Does everolimus associated with a low dose of cyclosporine in long-term cardiac transplant recipients improve renal function? Initial experience

Cyclosporine (CsA) renal toxicity is a well-known side effect. Various immunosuppressive strategies have been developed to minimize renal insufficiency. The use of everolimus associated with low levels of CsA can be an alternative strategy.

From October 2007 to April 2008, everolimus was started with a lower dose of cyclosporine (trough levels from 109.3 +/- 27.5 to 93.7 +/- 30.1 ng/mL after 45 days) in 21 cardiac transplant recipients (18 male and 3 female patients, mean age 56.4 +/- 10.7 years). Pre-everolimus therapy creatinine levels, creatinine clearances, and glomerular filtration rates were 1.9 +/- 0.9 mg/dL, 54.2 +/- 18.1 mL/mins and 44.3 +/- 16.5 mL/min/m(2), respectively.

We observed a significant reduction in creatinine levels (from 1.9 +/- 0.9 to 1.4 +/- 0.3 mg/dL, P = .022) as well as a significant improvement in creatinine clearances (from 54.2 +/- 18.1 to 69.0 +/- 19.0 mL/min, P = .020) and glomerular filtration rates (from 44.3 +/- 16.5 to 57.1 +/- 16.3 mL/min/m(2), P = .010) after 7 days of everolimus therapy. Upon univariate analysis patient age, pretransplantation creatinine clearance, creatinine clearance after everolimus introduction, glomerular filtration rate at 45 days, and time from transplantation were associated with renal improvement. Upon multivariate analysis, only creatinine clearance at 7 days was related to the renal improvement.

These preliminary data suggested that everolimus with a low dose of CsA may be safe and effective to reduce CsA-related renal insufficiency among selected, heart transplant patients.