title: Early adequate mycophenolic acid exposure is associated with less rejection in kidney transplantation.
abstract: This study examines the importance of early mycophenolic acid (MPA) exposure in the cyclosporine- and mycophenolate mofetil (MMF)-treated kidney transplant population. We prospectively evaluated 94 first solitary kidney transplant patients treated with cyclosporine (Neoral), MMF, and prednisone. Basiliximab was also given to 72 recipients. MPA exposure was measured by HPLC using a limited sampling estimate of 12 h area under the curve (AUC [0-12]) within the first week. Efficacy was determined by the occurrence of acute rejection and toxicity by the need to reduce MMF doses within the first 3 months post-transplantation. Acute rejection was observed in 14 (15%) and MMF toxicity in 27 (29%). Receiver operator curve analysis shows that MPA AUC [0-12] on day 3 was predictive of efficacy (c = 0.72, p = 0.007) but not toxicity (c = 0.57, p = 0.285). A separate analysis of only patients on basiliximab shows that the MPA AUC [0-12] on day 3 was also predictive of efficacy (c = 0.80, p = 0.01). Therefore early adequate exposure to MPA by day 3 is associated with low acute rejection but cannot predict toxicity. Adequate MPA exposure is also important with basiliximab induction therapy.
authors.affiliation: Department of Medicine, Capital Health and Dalhousie University, Halifax, Nova Scotia, Canada. bkiberd@dal.ca
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Kiberd
authors.forename: Joseph
authors.initials: J
authors.lastname: Lawen
authors.forename: Albert D
authors.initials: AD
authors.lastname: Fraser
authors.forename: Tammy
authors.initials: T
authors.lastname: Keough-Ryan
authors.forename: Philip
authors.initials: P
authors.lastname: Belitsky
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000077552:Basiliximab; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D009173:Mycophenolic Acid