title: Basiliximab widens the therapeutic window for AUC-monitored neoral therapy early after kidney transplantation.
abstract: Early adequate cyclosporine exposure has been shown to predict low acute rejection. Recently basiliximab induction has been added to immunosuppressive regimens to further reduce rejection. The aim of this study was to determine the importance of achieving the early cyclosporine therapeutic threshold with basiliximab induction. A retrospective analysis of first cadaver and nonidentical living donor transplant recipients treated with or without basiliximab induction was performed. All patients (n = 170) received neoral, mycophenolate mofetil, and prednisone. The cyclosporine absorption profile was measured on day 3. Adequate cyclosporine exposure was defined as area under the curve (AUC) 0-4: >4400 microg x h/L at day 3. The primary outcome was acute rejection (AR) within the first 6 month. In the no basiliximab (control) group, AR occurred in 22% (17/78) of recipients and was strongly associated with low cyclosporine exposure on day 3. AR occurred in 39% (9/23) with cyclosporine AUC0-4 < 4400 microg x h/L compared with 15% (8/55) with AUC0-4 > 4400 microg x h/L (P =.016). In the basiliximab group, AR occurred in only 9% (8/92) of recipients and did not correlate with cyclosporine exposure. AR occurred in 8% (2/24) with cyclosporine AUC0-4 < 4400 microg x h/L compared with 9% (6/68) with AUC0-4 > 4400 microg x h/L (P =.94). Achieving cyclosporine therapeutic targets by day 3 may not be required when anti-IL2 induction is used.
authors: Kidney Transplant program, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
authors: F
authors: F
authors: Balbontin
authors: B
authors: B
authors: Kiberd
authors: D
authors: D
authors: Singh
authors: J
authors: J
authors: Squires
authors: A
authors: A
authors: Fraser
authors: P
authors: P
authors: Belitsky
authors: J
authors: J
authors: Lawen
mesh_terms: D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D000077552:Basiliximab; D002102:Cadaver; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins; D012189:Retrospective Studies; D014019:Tissue Donors
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab