Calcineurin inhibitor-free mycophenolate mofetil/sirolimus maintenance in liver transplantation: the randomized spare-the-nephron trial

Lewis Teperman, Dilip Moonka, Anthony Sebastian, Linda Sher, Paul Marotta, Christopher Marsh, Baburao Koneru, John Goss, Dennis Preston, John P Roberts, Spare-the-Nephron Trial Liver Transplantation Study Group

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Mycophenolate mofetil (MMF) and sirolimus (SRL) have been used for calcineurin inhibitor (CNI) minimization to reduce nephrotoxicity following liver transplantation. In this prospective, open-label, multicenter study, patients undergoing transplantation from July 2005 to June 2007 who were maintained on MMF/CNI were randomized 4 to 12 weeks after transplantation to receive MMF/SRL (n = 148) or continue MMF/CNI (n = 145) and included in the intent-to-treat population. The primary efficacy endpoints were the mean percentage change in the calculated glomerular filtration rate (GFR) and a composite of biopsy-proven acute rejection (BPAR), graft lost, death, and lost to follow-up 12 months after transplantation. Patients were followed for a median of 519 days after randomization. MMF/SRL was associated with a significantly greater renal function improvement from baseline with a mean percentage change in GFR of 19.7 ± 40.6 (versus 1.2 ± 39.9 for MMF/CNI, P = 0.0012). The composite endpoint demonstrated the noninferiority of MMF/SRL versus MMF/CNI (16.4% versus 15.4%, 90% confidence interval = -7.1% to 9.0%). The incidence of BPAR was significantly greater with MMF/SRL (12.2%) versus MMF/CNI (4.1%, P = 0.02). Graft loss (including death) occurred in 3.4% of the MMF/SRL-treated patients and in 8.3% of the MMF/CNI-treated patients (P = 0.04). Malignancy-related deaths were less frequent with MMF/SRL. Adverse events caused withdrawal for 34.2% of the MMF/SRL-treated patients and for 24.1% of the MMF/CNI-treated patients (P = 0.06). The use of MMF/SRL is an option for liver transplant recipients who can benefit from improved renal function but is associated with an increased risk of rejection (but not graft loss).

Original languageEnglish (US)
Pages (from-to)675-89
Number of pages15
JournalLiver Transplantation
Volume19
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • Adult
  • Aged
  • Biopsy
  • Calcineurin Inhibitors
  • Drug Administration Schedule
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Immunosuppression
  • Immunosuppressive Agents
  • Incidence
  • Kidney Diseases
  • Liver Transplantation
  • Male
  • Middle Aged
  • Mycophenolic Acid
  • Nephrons
  • Prospective Studies
  • Reproducibility of Results
  • Sirolimus
  • Time Factors
  • Treatment Outcome
  • Young Adult
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

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