The use of complement inhibitors in the treatment of acute antibody-mediated rejection (AMR) has not been thoroughly evaluated. We performed a prospective, single-arm, pilot study to assess the efficacy and safety of C1-inhibitor (CI-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute AMR that is non-responsive to conventional therapy.

Kidney recipients with acute AMR that was non-responsive to conventional standardized treatment (plasmaphereses [x4], high-dose IVIG [2 g/kg] repeated every 3 weeks for 3 rounds and rituximab [375 mg per square meter of body-surface area]) were prospectively enrolled between April 1, 2013, and July 1, 2014 (N=6). They received C1-INH (20 U/kg twice weekly) and high-dose IVIG (2 g/kg bw every 3 weeks) for 6 months. C1-INH patients were compared with a historical control group treated with high-dose IVIG alone (N=21). The primary endpoint was allograft function (eGFR) changes between the groups at 6 months after inclusion. Secondary end points included allograft histology, donor-specific anti-HLA antibody (DSA) characteristics and adverse events in the C1-INH group, as evaluated at 6 months after inclusion.

The C1-INH group showed a significant improvement in eGFR compared with the control group: +16.6±9.9% vs. -13.0±33.1% (p=0.01). The mean eGFR at the end of the study was of 45.2±21.3 mL/min/1.73 m² in the C1-INH group vs. 31.7±14.6 in the control group (p=0.08). All patients in the C1-INH group showed an improvement in eGFR between inclusion and study end from 38.7±17.9 mL/min/1.73 m² to 45.2±21.3 mL/min/1.73 m² (p=0.03). There was no change in the histological features in patients in the C1-INH group between the biopsies at inclusion and those obtained at the end of the study, except for a significant decrease in the C4d deposition rate (83% vs 17%, respectively, p=0.04). There was a significant change in anti-HLA DSA C1q-binding status from 6/6 (100%) positive at enrolment to 1/6 (17%) positive at the end of the study (p=0.02). One deep venous thrombosis of a lower limb occurred during follow-up.

C1-inhibitor added to high-dose IVIG may improve allograft function in kidney recipients with non-responsive acute AMR.

CITATION INFORMATION: Lefaucheur C, Viglietti D, Gosset C, Loupy A, Zeevi A, Glotz D. C1-Inhibitor in Acute Antibody-Mediated Rejection Non-Responsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study. Am J Transplant. 2016;16 (suppl 3).

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