title: Impact of the reduction of calcineurin inhibitors on renal function in heart transplant patients: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Calcineurin inhibitors (CNIs) taken after heart transplantation lead to excellent short-term outcomes, but long-term use may cause chronic nephrotoxicity. Our aim was to identify, appraise, select and analyse all high-quality research evidence relevant to the question of the clinical impact of CNI-sparing strategies in heart transplant patients.
  
  
  METHODS
  We carried out a systematic review and meta-analysis of randomized controlled trials on CNI reduction in heart transplant recipients. Primary outcomes were kidney function and acute rejection after 1 year. Secondary outcomes included graft loss, all-cause mortality and adverse events.
  
  
  RESULTS
  Eight open-label studies were included, with 723 patients (four tested de novo CNI reduction and four maintenance CNI reduction). Calcineurin inhibitor reduction did not improve creatinine clearance at 12 months 5.46 [-1.17, 12.03] P = 0.32 I(2)  = 65.4%. Acute rejection at 12 months (55/360 vs. 52/332), mortality (18/301 vs. 15/270) and adverse event rates (55/294 vs. 52/281) did not differ between the low-CNI and standard-CNI groups. There was significant benefit on creatinine clearance in patients with impaired renal function at 6 months [+12.23 (+5.26, +18.82) ml min(-1) , P = 0.0003] and at 12 months 4.63 [-4.55, 13.82] P = 0.32 I(2)  = 75%.
  
  
  CONCLUSIONS
  This meta-analysis did not demonstrate a favourable effect of CNI reduction on kidney function, but there was no increase in acute rejection. To provide a better analysis of the influence of CNI reduction patterns and associated treatments, a meta-analysis of individual patient data should be performed.
authors.affiliation: INSERM, CIC201, Lyon, France; CHU Lyon, Service de Pharmacologie Clinique, Lyon, France; Université de Lyon, UMR 5558, Lyon, France; Hospices Civils de Lyon, Hôpital Louis Pradel, Bron Cedex, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cornu
authors.forename: Christophe
authors.initials: C
authors.lastname: Dufays
authors.forename: Ségolène
authors.initials: S
authors.lastname: Gaillard
authors.forename: François
authors.initials: F
authors.lastname: Gueyffier
authors.forename: Michel
authors.initials: M
authors.lastname: Redonnet
authors.forename: Laurent
authors.initials: L
authors.lastname: Sebbag
authors.forename: Ana
authors.initials: A
authors.lastname: Roussoulières
authors.forename: Christian A
authors.initials: CA
authors.lastname: Gleissner
authors.forename: Jan
authors.initials: J
authors.lastname: Groetzner
authors.forename: Hans B
authors.initials: HB
authors.lastname: Lehmkuhl
authors.forename: Luciano
authors.initials: L
authors.lastname: Potena
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
authors.forename: Pascale
authors.initials: P
authors.lastname: Boissonnat
mesh_terms: D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D002423:Cause of Death; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000139:chemically induced* / Q000453:epidemiology; D016027:Heart Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology*; D011183:Postoperative Complications / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic
chemical_list: D065095:Calcineurin Inhibitors; D003404:Creatinine
keywords: calcineurin inhibitor; heart transplantation; meta-analysis; renal function