This prospective study evaluated 24 renal transplant patients who were stable under an immunosuppressive regimen consisting of cyclosporine, corticosteroids, and mycophenolate, but in need of CNI-free drug regimen due to signs and symptoms of CNI induced toxicity, per clinical judgment. Patients were converted from CSA to EVR therapy in association with mycophenolate sodium (720 mg/ day BID) and prednisone. A complete PK study for everolimus was performed 30 days after conversion and patients were followed for 5 years. Results: The mean age of this population was 41.6 ± 8.61 years, 62.5% male sex and 66.7% Caucasian ethnicity. Mean transplantation time at conversion was 60.8 ± 33.7 months and mean seric creatinine was 1.8 ± 0.5 mg/dL. The initial EVR dose was 2.0 mg/day for the first 7 patients and 4.0 mg/day for 17 patients. After 30 days, the following pharmacokinetic dose-adjusted parameters were calculated: C0=2.7±1.2 ng/mL/mg, Cmax 12.0±3.5 ng/mL/mg, Cmin 2.53±1.2 ng/mL/mg, Tmax=0.8±0.3 h and AUC(0-12)=59.2±23.2 Μg*h/L/mg. Over 5-years of follow up, this regimen resulted in a number of adverse events: (81,4% infections, 7% cardiovascular and 11,6% gastrointestinal disorders). 24% of the patients discontinued EVR (50% proteinuria, 33% infection and 27% dyslipidemia). After 5 years of follow-up, patients who had a higher 30-day AUC (above 83.8 Μg*h/L) and mean trough blood concentration (above 9 ng/mL) during follow-up period showed higher incidence of everolimus-associated adverse reactions (mainly dyslipidemia and hypertriglyceridemia) and higher rates of EVR discontinuation (66.7 %). Two patients (8.3%) experienced late biopsy proven acute rejection. The mean seric creatinine after 5 years of conversion was 2.17±1.02 mg/dL. Patient, graft and death censored graft survival rates were 96%, 79% and 83%, respectively and the EVR discontinuation-free survival was 74%. Conclusion: In a selected kidney transplant population, conversion from CsA to EVR was associated with stable renal function over 5-years of follow up. The adverse event profile and the discontinuation rate were associated with higher EVR exposure 30 days after conversion.

Tedesco, H.: Grant/Research Support, Everolimus.

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