title: Freedom from rejection and stable kidney function are excellent criteria for steroid withdrawal in tacrolimus-treated kidney transplant recipients.
abstract: OBJECTIVE
  This prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids.
  
  
  METHODS
  In total 489 patients were randomised to receive either tacrolimus and MMF (n = 243) or tacrolimus and azathioprine (n = 246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg/kg/day, MMF dose was 1 g/day, azathioprine was administered at 1-2 mg/day. Steroids were tapered from 20 mg/day to 5 mg/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol/L. Study duration was 6 months.
  
  
  RESULTS
  Patient survival at month 6 was 98.3% (Tac/MMF/S) and 98.4% (Tac/Aza/S), graft survival at 6 month was 95.0% (Tac/MMF/S) and 93.5% (Tac/Aza/S). The 6-month incidences of biopsy-proven acute rejection were 18.9% (Tac/MMF/S) compared with 26.8% (Tac/Aza/S), p = 0.038. The 6-month incidences of steroid-resistant acute rejection were 2.1% (Tac/MMF/S) and 4.9% (Tac/Aza/S), p = ns. At the end of month 3, steroid withdrawal was performed in 60.5% (Tac/MMF/S) and 48.8% (Tac/Aza/S) of patients, p < 0.01. During months 4-6, 2.7% of patients in the Tac/MMF group had a biopsy-confirmed acute rejection compared with 0.8% of patients in the Tac/Aza group. In patients who continued to receive steroids, the incidences of biopsy-proven acute rejections during months 4-6 were 3.5% (Tac/MMF/S) and 7.1% (Tac/Aza/S). At study end, the steroid-free patients had an excellent kidney function, the median serum creatinine concentration was 119.5 mumol/L (Tac/MMF) and 115.1 mumol/L (Tac/Aza); the median serum creatinine of the total study group was 130.5 mumol/L (Tac/MMF/S) and 132.8 mumol/L (Tac/Aza/S).
  
  
  CONCLUSIONS
  Both tacrolimus regimens are efficacious and safe. The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients. The overall incidence of acute rejection was low and kidney function was good.
authors.affiliation: Department of Transplantology, Poznan District Hospital, Poznan, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Włodarczyk
authors.forename: J
authors.initials: J
authors.lastname: Wałaszewski
authors.forename: F
authors.initials: F
authors.lastname: Perner
authors.forename: S
authors.initials: S
authors.lastname: Vitko
authors.forename: M
authors.initials: M
authors.lastname: Ostrowski
authors.forename: P
authors.initials: P
authors.lastname: Bachleda
authors.forename: F
authors.initials: F
authors.lastname: Kokot
authors.forename: M
authors.initials: M
authors.lastname: Klinger
authors.forename: P
authors.initials: P
authors.lastname: Szenohradsky
authors.forename: P
authors.initials: P
authors.lastname: Studenik
authors.forename: P
authors.initials: P
authors.lastname: Navratil
authors.forename: L
authors.initials: L
authors.lastname: Asztalos
authors.forename: B
authors.initials: B
authors.lastname: Rutkowski
authors.forename: K Kalmar
authors.initials: KK
authors.lastname: Nagy
authors.forename: D
authors.initials: D
authors.lastname: Hickey
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011183:Postoperative Complications / Q000145:classification / Q000453:epidemiology / Q000517:prevention & control; D012086:Reoperation; D013256:Steroids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D014019:Tissue Donors / Q000706:statistics & numerical data
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus