title: Belatacept and Eculizumab for Treatment of Calcineurin Inhibitor-induced Thrombotic Microangiopathy After Kidney Transplantation: Case Report.
abstract: Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome. Belatacept, an inhibitor of T cell costimulatory protein CTLA-4 has been used in immunosuppression strategies aimed at minimization of CNI. Here we report the first case of treatment of CNI-associated TMA/hemolytic uremic syndrome with withdrawal of tacrolimus and initiation of both belatacept and eculizumab. The case describes a favorable clinical course for both graft and patient, and is accompanied by a review of the literature.
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: J
authors.initials: J
authors.lastname: Merola
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut. Electronic address: peter.yoo@yale.edu.
authors.forename: P S
authors.initials: PS
authors.lastname: Yoo
authors.affiliation: Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
authors.forename: J
authors.initials: J
authors.lastname: Schaub
authors.affiliation: Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
authors.forename: J D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: M I
authors.initials: MI
authors.lastname: Rodriguez-Davalos
authors.affiliation: Department of Pharmacy, Yale-New Haven Hospital, New Haven, Connecticut.
authors.forename: E
authors.initials: E
authors.lastname: Tichy
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: D C
authors.initials: DC
authors.lastname: Mulligan
authors.affiliation: Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
authors.forename: W
authors.initials: W
authors.lastname: Asch
authors.affiliation: Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
authors.forename: R
authors.initials: R
authors.lastname: Formica
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: M
authors.initials: M
authors.lastname: Kashgarian
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, Connecticut.
authors.forename: S
authors.initials: S
authors.lastname: Kulkarni
mesh_terms: D000069594:Abatacept / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000150:complications; D065095:Calcineurin Inhibitors / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D010956:Plasmapheresis / Q000009:adverse effects; D011183:Postoperative Complications / Q000139:chemically induced; D057049:Thrombotic Microangiopathies / Q000139:chemically induced / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000069594:Abatacept; C481642:eculizumab