Targeted donor complement blockade after brain death prevents delayed graft function in a nonhuman primate model of kidney transplantation. Issue 6 (20th February 2020) - Danobeitia, Juan S.
Abstract : Delayed graft function (DGF) in renal transplant is associated with reduced graft survival and increased immunogenicity. The complement‐driven inflammatory response after brain death (BD) and posttransplant reperfusion injury play significant roles in the pathogenesis of DGF. In a nonhuman primate model, we tested complement‐blockade in BD donors to prevent DGF and improve graft survival. BD donors were maintained for 20 hours; kidneys were procured and stored at 4°C for 43‐48 hours prior to implantation into ABO‐compatible, nonsensitized, MHC‐mismatched recipients. Animals were divided into 3 donor‐treatment groups: G1 ‐ vehicle, G2 ‐ rhC1INH+heparin, and G3 ‐ heparin. G2 donors showed significant reduction in classical complement pathway activation and decreased levels of tumor necrosis factor α and monocyte chemoattractant protein 1. DGF was diagnosed in 4/6 (67%) G1 recipients, 3/3 (100%) G3 recipients, and 0/6 (0%) G2 recipients ( P = .008). In addition, G2 recipients showed superior renal function, reduced sC5b‐9, and reduced urinary neutrophil gelatinase–associated lipocalin in the first week posttransplant. We observed no differences in incidence or severity of graft rejection between groups. Collectively, the data indicate that donor‐management targeting complement activation prevents the development of DGF. Our results suggest a pivotal role for complement activation in BD‐induced renal injury and postulate complement blockade as a promising strategy for the prevention of DGF after transplantation. Abstract : Using a nonhuman primate model of brain death followed by renal allotransplantation, the authors demonstrate that donor treatment with a recombinant C1‐inhibitor has a protective effect on the graft and significantly reduces the progression to delayed graft function in the recipient. See the editorial from Bossard and Thuillier on page 1473 .