Targeted Donor Complement Blockade After Brain‐Death Prevents Delayed Graft Function In A Non‐Human Primate Model Of Kidney Transplantation

American Journal of Transplantation
Targeted Donor Complement Blockade After Brain‐Death Prevents Delayed Graft Function In A Non‐Human Primate Model Of Kidney Transplantation

Abstract

Delayed graft function (DGF) in renal transplantation is associated with reduced graft survival and increased immunogenicity. The complement‐driven inflammatory response after brain death (BD) and post‐transplant reperfusion injury play significant roles in the pathogenesis of DGF. In a non‐human primate model, we tested complement‐blockade in BD donors to prevent DGF and improve graft survival. BD donors were maintained 20‐hours, kidneys were procured and stored at 4°C for a 43–48 hours prior to implantation into ABO‐compatible, non‐sensitized, MHC‐mismatched recipients. Animals were divided into three different donor‐treatment groups: G1‐Vehicle, G2‐rhC1INH+heparin, and G3‐heparin only. G2 donors showed significant reduction in classical complement pathway activation and decreased levels of TNFα and MCP‐1. DGF was diagnosed in 4/6 (67%) G1‐recipients, 3/3 (100%) of G3‐recipients, and 0/6 (0%) of G2‐recipients (p=0.008). In addition, G2‐recipients showed superior renal function, reduced sC5b‐9, and reduced urinary NGAL in the first week post‐transplant. 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.

Source: American Journal of Transplantation

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