Introduction: The aim of the study was to compare efficacy of cyclosporine (CsA) very low exposure with everolimus high exposure, with respect to CsA standard exposure with enteric-coated mycophenolate sodium (EC-MPS) therapy.
Methods: In a randomized, prospective, single-center, open-label study, patients were enrolled to receive either everolimus (C0 (trough level) 8-12 ng/mL) + CsA (C2 (CsA level 2 hours after drug administration) 250-300 ng/mL) + steroids, or EC-MPS (1,440 mg/day) + CsA (C2 500-700 ng/mL) + steroids. Fifty-six patients were enrolled in the everolimus group, 50 in the EC-MPS group. Efficacy was evaluated at 3 and 12 months.
Results: Characteristics of groups were similar. Biopsy-proven acute rejection (BPAR) rates were similar in both groups (everolimus 18.8% vs. EC-MPS 18.2%). Everolimus patients had a lower incidence of delayed graft function (DGF) than EC-MPS patients (22.6% vs. 40.9%; p<0.05; relative risk [RR] = 0.65). One-year graft survival was 95% in the everolimus group and 88% in the EC-MPS group (p=NS). CsA dose at 1 year was lower in the everolimus group (1.52 ± 0.67 vs. 2.55 ± 0.79 mg/kg; p<0.0001). Estimated glomerular filtration rate (eGFR; Cockcroft-Gault) was higher in the everolimus group (81.64 ± 32.67 vs. 62.62 ± 22.81 ml/min; p<0.001). Systolic blood pressure was lower in the everolimus group (124.9 ± 14.64 mm Hg vs. 131.1 ± 13.23 mm Hg; p=0.03). Hemoglobin blood levels were slightly lower in the everolimus group (12.62 ± 1.42 vs. 13.01 ± 1.3 g/L; p=NS; for anemia, RR=1.302). Serum cholesterol was similar in both groups (everolimus 219.1 ± 47.20 vs. EC-MPS 207.2 ± 38.8 mg/dL; p=NS), but everolimus patients used more statins (RR=1.49). Twenty-four-hour proteinuria was higher in the everolimus group (519.7 ± 77.31 vs. 296.7 ± 33.42 mg/24 hours; p=0.01).
Conclusions: Everolimus regimen compared with EC-MPS regimen is associated with lower incidence of DGF, slightly better 1-year graft survival rate, a significantly higher GFR and lower systolic blood pressure.