title: Renal function to 5 years after late conversion of kidney transplant patients to everolimus: a randomized trial.
abstract: BACKGROUND
  Few trials have investigated late preemptive conversion of kidney transplant patients from a calcineurin inhibitor (CNI) to an mTOR inhibitor.
  
  
  METHODS
  In an open-label, 12-month, prospective, randomized, parallel-group study, maintenance kidney transplant patients (>6 months post-transplant) either switched from CNI to everolimus or continued their current CNI regimen. Patients who completed the core study were followed to 5 years post-randomization.
  
  
  RESULTS
  Of 93 randomized patients, 78 completed the core study and 67 attended the final 60-month study visit. Mean time post-transplant at baseline was 82.6 months and 70.5 months in the everolimus and CNI groups, respectively. At month 60, adjusted mean eGFR (Nankivell) was 63.0 (95% CI 57.8, 68.2) mL/min/1.73 m(2) in the everolimus group versus 57.9 (95% CI 52.6, 63.1) mL/min/1.73 m(2) in the CNI group, a difference of 5.1 (95% CI -0.6, 10.8) mL/min/1.73 m(2) (p = 0.076). Among patients who remained on randomized study drug at month 60, mean eGFR (Nankivell) was 71.6 (95% CI 64.2, 79.0) mL/min/1.73 m(2) in everolimus-treated patients (n = 21) versus 60.6 (95% CI 55.1, 66.1) mL/min/1.73 m(2) in CNI-treated patients (n = 29) (mean difference 11.0; 95% CI 3.6, 18.5 mL/min/1.73 m(2); p = 0.005). No cases of BPAR occurred from randomization to month 60 in either group. Graft loss occurred in three everolimus-treated patients and one CNI-treated patient. No unexpected safety concerns were observed in either group.
  
  
  CONCLUSIONS
  Late preemptive conversion of maintenance kidney transplant patients from CNI to everolimus may be associated with improved long-term renal function and preserves immunosuppressive efficacy. Patient numbers were low, but these findings merit further investigation.
authors.affiliation: Department of Nephrology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommerer
authors.forename: Thomas
authors.initials: T
authors.lastname: Rath
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Barbara
authors.initials: B
authors.lastname: Suwelack
authors.forename: Daniel
authors.initials: D
authors.lastname: Baeumer
authors.forename: Christian
authors.initials: C
authors.lastname: Sieder
authors.forename: Martina
authors.initials: M
authors.lastname: Porstner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Arns
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D057915:Drug Substitution; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006084:Graft Rejection / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases