title: Renal, efficacy and safety outcomes following late conversion of kidney transplant patients from calcineurin inhibitor therapy to everolimus: the randomized APOLLO study.
abstract: OBJECTIVE
  The primary objective of this trial was to demonstrate, based on the estimated glomerular filtration rate (eGFR), superior renal function at month 12 after conversion of maintenance kidney transplant patients from calcineurin inhibitor (CNI) therapy to everolimus, compared to continuing a standard CNI regimen.
  
  
  METHODS
  APOLLO was an open-label, 12-month, prospective, multicenter study in which 93 maintenance kidney transplant patients were randomized to convert from CNI to everolimus (n = 46) or remain on standard CNI-based immunosuppression (n = 47). The primary efficacy variable was eGFR (Nankivell formula) 12 months after randomization. The study was terminated prematurely due to slow recruitment and was thus underpowered.
  
  
  RESULTS
  Mean time post-transplant was 83.5 months with everolimus and 70.1 months with CNI. Adjusted values for eGFR (Nankivell) at month 12 were 61.6 (95% CI 58.1, 65.1) mL/ min/1.73 m² with everolimus and 58.8 (95% CI 55.2, 62.3) mL/min/1.73 m² with CNI, a difference of 2.8 (95% CI -1.0, 6.7) mL/ min/1.73 m² (p = 0.145) i.e., the primary objective was not met. Using the modification of diet in renal disease (MDRD) formula, adjusted eGFR at month 12 was significantly higher with everolimus (p = 0.030). In the subpopulation who remained on the study drug (n = 52), the difference in the adjusted change from randomization was 6.6 (95% CI 1.5, 11.6) mL/min/1.73 m² (p = 0.013) in favor of everolimus. There was no biopsyproven acute rejection and no graft losses. Adverse events led to discontinuation of everolimus and CNI in 32.6% and 10.6% of patients, respectively.
  
  
  CONCLUSIONS
  Conversion from CNI to everolimus to preserve renal function can be considered several years after kidney transplantation and does not compromise immunosuppressive efficacy.
authors.affiliation: Department of Nephrology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Department of Nephrology and Transplantation Medicine, Westpfalz- Klinikum, Kaiserslautern, Department of Nephrology, Heidelberg University Hospital, Heidelberg, Department of Nephrology and Hypertensiology, Hannover Medical School, Hannover, Department of Transplantation, Division of Internal Medicine and Nephrology, Charité Universitätsmedizin Berlin, Campus Virchow, Berlin, Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Department of Internal Medicine D, Transplant Nephrology, University of Münster, Münster, Novartis Pharma GmbH, Nuernberg, Department of Nephrology, Medical Clinic Köln-Merheim, Cologne, Germany, and APOLLO Study Group.
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Thomas
authors.initials: T
authors.lastname: Rath
authors.forename: Claudia
authors.initials: C
authors.lastname: Sommerer
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
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: Christoph
authors.initials: C
authors.lastname: May
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*; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000502:physiology / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus