title: Toxicity versus rejection--or why conversions between cyclosporine A and FK506 were performed after liver transplantation.
abstract: The introduction of cyclosporine A (CsA) and FK506 significantly improved the outcome of liver transplantation. However, the postoperative course and outcome of liver transplant recipients in still compromised by rejection, over-immunosuppression-induced infection and immunosuppression-associated toxicity. In the present study, we evaluated the reason for conversion between immunosuppressive regimens in 121 patients, 60 treated with FK506 and 61 patients treated with CsA-based immunosuppression. Five patients treated primarily with CsA (8.3%) were converted to FK506 therapy because of refractory acute of chronic rejection within 12 months following liver transplantation (LTX). In 2 patients, conversion was performed after Re-LTX. In 4 of these 5 patients, rejection was successfully treated according to histological and laboratory investigations, while in the remaining patient, graft function improved with persisting histological evidence of chronic rejection. Moderate and severe neurologic symptoms during the early postoperative period, i.e. organic brain syndromes (OBS), seizures, hemiparesis, dysphasia, dysathria and cerebellar symptoms were observed in 21.3% of patients treated with FK506 and in 11.7% of patients treated with CsA (p = n.s.). Five patients treated primarily with FK506 were converted to CsA due to severe neurotoxicity. Early postoperative renal insufficiency was observed to a similar extent with 42.6% of FK506- and 36.7% of CsA-treated patients. 8.3% of FK506-treated patients and 11.7% of CsA-treated patients required hemodialysis (p = n.s.) There patients were converted from FK506 to CsA due to persisting renal insufficiency. Moderate and severe neurologic symptoms were observed more frequently under treatment with FK506 than CsA, and all conversions from FK506 to CsA (13.3%) were performed because of neuro- or nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, Free University of Berlin, Universitätsklinikum Rudolf Vichow, Germany.
authors.forename: K P
authors.initials: KP
authors.lastname: Platz
authors.forename: A R
authors.initials: AR
authors.lastname: Mueller
authors.forename: S
authors.initials: S
authors.lastname: Jonas
authors.forename: G
authors.initials: G
authors.lastname: Blumhardt
authors.forename: W O
authors.initials: WO
authors.lastname: Bechstein
authors.forename: H
authors.initials: H
authors.lastname: Lobeck
authors.forename: H L
authors.initials: HL
authors.lastname: Neuhaus
mesh_terms: D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D006084:Graft Rejection / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D009422:Nervous System Diseases / Q000209:etiology; D015996:Survival Rate; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus