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| |  Early Exposure to Mycophenolic Acid Decreases Rate of Acute Rejection in Tacrolimus-Treated Kidney Transplant Recipients: Presented at ATC By Cheryl Lathrop BOSTON -- June 3, 2009 -- Early adequate mycophenolic acid (MPA) exposure is significantly associated with less acute rejection (AR) in kidney transplant recipients treated with tacrolimus (TAC), according to a study presented on May 31 at the 2009 American Transplant Congress (ATC). Bryce Kiberd, MD, QEII Health Sciences Centre, Halifax, Nova Scotia, and colleagues investigated whether early adequate MPA exposure (exceeding the MPA therapeutic level of 30 mg.h/L) is associated with less acute rejection by 6 months post-transplant in TAC- and prednisone-treated patients. They also sought to determine whether a full MPA area under the curve (AUC) correlated well with a limited sampling strategy (LSS) within the first week post transplant. The cohort analysis consisted of 135 patients who were part of the randomised, controlled Study of Mycophenolate Mofetil in Recipients of Kidney Transplants (CLEAR Study) to determine whether higher initial doses of mycophenolate mofetil (MMF) would increase the proportion of patients with adequate MPA exposure. The loading dose arm received MMF 3 g on days 1 to 5, and then 2 g daily; the standard dose arm received MMF 2 g daily. TAC was adjusted to trough levels of 8 to 15 ng/mL; all patients received prednisone; and approximately 85% received an interleukin-2 receptor blocker. Full MPA-AUCs were taken on day 3 and day 5 (0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours). AR was defined as biopsy-proven, suspected, or treated. Results were reported for the modified intent to treat patients who had measured AUCs. Patients with subtherapeutic MPA-AUC levels (<30 mg.h/L) at day 5 were significantly more likely to have an AR episode compared with patients with therapeutic MPA-AUC levels (>=30 mg.h/L) at day 5 (50.0% vs 15.5%, P = .0047). The c-statistic for day 5 MPA-AUC and AR was significant (c = 0.704, P = .0138). The best cut point for AR was a day 5 MPA-AUC of 40 mg.h/L (57% sensitivity, 71% specificity). The analysis found a strong correlation between both methods for calculating MPA-AUCs (r = 0.83 on day 3, P < .0001; r = 0.81 on day 5, P < .0001). Both full and LSS MPA-AUCs on day 5 predicted AR, with only slight differences in the optimal cut point (>=30 or 40 mg.h/L). Patients with early MPA exposures >60 mg.h/L did not experience greater toxicity or more adverse events. [Presentation title: The Association of Early MPA Exposure and Patient Outcomes: A Cohort Analysis of the CLEAR Study. Abstract 1134.]
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