Peritransplant eculizumab does not prevent delayed graft function in deceased donor kidney transplant recipients: Results of two randomized controlled pilot trials

Abstract

Funding information AlAnimal 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

Ischemia and Reperfusion Injury in Kidney Transplantation: Relevant Mechanisms in Injury and Repair

“…Again, the safety profile was good but pre-treatment with eculizumab had no effect on the incidence of DGF. Groups in these studies, however, were rather small [162]. Another anti-C5 antibody Tesidolumab (LFG-316, MorphoSys, Novartis) has currently entered phase 1 studies (NCT02878616).…”

Complement, a Therapeutic Target in Diabetic Kidney Disease

“…Eculizumab has also been used with promising results to treat C3 glomerulopathies ( 74 , 75 ) and antibody-mediated kidney transplant rejection ( 76 , 77 ). It has also been tested, but with no success, to prevent delayed kidney graft function (DGF) after transplantation ( 78 ). Several clinical studies are ongoing for other conditions, including HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count - NCT04103489), and Guillain-Barre syndrome (NCT02029378).…”

Review: Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation

“…Kaabak et al [24] demonstrated that a single dose one hour prior to graft reperfusion in pediatric kidney recipients had better early graft function and biopsy scores, but the incidence of graft rejection did not differ between groups. A later study in 2019 also showed that the administration of eculizumab prior to organ reperfusion showed no difference in delayed graft, function, and survival at 6 months [25]. Another critical component of the complement cascade is C3, which can be produced by many tissues.…”