| Autor: |
Gaston RS; University of Alabama at Birmingham, Birmingham, AL, USA. rgaston@uab.edu, Kaplan B, Shah T, Cibrik D, Shaw LM, Angelis M, Mulgaonkar S, Meier-Kriesche HU, Patel D, Bloom RD |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2009 Jul; Vol. 9 (7), pp. 1607-19. Date of Electronic Publication: 2009 May 20. |
| DOI: |
10.1111/j.1600-6143.2009.02668.x |
| Abstrakt: |
Mycophenolate mofetil (MMF) was developed with cyclosporine as a fixed-dose immunosuppressant. More recent data indicate a relationship between mycophenolic acid (MPA) exposure in individuals and clinical endpoints of rejection and toxicity. This 2-year, open-label, randomized, multicenter trial compared the efficacy and safety of concentration-controlled MMF (MMF(CC)) dosing with a fixed-dose regimen in 720 kidney recipients. Patients received either (A) MMF(CC) and reduced-level calcineurin inhibitor (MMF(CC)/CNI(RL)); (B) MMF(CC) and standard-level CNI (MMF(CC)/CNI(SL)); or (C) fixed-dose MMF and CNI(SL) (MMF(FD)/CNI(SL)). Antibody induction and steroid use were according to center practice. The primary endpoint was noninferiority (alpha= 0.05) of group A versus group C for treatment failure (including biopsy-proven acute rejection [BPAR], graft loss and death) at 1 year. Although mean CNI trough levels in group A did not reach the prespecified targets, they were statistically lower than those in groups B and C (p < or = 0.01 for each comparison). BPAR rates (8.5%) were low across groups. Group A had 19% fewer treatment failures (23% vs. 28%, p = 0.18). MMF doses were highest (p < 0.05), with withdrawals for adverse events the fewest (p = 0.02), in group A. Of the 80% of subjects taking tacrolimus (Tac), those with higher MPA exposure had significantly less rejection (p < 0.001) and diarrhea correlated with Tac, but not with MPA levels. Thus, MMF(CC) with low-dose CNI resulted in outcomes not inferior to those with standard CNI exposure and MMF(FD), indicating potential utility of MMF(CC) in CNI-sparing regimens. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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