title: Mycophenolic acid 12-h trough level monitoring in renal transplantation: association with acute rejection and toxicity.
abstract: Studies of renal transplantation utilizing trough plasma level monitoring of mycophenolic acid (MPA) have shown inconsistent associations with toxicity and rejection. In this study, 5600 12-h trough MPA samples from 121 renal transplant recipients immunosuppressed with mycophenolate mofetil (MMF) and tacrolimus in a steroid sparing protocol (steroids for 7 days only) were sequentially analyzed. Higher MPA levels were associated with lower hemoglobin concentrations and anemia (hemoglobin <10 g/dL). Similarly, higher MPA levels were associated with lower total white cell counts and an increased incidence of leucopenia (total white cell count <4.0 x 10(9)/L). Hypoalbuminemia and renal impairment were also associated with hemotoxicity. MMF-associated diarrhea and viral infection were associated with higher MPA levels. Conversely, biopsy-proven acute rejection within the first month post-transplantation was associated with lower MPA levels. Anti-CD25 antibody induction was also associated with reduced rejection rates. No association was seen between MPA levels and platelet count, thrombocytopenia or bacterial infection. An MPA level of 1.60 mg/L early post-transplantation best discriminated patients with and without rejection, and an MPA level of 2.75 mg/L best discriminated patients with and without toxicity later post-transplantation.
authors.affiliation: Renal and Transplant Units, St. Mary's Hospital, Paddington, London W2 1NY, UK. richard.borrows@uhb.nhs.uk
authors.forename: R
authors.initials: R
authors.lastname: Borrows
authors.forename: G
authors.initials: G
authors.lastname: Chusney
authors.forename: M
authors.initials: M
authors.lastname: Loucaidou
authors.forename: A
authors.initials: A
authors.lastname: James
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: J V
authors.initials: JV
authors.lastname: Tromp
authors.forename: J
authors.initials: J
authors.lastname: Owen
authors.forename: T
authors.initials: T
authors.lastname: Cairns
authors.forename: M
authors.initials: M
authors.lastname: Griffith
authors.forename: N
authors.initials: N
authors.lastname: Hakim
authors.forename: A
authors.initials: A
authors.lastname: McLean
authors.forename: A
authors.initials: A
authors.lastname: Palmer
authors.forename: V
authors.initials: V
authors.lastname: Papalois
authors.forename: D
authors.initials: D
authors.lastname: Taube
mesh_terms: D000328:Adult; D001424:Bacterial Infections / Q000175:diagnosis; D001853:Bone Marrow / Q000276:immunology; D003967:Diarrhea / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood*; D016030:Kidney Transplantation; D007958:Leukocyte Count; D007970:Leukopenia / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000097:blood*; D010976:Platelet Count; D016559:Tacrolimus / Q000097:blood; D013921:Thrombocytopenia / Q000175:diagnosis; D014777:Virus Diseases / Q000175:diagnosis
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus