Benefit of early conversion from CNI-based to everolimus-based immunosuppression in heart transplantation.

BACKGROUND

Calcineurin inhibitor (CNI)-induced nephrotoxicity is a feared adverse effect after heart transplantation (HTx). In patients with advanced renal failure we performed an overnight conversion from cyclosporine (CsA) to everolimus within the first year after HTx and compared changes in renal function to a similar switch performed in a group of long-term HTx survivors with 24-month follow up.

METHODS

Sixteen HTx recipients (Group 1), including 5 patients undergoing dialysis, were switched overnight from CsA to everolimus at 5.5 (range 1.3 to 8.5) months post-operatively, whereas 15 patients completed 24 months of follow-up. Fifteen long-term survivors (Group 2) were recruited at 96 (58 to 148) months post-HTx. Due to 3 withdrawals and 2 deaths, 10 of these 15 patients remained available for follow-up assessment.

RESULTS

In Group 1 patients, creatinine level improved from 211 (186 to 263) to 112 (98 to 140) mumol/liter and estimated glomerular filtration rate (eGFR) from 29 (20 to 35) to 62 (43 to 69) ml/min/1.73 m(2) (p < 0.001). In Group 2, creatinine decreased from 227 (188 to 255) to 193 (150 to 250) micromol/liter (p = 0.299), and eGFR increased from 26 (21 to 31) to 28 (22 to 35) ml/min/1.73 m(2) (p = 0.225). Four cellular rejections were treated successfully in Group 1. All together, 24 adverse events occurred.

CONCLUSIONS

These preliminary data are the first to suggest that the improvement in renal function after switching to CNI-free everolimus treatment has the greatest potential within the first year post-HTx. While we await randomized, controlled trials, it appears that conversion can be performed with acceptable safety in selected patients.