title: C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.
abstract: Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR.
authors.affiliation: Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.|Paris Translational Research Center for Organ Transplantation, INSERM, UMR-S970, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Viglietti
authors.affiliation: Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Gosset
authors.affiliation: Paris Translational Research Center for Organ Transplantation, INSERM, UMR-S970, Paris, France.|Department of Kidney Transplantation, Necker Hospital, Assitance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Loupy
authors.affiliation: Department of Pharmacy, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Deville
authors.affiliation: Department of Pathology, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Verine
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: A
authors.initials: A
authors.lastname: Zeevi
authors.affiliation: Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Glotz
authors.affiliation: Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.|Paris Translational Research Center for Organ Transplantation, INSERM, UMR-S970, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lefaucheur
mesh_terms: D000328:Adult; D050718:Complement C1 Inhibitor Protein / Q000627:therapeutic use*; D051056:Complement Inactivating Agents / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007518:Isoantibodies / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies