine reduction in the first week after transplantation, and graft function up to 180-days post-transplant, were also similar. Ecu administration was safe but did not reduce the rate of DGF in a high-risk population of deceased donor recipients.
KW - clinical research/practice
KW - clinical trial
KW - delayed graft function (DGF)
KW - kidney transplantation/nephrology
UR - http://www.scopus.com/inward/record.url?scp=85077157797&partnerID=8YFLogxK
U2 - 10.1111/ajt.15580
DO - 10.1111/ajt.15580
M3 - Article
C2 - 31452319
AN - SCOPUS:85077157797
SN - 1600-6135
VL - 20
SP - 564
EP - 572
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 2
ER -