title: Early steroid withdrawal and optimization of mycophenolic acid exposure in kidney transplant recipients receiving mycophenolate mofetil.
abstract: 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-α 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.
authors: Department of Nephrology, University Hospital, Brest, France. yannick.lemeur@chu-brest.fr
authors: Yannick
authors: Y
authors: Le Meur
authors: Antoine
authors: A
authors: Thierry
authors: François
authors: F
authors: Glowacki
authors: Jean-Philippe
authors: JP
authors: Rerolle
authors: Valerie
authors: V
authors: Garrigue
authors: Nacera
authors: N
authors: Ouali
authors: Anne-Elisabeth
authors: AE
authors: Heng
authors: Michel
authors: M
authors: Delahousse
authors: Laeticia
authors: L
authors: Albano
authors: Philippe
authors: P
authors: Lang
authors: Lionel
authors: L
authors: Couzi
authors: Maite
authors: M
authors: Jaureguy
authors: Yvon
authors: Y
authors: Lebranchu
authors: Christiane
authors: C
authors: Mousson
authors: Denis
authors: D
authors: Glotz
authors: Michele
authors: M
authors: Kessler
authors: François
authors: F
authors: Vrtovsnik
authors: Stephanie
authors: S
authors: Rouanet
authors: Nailya
authors: N
authors: Tagieva
authors: Nassim
authors: N
authors: Kamar
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid