title: Conversion from everolimus with low-exposure cyclosporine to everolimus with mycophenolate sodium maintenance therapy in kidney transplant recipients: a randomized, open-label multicenter study.
abstract: BACKGROUND
  Data in kidney transplant recipients regarding elimination of calcineurin inhibitor (CNI) therapy from a de novo regimen based on low CNI exposure and an mTOR inhibitor are sparse, and restricted to CNI elimination within the first six months post-transplant.
  
  
  METHODS
  In a 12-month, randomized, multicenter, open-label study, kidney transplant patients who had received everolimus, low-exposure cyclosporine and corticosteroids from transplantation to month 12 (with proteinuria <1 g/24 h at month 12) were randomized to convert from cyclosporine to mycophenolate sodium 720 mg/day with increased everolimus exposure (6-10 ng/mL [CNI-free group], n=15) or continue unchanged (everolimus 3-8 ng/mL [CNI group], n=15).
  
  
  RESULTS
  Median (range) baseline mGFR was 54 (21-87) mL/min and 37 (range 18-69) mL/min (p=0.053) in the CNI-free and CNI groups, respectively, compared to 56 (18-126) mL/min and 32 (12-63) mL/min at month 12 (p=0.007). The between-group difference in change in mGFR from baseline to month 12 post-conversion (the primary endpoint) was -14.4 mL/min (95% CI -29.3 to 0.6 mL/min, p=0.059 [least squares mean]). Changes in serum creatinine and estimated GFR to month 12 were significantly in favor of CNI-free patients. One CNI patient experienced biopsy-proven acute rejection. Study drug was discontinued due to adverse events in one CNI-free patient (7%) and three CNI-treated patients (20.0%).
  
  
  CONCLUSIONS
  Elimination of CNI from a de novo regimen of everolimus with low-exposure CNI at one year post-transplant maintained efficacy and led to a non-significant but clinically relevant improvement in renal function, although patients numbers were low (n=30). Findings from this small study require confirmation in a larger controlled trial.
authors.affiliation: Department of Nephrology and Renal Transplantation, Hospital Pasteur, Nice, France. albano.l@chu-nice.fr
authors.forename: Laetitia
authors.initials: L
authors.lastname: Albano
authors.forename: Eric
authors.initials: E
authors.lastname: Alamartine
authors.forename: Olivier
authors.initials: O
authors.lastname: Toupance
authors.forename: Bruno
authors.initials: B
authors.lastname: Moulin
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Rerolle
authors.forename: Rachel
authors.initials: R
authors.lastname: Tetaz
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Moal
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.forename: Stéphane
authors.initials: S
authors.lastname: Quéré
authors.forename: Fabienne
authors.initials: F
authors.lastname: Di Giambattista
authors.forename: Arara
authors.initials: A
authors.lastname: Terpereau
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D005602:France; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D013997:Time Factors
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D009173:Mycophenolic Acid; D020123:Sirolimus