title: Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial.
abstract: BACKGROUND
  Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes.
  
  
  METHODS
  In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 < trough CsA concentrations <200 μg/L, n = 47) or a standard dose of Cyclosporine A (200 < trough CsA concentrations <300 μg/L, n = 48) for the three first post-transplant months along with mycophenolate mofetil and corticosteroids. Participants had a stable haemodynamic status, a serum creatinine level <250 μmol/L and the donors' cold ischemia time was under six hours; multiorgan transplants were excluded. The change in serum creatinine level over 12 months was used as the main criterion for renal function. Intention-to-treat analysis was performed on the 95 randomised patients and a mixed generalised linear model of covariance was applied.
  
  
  RESULTS
  At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis.
  
  
  CONCLUSIONS
  In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00159159.
authors.affiliation: Hospices Civils de Lyon, Hôpital Louis Pradel, Pôle Médico-Chirurgical de Transplantation Cardiaque Adulte, Bron Cedex, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Boissonnat
authors.forename: Ségolène
authors.initials: S
authors.lastname: Gaillard
authors.forename: Catherine
authors.initials: C
authors.lastname: Mercier
authors.forename: Michel
authors.initials: M
authors.lastname: Redonnet
authors.forename: Bernard
authors.initials: B
authors.lastname: Lelong
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Mattei
authors.forename: Annick
authors.initials: A
authors.lastname: Mouly-Bandini
authors.forename: Sabine
authors.initials: S
authors.lastname: Pattier
authors.forename: Agnès
authors.initials: A
authors.lastname: Sirinelli
authors.forename: Eric
authors.initials: E
authors.lastname: Epailly
authors.forename: Shaida
authors.initials: S
authors.lastname: Varnous
authors.forename: Marc-Alain
authors.initials: MA
authors.lastname: Billes
authors.forename: Laurent
authors.initials: L
authors.lastname: Sebbag
authors.forename: René
authors.initials: R
authors.lastname: Ecochard
authors.forename: Catherine
authors.initials: C
authors.lastname: Cornu
authors.forename: François
authors.initials: F
authors.lastname: Gueyffier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine