Everolimus allows early CNI-reduction and late withdrawal in heart transplant recipients resulting in improved renal function

Objectives: Nephrotoxicity is a common side effect of immunosuppressive protocols based on calcineurin-inhibitors (CNI). M-TOR-inhibitors like sirolimus have proven to be efficacious in preventing renal failure after heart transplantation (HTx). The combination everolimus (EVL)/tacrolimus (Tac) as well as CNI-free immunosuppression with EVL has not been investigated after HTx. We evaluated the impact of CNI-reduction and withdrawal in EVL-based immunosuppression on renal function after HTx. Methods: Between 2007 and 2010, 22 patients (19 male, mean age 53.5±17.3 years) were switched from Tac and mycophenolate mofetil (MMF) to an EVL-based immunosuppression for renal dysfunction. Patients were divided into two groups: patients within one year after HTx were switched to Tac/EVL (group 1, n=11) and patients longer than one year after HTx to EVL/MMF (group 2, n=11). Target trough levels were 3–5ng/mL for Tac, 1.5–4µg/mL for MMF, and 4–10ng/mL for EVL. Creatinine levels were measured up to six months after conversion. Results: Renal function improved in all patients: baseline creatinine was 2.4±0.8mg/dl, 2.0±0.9mg/dl (p=0.10) three months and 1.8±0.7mg/dl six months after conversion (p=0.04). In group 1 baseline creatinine was 2.2±0.7mg/dl, 1.8±0.7mg/dl three months and 1.6±0.5mg/dl six months after conversion. In group 2 baseline creatinine was 2.7±0.9mg/dl, 2.2±1.2mg/dl three months and 2.1±0.9mg/dl after six months. There were no acute rejection episodes. Due to adverse events (anaemia, pneumonia, edema) seven patients (31.8%) were re-converted to the CNI-based immunosuppression. Conclusions: EVL allows early CNI-reduction and late withdrawal after HTx resulting in improved renal function. Side effects are common and lead to a high reconversion rate.