Careggi University Hospital– Cyclosporine “very low exposure” with Everolimus “high exposure” is associated with better outcomes in renal transplant patients with respect to standard treatment with EC-MPS Elisabetta Bertoni, Giuseppina Rosso, Aida Larti, Lorenzo Di Maria, Maria Zanazzi, Maurizio Salvadori RENAL UNIT Careggi University Hospital– Florence ,Italy

AIM OF THE STUDY PATIENTS AND METHODS Aim of the study was to compare in cadaveric renal transplant recipients the efficacy of CyA “very low exposure” with Everolimus “high exposure” with respect to CyA “standard exposure” with EC-MPS PATIENTS AND METHODS In a randomized, prospective, monocenter, open study, 106 patients were enrolled to receive : 56 pts : Everolimus (to reach C0 8-10 ng/ml) + CyA (to reach C2 250-300 ng/ml ) + steroids 50 pts : EC-MPS (1440 mg/day) + Cya (to reach C2 500-700 ng/ml) + steroids - Efficacy was evaluated at 24 months - Data analyses have been made per protocol Efficacy was evaluated at 3 and 12 months. Data analyses have been made per protocol

PATIENTS CHARACTERISTICS EC-MPS Standard CyA exposure Everolimus Very low exposure CyA p Number 50 56 Recipient age (years) 49.75 ± 12.06 45.70 ± 12.77 NS Donor age (years) 50.23 ± 16.26 47.40 ± 15.91 Dialysis Duration (months) 43.23 ± 36.1 42.02 ± 31.5 Cold Ischemia Time (hours) 19.80 ± 5.01 18.30 ± 3.67 Mismatches 3.5 ± 1.3 3.364 ± 1.06

First period hospitalization (days) RESULTS I EC-MPS Standard CyA exposure Everolimus Very low exposure CyA p First period hospitalization (days) 24.57 ± 12.20 24.77 ± 11.13 NS BPAR 24% 18.8% CMV infection 27% 26%

RESULTS II 2-YEAR GRAFT SURVIVAL p = ns

RESULTS III CyA dose at 2 years 2.30.64 P < 0.0001 1.350.49

RESULTS IV eGFR (Cockcroft-Gault) at 2 years p < 0.001 77.78±31.9 54.76±18.76

RESULTS V Systolic blood pressure at 2 years p = NS 129.8±16.23 125.3±13.96

RESULTS VII Serum cholesterol at 2 years p < 0.01 229.747.08 206.742.2 RR =1.72

Such therapy was associated with CONCLUSIONS Everolimus high exposure associated with very low CyA exposure compared with EC-MPS associated with standard CyA exposure was safe and effective Such therapy was associated with Lower incidence of acute rejection and higher 2-year graft survival Significant higher eGFR at 2 years Significant higher serum cholesterol levels in E patients at 2 years 24 hours proteinuria was low and similar in both groups

BPAR rate at 2 years P = NS 11