RELATE: Relationship of limited sampling strategy and adverse effects of mycophenolate mofetil in pediatric renal transplant patients

Pediatr Transplant. 2019 Mar;23(2):e13355. doi: 10.1111/petr.13355. Epub 2019 Jan 28.

Abstract

MMF, a prodrug converted to the active form MPA, is an immunosuppressant used to prevent rejection in solid organ transplant recipients. MPA exposure, defined by AUC, can be estimated using limited sampling strategies (LSS). The relationship between MPA AUC and clinical outcomes has not been studied in pediatrics. The objectives were to describe the relationship of MPA AUC (estimated via LSS) with adverse effects and rates of rejection, and to compare clinical outcomes between different MPA monitoring practices. Descriptive statistics were used to summarize demographics, adverse effects, and rejection. Thirty-three patients (91 trough concentrations and 12 LSS sets) aged 2-20 years old were included. The estimated median MPA AUCs (David-Neto and Filler) were higher for those who did not have any adverse effects reported (65.85 and 85.05 mg*h/L, respectively) compared to those who had an adverse effect (60.75 and 54.2 mg*h/L, respectively). The median trough concentration when no adverse effects occurred was comparable to when adverse effects occurred. The median MPA AUC at which rejection occurred was lower than in those without rejection. The median trough concentration at which rejection occurred was higher than those without rejection (3.1 mg/L compared to 1.9 mg/L). The occurrence of adverse effects or rejection was not shown to be related to measured MPA trough or AUC outside of the target therapeutic range. The value of MPA concentration monitoring remains unclear; therefore, the practice of monitoring MPA AUC by LSS or trough concentrations should be reconsidered.

MeSH terms

  • Adolescent
  • Area Under Curve*
  • Child
  • Child, Preschool
  • Drug Monitoring / methods*
  • Female
  • Graft Rejection / diagnosis
  • Graft Rejection / epidemiology
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Male
  • Mycophenolic Acid / adverse effects*
  • Mycophenolic Acid / pharmacokinetics*
  • Mycophenolic Acid / therapeutic use
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid