Background: Delayed graft function (DGF)in kidney allograft recipients is traditionally defined as need for dialysis during the first week after transplantation. DGF is related to ischemia reperfusion injury (IRI) that impacts long-term allograft function and survival. There are no approved therapies for preventing IRI/DGF. Complement activation induced by IRI may induce DGF. Data from animal models indicate beneficial effects for prevention of IRI/DGF in animals treated with the complement inhibitor, C1 esterase inhibitor (C1INH). Here, we investigated the ability of (C1INH, Berinert, CSL-Behring) to prevent IRI/DGF in kidney transplant recipients receiving high risk donor kidneys. Methods: 70 patients receiving cadaver kidney transplants at risk for DGF were randomized to receive C1INH 50 U/kg (#35) or placebo (#35) intra-operatively and 24 hours later. The primary end point was need for hemodialysis during the first week post-transplant. Assessments of renal function (one year) and dialysis dependency (one month) were accomplished. Complicatons and safety of therapy was recorded. Patients were followed for 1 year. Results: Patients randomized to C1INH and placebo exhibited similar characteristics with no significant differences in cold-ischemia time or other risk factors for DGF. C1INH did not result in reduced number of dialysis sessions at 1 week post-transplant, but significantly fewer dialysis sessions(p=0.0232)were required 2-4 weeks post-transplant. Patients at highest risk for DGF (KDPI >85) benefited most from C1INH therapy. Significantly better renal function was seen at one year in C1INH patients (p=0.018). No significant adverse events were noted with C1INH. Conclusion: Although the primary end point was not met, significant reductions in the need for dialysis two weeks post-transplant and improvements in long-term allograft function were seen with C1INH treatment. Inhibition of the classic and MBL/MASP-2 complement activation pathways may improve utility and function of high KDPI kidneys. Larger placebo-controlled, multi-center trials are needed.

CITATION INFORMATION: Jordan S., Choi J., Aubert O., Haas M., Loupy A., Huang E., Peng A., Kim I., Sethi S., Louie S., Puliyanda D., Vo A. A Phase I/II, Double-Blind, Placebo-Controlled Study Assessing Safety and Efficacy of C1 Esterase Inhibitor for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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