Inadequate mycophenolic acid exposure and acute rejection in kidney transplantation

Transplant Proc. 2009 Jul-Aug;41(6):2104-5. doi: 10.1016/j.transproceed.2009.05.015.

Abstract

Introduction: The clinical utility of predose levels of mycophenolic acid (MPA) monitoring among patients treated with mycophenolate mofetil (MMF) has been questioned. The aim of this study was to evaluate the impact of adequate MPA levels in the incidence of acute rejection episodes among a cohort of kidney transplant recipients.

Material and methods: In this retrospective study of 314 consecutive cases treated with tacrolimus, MMF, and steroids, evaluated 12-hour trough MPA samples during the first week as well as at 1, 3, 6, and 12 months as median values.

Results: During the first week, the median values of MPA were 1.6 microg/mL (p25-75 0.7-2.7 microg/mL) on mean doses of 1.84 +/- 0.38 g/d. The incidence of acute rejection was 28%. The mean MPA levels during the first week were significantly lower among patients who developed rejection than in nonrejectors (1.5 +/- 0.1 vs 2.1 +/- 0.1 microg/mL; P < .001). There were no significant differences in trough tacrolimus levels between rejectors and nonrejectors (11.2 +/- 0.4 vs 11.6 +/- 1.2 microg/mL; P < .78). Logistic regression analysis showed that one of the predictive factors of acute rejection was a 12-hour trough MPA <1.6 microg/mL (relative risk [RR] 2.6; CI [confidence interval] 95% 1.6-4.3; P < .001).

Conclusions: Adequate MPA exposure is important to prevent acute rejection. Taking into account that the routine measurement of the area under the curve of MPA is impractical, at least the follow-up of trough MPA levels may help in the management of renal transplant recipients.

MeSH terms

  • Acute Disease
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Graft Rejection / epidemiology*
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Mycophenolic Acid / pharmacokinetics
  • Mycophenolic Acid / therapeutic use*
  • Retrospective Studies

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid