title: Sirolimus Immunoprophylaxis and Renal Histological Changes in Long-Term Cardiac Transplant Recipients: A Pilot Study.
abstract: The effects of sirolimus (SIR), as a substitution for calcineurin inhibitor (CNI) immunoprophylaxis, on renal function in very-long-term cardiac transplant recipients have been a matter of controversy.
  
  
  
  To assess the impacts of SIR as a substitution for CNI on renal function up to 24 months in long-term cardiac recipients as well as the renal histological changes in patients with suspected CNI-induced nephrotoxicity.
  
  
  
  A total of 23 cardiac transplant recipients aged 57.7 ± 11.2 years, 91 months post-cardiac transplantation were recruited; 15 patients were randomized to CNI-free immune suppression with SIR, and 8 patients were allocated to continue their CNI regimens. Serum creatinine and calculated serum creatinine clearance were measured at prespecified time points up to 24 months. Renal structure and function were assessed by renal biopsies, renal ultrasound, and magnetic resonance imaging at baseline.
  
  
  
  There were no significant changes in creatinine clearance during the course of the study in patients treated with SIR. However, SIR-treated patients exhibited a significant decrease in 24-hours and nighttime systolic and diastolic blood pressures. Typical findings of significant hypertensive renal disease were detected in 9 of the 11 (82%) patients. Features of chronic CNI toxicity were detected in 6 (55%) patients.
  
  
  
  There is a very high rate of hypertensive renal disease concomitantly with some degree of CNI toxicity in long-term cardiac transplant recipients with renal dysfunction. This very high rate of hypertension-related disease may limit the impact of SIR on improving renal function long term following cardiac transplantation.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Canada m_white@icm-mhi.com.
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.affiliation: Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Boucher
authors.affiliation: Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Canada.
authors.forename: Raymond
authors.initials: R
authors.lastname: Dandavino
authors.affiliation: Montréal Heart Institute Coordinating Center, Montréal, Canada.
authors.forename: Annik
authors.initials: A
authors.lastname: Fortier
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Canada.
authors.forename: Guy B
authors.initials: GB
authors.lastname: Pelletier
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Canada.
authors.forename: Normand
authors.initials: N
authors.lastname: Racine
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Canada.
authors.forename: Anique
authors.initials: A
authors.lastname: Ducharme
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: de Denus
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montréal, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Carrier
authors.affiliation: Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Canada.
authors.forename: Suzon
authors.initials: S
authors.lastname: Collette
keywords: calcineurin inhibitors; cardiac transplantation; renal function; sirolimus