title: Calcineurin inhibitor-free mycophenolate mofetil/sirolimus maintenance in liver transplantation: the randomized spare-the-nephron trial.
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).
authors.affiliation: Mary Lea Johnson Richards Organ Transplant Center, New York University School of Medicine, New York, NY 10016, USA. lewis.teperman@med.nyu.edu
authors.forename: Lewis
authors.initials: L
authors.lastname: Teperman
authors.forename: Dilip
authors.initials: D
authors.lastname: Moonka
authors.forename: Anthony
authors.initials: A
authors.lastname: Sebastian
authors.forename: Linda
authors.initials: L
authors.lastname: Sher
authors.forename: Paul
authors.initials: P
authors.lastname: Marotta
authors.forename: Christopher
authors.initials: C
authors.lastname: Marsh
authors.forename: Baburao
authors.initials: B
authors.lastname: Koneru
authors.forename: John
authors.initials: J
authors.lastname: Goss
authors.forename: Dennis
authors.initials: D
authors.lastname: Preston
authors.forename: John P
authors.initials: JP
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D065095:Calcineurin Inhibitors; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D007674:Kidney Diseases / Q000150:complications / Q000517:prevention & control*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009399:Nephrons / Q000601:surgery*; D011446:Prospective Studies; D015203:Reproducibility of Results; D020123:Sirolimus / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus