title: Exposure to mycophenolic acid better predicts immunosuppressive efficacy than exposure to calcineurin inhibitors in renal transplant patients.
abstract: A time-to-event model was developed to study the predictive factors of immunosuppressive efficacy in renal transplant patients and to investigate longitudinal calcineurin inhibitor (CNI) and mycophenolic acid (MPA) coexposures and patient characteristics as potential covariates. The efficacy end point included acute rejection (AR), graft loss, and death. Data from 222 patients were analyzed: 23 events were observed in 126 patients receiving cyclosporine as compared with 15 events in 96 patients receiving tacrolimus (P = 0.61) in the first 2 years posttransplantation. Each 1-mg·h/l increase of MPA area under the plasma concentration vs. time curve was associated with a 4% decreased risk of an event (hazard ratio (HR) = 0.96; 95% confidence interval (CI): 0.93-0.99). The onset of cytomegalovirus infection/disease significantly increased this risk (HR = 10.9; 95% CI: 6.5-21.7). Within the observed ranges, CNI exposures were not significantly associated with efficacy (i.e., AR, graft loss, and death). This work advocates the avoidance of unnecessary high CNI dosing and puts forward new arguments for MPA concentration monitoring.
authors: 1] INSERM, UMR-S850, Limoges, France [2] Univ Limoges, Limoges, France.
authors: Z
authors: Z
authors: Daher Abdi
authors: 1] INSERM, UMR-S850, Limoges, France [2] Univ Limoges, Limoges, France.
authors: A
authors: A
authors: Prémaud
authors: 1] INSERM, UMR-S850, Limoges, France [2] Univ Limoges, Limoges, France [3] CHU Limoges, Service de Néphrologie, Dialyse et Transplantations, Limoges, France.
authors: M
authors: M
authors: Essig
authors: 1] Univ Limoges, Limoges, France [2] CHU Limoges, Service de Bactériologie-Virologie-Hygiène, Centre National de Référence des Cytomégalovirus, Limoges, France.
authors: S
authors: S
authors: Alain
authors: CHU Limoges, Service de Néphrologie, Dialyse et Transplantations, Limoges, France.
authors: E
authors: E
authors: Munteanu
authors: CHU Limoges, Service de Bactériologie-Virologie-Hygiène, Centre National de Référence des Cytomégalovirus, Limoges, France.
authors: F
authors: F
authors: Garnier
authors: CHU Brest, Service de Néphrologie, Brest, France.
authors: Y
authors: Y
authors: Le Meur
authors: 1] INSERM, UMR-S850, Limoges, France [2] Univ Limoges, Limoges, France [3] CHU Limoges, Service de Pharmacologie, Toxicologie et Pharmacovigilance, Limoges, France.
authors: P
authors: P
authors: Marquet
authors: 1] INSERM, UMR-S850, Limoges, France [2] Univ Limoges, Limoges, France.
authors: A
authors: A
authors: Rousseau
mesh_terms: D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D016015:Logistic Models; D008954:Models, Biological; D015337:Multicenter Studies as Topic; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus