Avoidance of calcineurin inhibitors with use of proliferation signal inhibitors in de novo heart transplantation with renal failure

Abstract

Background: This study describes our experience with proliferation signal inhibitors in de novo heart transplant recipients with significant renal impairment. To circumvent further nephrotoxicity, calcineurin inhibitors were avoided in the peri-operative period.

Methods: Immunosuppression in 20 patients was with a proliferation signal inhibitor (sirolimus, 14; everolimus, 6), an anti-mitotic drug, and corticosteroids from the time of transplantation. Induction was used in 9 patients (45%). All patients had preoperative significant renal dysfunction (mean glomerular filtration rate <30 ml/min/1.73 m(2)), and 4 patients required dialysis.

Results: Post-operatively, the glomerular filtration rate significantly increased (>65 ml/min/1.73 m(2) at Month 1, remaining stable thereafter). No patients required dialysis after the first month of transplantation. Mean follow-up was 500 days. Rejection episodes occurred in 11 patients (55%), and 4 patients died (2 of rejection, although 1 death occurred 48 days after conversion to conventional treatment with tacrolimus). Half of the patients were eventually converted to conventional calcineurin-inhibitor therapy because of proliferation signal inhibitor adverse events.

Conclusion: Although this immunosuppressive approach was associated with a somewhat high rate of rejection and frequent side effects, it represents an attractive alternative in the complicated peri-operative setting of patients with significant renal impairment. This approach could serve as a temporary bridge to a conventional treatment.