How Delayed Graft Function Impacts Exposure to Mycophenolic Acid in Patients After Renal Transplantation.
van Gelder T, Silva HT, et al.Therapeutic Drug Monitoring, 33(2): 155-164, 2011.
Aims
This post hoc analysis aimed to investigate the impact of delayed graft function (DGF) on mycophenolic acid (MPA) exposure in in patients after renal transplantation.
Interventions
Standard-dose mycophenolate mofetil (MMF) versus a MMF dose based on MPA plasma concentration measurements. All patients were given either cyclosporine or tacrolimus and corticosteroids for concomitant immunosuppressive therapy.
Participants
830 renal transplant recipients.
Outcomes
The primary endpoint was the proportion of patients reaching treatment failure. Other outcomes included incidence of DGF, renal function, total and free MPA area under the curve (AUC), incidence of biopsy-proven acute rejection, graft loss, death or discontinuation of MMF therapy by 12 month posttransplantationAdverse events included diarrhea, leukopenia and anemia.
Follow-up
12 months
CET Conclusions
This is a post hoc analysis from the fixed dose/concentration controlled dose of MMF trial (FDCC trial). Delayed graft function occurred in 23% of the approximately 800 patients who participated in this trial. There was no difference in the incidence of DGF whether the patients received cyclosporine or tacrolimus treatment. Biopsy proven acute rejection at 12 months was higher in the patients with DGF and those patients with DGF had a lower dose corrected MPA AUC on days 3 and 10. This would suggest that patients who were receiving MMF and who have delayed graft function should receive higher dosing of MMF in the early days after transplantation.
Data analysis
Strict intention-to-treat analysis
Quality notes
This is a post hoc analysis of a previous publication of the same RCT: van Gelder T, Silva HT, de Fijter JW, et al. Comparing mycophenolate mofetil regimens for de novo renal transplant recipients: the Fixed-Dose Concentration-Controlled trial. Transplantation. 2008; 86:1043–1051. The methodological quality assessment was based on the previous publication.
Trial registration
NCT00166244 (ClinicalTrials.gov)