Backtable Intra-Arterial Administration of C1 Esterase Inhibitor to Deceased Donor Kidney Allografts Improves Post-Transplant Allograft Function: Results of a Randomized Double-Blind Placebo-Controlled Clinical Trial.

Abstract

Ischemia-reperfusion injury (IRI) commonly causes delayed graft function (DGF) after kidney transplantation and is associated with poorer graft function and lower allograft survival. Activation of the lectin complement pathway is one mediator of IRI. In this randomized double-blind placebo-controlled pilot study, we tested whether pre-implantation intragraft administration of C1 esterase inhibitor (C1INH, a lectin/classical pathway inhibitor) into deceased donor organs improves graft function and/or reduces DGF. Forty patients were randomized 1:1 to receive allografts treated with 500 units C1INH or placebo (normal saline) into the transplant renal artery during back-table preparation. We observed no effect on DGF, but recipients of C1INH-treated allografts showed higher eGFR vs. placebo at 6 months (C1INH median: 55 ml/min/1.73 m2, IQR: 42-63; placebo median: 39 ml/min/1.73 m2, IQR 34-50; p=0.02) and 30 months (C1INH median: 54 ml/min/1.73 m2, IQR: 47-66; placebo median: 43 ml/min/1.73 m2, IQR 38-51; p=0.03) without differences in adverse events. Analysis of post-reperfusion biopsies showed positive intra-arterial C1INH staining and reduced C4d staining in C1INH-treated grafts vs controls. Post-transplant serum MBL and classical pathway activity and bradykinin levels did not differ between study arms. We conclude that this treatment strategy improves allograft function independent of DGF, likely via local intragraft complement inhibition. Clinical trial registration number: NCT04696146.