Mycophenolic acid 12-h trough level monitoring in renal transplantation: Association with acute rejection and toxicity

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 (MMIF) 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, biopsyproven 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.