Early Steroid Withdrawal and Optimization of Mycophenolic Acid Exposure in Kidney Transplant Recipients Receiving Mycophenolate Mofetil

被引:26
作者
Le Meur, Yannick [1 ]
Thierry, Antoine [2 ]
Glowacki, Francois [3 ]
Rerolle, Jean-Philippe [4 ]
Garrigue, Valerie [5 ]
Ouali, Nacera [6 ]
Heng, Anne-Elisabeth [7 ]
Delahousse, Michel [8 ]
Albano, Laeticia [9 ]
Lang, Philippe [10 ]
Couzi, Lionel [11 ]
Jaureguy, Maite [12 ]
Lebranchu, Yvon [13 ]
Mousson, Christiane [14 ]
Glotz, Denis [15 ]
Kessler, Michele [16 ]
Vrtovsnik, Francois [17 ]
Rouanet, Stephanie [18 ]
Tagieva, Nailya [18 ]
Kamar, Nassim [19 ]
机构
[1] Univ Hosp, Dept Nephrol, Brest, France
[2] Univ Hosp, Dept Nephrol, Poitiers, France
[3] Univ Hosp, Dept Nephrol, Lille, France
[4] Dept Nephrol & Transplantat, Limoges, France
[5] Univ Hosp, Dept Nephrol Transplantat & Peritoneal Dialysis, Montpellier, France
[6] Tenon Hosp, Dept Nephrol & Transplantat, Paris, France
[7] Univ Hosp, Dept Nephrol, Clermont Ferrand, France
[8] Foch Hosp, Dept Nephrol & Transplantat, Suresnes, France
[9] Univ Hosp, Dept Nephrol & Transplantat, Nice, France
[10] Henri Mondor Hosp, Dept Nephrol & Transplantat, Paris, France
[11] Dept Nephrol Transplantat & Dialysis, Bordeaux, France
[12] Univ Hosp, Dept Nephrol, Amiens, France
[13] Univ Hosp, Dept Nephrol & Clin Immunol, Tours, France
[14] Univ Hosp, Dept Nephrol, Dijon, France
[15] St Louis Hosp, Dept Nephrol & Transplantat, Paris, France
[16] Univ Hosp, Dept Nephrol & Dialysis, Nancy, France
[17] Hop Xavier Bichat, Dept Nephrol, Paris, France
[18] Roche SAS, Neuilly Sur Seine, France
[19] Univ Hosp, Dept Nephrol Dialysis & Organ Transplantat, Toulouse, France
关键词
Early corticosteroid withdrawal; Kidney transplantation; Mycophenolate mofetil; Therapeutic drug monitoring; SUBCLINICAL REJECTION; FREE IMMUNOSUPPRESSION; RENAL-TRANSPLANTATION; PROTOCOL BIOPSIES; RISK-FACTORS; MULTICENTER; STANDARD; PHARMACOKINETICS; METAANALYSIS; BASILIXIMAB;
D O I
10.1097/TP.0b013e318234e134
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Early posttransplant steroid withdrawal may increase the risk of acute rejection and the occurrence of subclinical acute rejection (SCAR). We assessed the feasibility and safety of early steroid withdrawal in low-risk patients receiving cyclosporine A (CsA) and the impact of optimization of mycophenolic acid exposure on steroid withdrawal success. Methods. De novo, low-immunological risk kidney recipients received an anti-interleukin-2-receptor-alpha antibody induction, a short course of 7 days of corticosteroids, and CsA with 2-hr postdose concentration monitoring. They were randomized to adjusted dose (AD) of mycophenolate mofetil (MMF) using therapeutic drug monitoring (TDM) or a fixed-dose (FD) regimen. MMF 3 g was initiated posttransplant and then adjusted starting at week 2 to a 0 to 12 hr area under the concentration time curve of 40 mg . h/L versus 2 g daily, respectively. The primary endpoint was a composite of the proportion of patients experiencing biopsy-proven acute rejection (BPAR) and those with SCAR identified on the 3-month protocol biopsy. Results. Among 247 analyzed patients, only 22 in the AD group and 17 in the FD group experienced BPAR or SCAR (P = 0.46). The rate of SCAR was low: 4% (AD) and 2.5% (FD). No between-group difference in the incidence of BPAR was observed. TDM yielded MMF doses ranging from 1 to 4 g/d and significantly reduced interpatient variability at weeks 26 and 52 in the AD group. Conclusions. In low-immunological risk kidney recipients, MMF combined with CsA allows early corticosteroid discontinuation with good tolerability. In this group of patients, TDM of MMF does not improve clinical outcome.
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收藏
页码:1244 / 1251
页数:8
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