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

Am J Transplant. 2006 Jan;6(1):121-8. doi: 10.1111/j.1600-6143.2005.01151.x.

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.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Bacterial Infections / diagnosis
  • Bone Marrow / immunology
  • Diarrhea / diagnosis
  • Dose-Response Relationship, Drug
  • Drug Monitoring
  • Female
  • Graft Rejection / diagnosis*
  • Humans
  • Immunosuppression
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood*
  • Kidney Transplantation*
  • Leukocyte Count
  • Leukopenia / diagnosis
  • Male
  • Middle Aged
  • Monitoring, Physiologic
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / blood*
  • Platelet Count
  • Tacrolimus / blood
  • Thrombocytopenia / diagnosis
  • Virus Diseases / diagnosis

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus