Initial Experience With Sirolimus and Mycophenolate Mofetil for Renal Rescue From Cyclosporine Nephrotoxicity After Heart Transplantation H. Lyster, G. Panicker, N. Leaver, and N.R. Banner ABSTRACT Calcineurin inhibitors (CNIs) have become the cornerstone of immunosuppressive regimens following heart transplantation, but their use is associated with nephrotoxicity. We evaluated a CNI elimination protocol in 14 patients with renal impairment at 48.3  36.0 months after heart transplantation. The mean serum creatinine was 321  107 mol/L; cyclosporine (n = 13) or tacrolimus (n = 1) was discontinued with sirolimus commenced immediately, initially aiming for a target trough level of 16 (12 to 20) ng/mL. If patients were not receiving mycophenolate (MMF) this was initiated at 1 g bid. The transfer period was covered with a tapering course of corticosteroids. In addition to monitoring clinical status, hematology, biochemistry, and sirolimus levels, graft function was assessed by echocardiography, ECG, and, where indicated, endomyocardial biopsy. Renal function improved in 12 patients (with 6 having a greater than 40% decrease in serum creatinine), remained unchanged in 1, and deteriorated in 1. Two patients who were converted at 15 and 139 months after transplantation experienced grade 3A rejection. One patient experienced a fall in ejection fraction without histologic evidence of rejection. Sirolimus was discontinued in three patients because of side effects: bone marrow suppression, presumed lymphocytic pneumonitis, and generalized acneform rash compli- cated by an axillary abcess; 50% of patients continue on sirolimus. In conclusion, withdrawal of CNIs after heart transplantation resulted in an improvement in renal function in most patients: 43% experienced a substantial improvement. CNI elimination protocols need to be refined to reduce the risk of breakthrough rejection and to minimize side effects while protecting renal function after heart transplantation. C ARDIAC transplantation is an established treatment option for patients with end-stage heart disease. Most centers use an immunosuppressive regimen consisting of a calcineurin inhibitor (CNI; cyclosporine or tacrolimus), together with an antiproliferative agent (azathioprine or mycophenolate mofetil) with or without corticosteroids. However, long-term CNI therapy is associated with neph- rotoxicity, renal impairment is present in 31% of recipients at 5 years after transplantation. 1 Newer immunosuppressive agents have become avail- able, which are not nephrotoxic, namely, mycophenolate mofetil, sirolimus, and everolimus. The use of mycopheno- late mofetil and sirolimus in combination has facilitated CNI-free immunosuppression in renal transplantation, 2–6 but currently there is limited information about this ap- proach in heart transplantation. The objectives of this study were to determine whether CNI withdrawal is feasible using a combination of sirolimus and mycophenolate mofetil, and whether this maneuver results in improved renal function after heart transplantation. METHODS A 12-month retrospective analysis of 14 heart transplant patients, who were switched from their CNI to sirolimus between November 2002 to May 2003. The indication for the switch was renal impairment; the mean initial serum creatinine was 321  107 mol/L. The 14 (13 men) patients were switched at a mean of 41.6 (range 1.0 to 138.6) months after transplant. The mean age was 56 years (range 25 to 70). The calcineurin inhibitor, cyclosporine (n = 13) or tacrolimus (n = 1), was discontinued with sirolimus com- From the Department of Cardiothoracic Transplantation, Harefield Hospital, Harefield Middlesex, United Kingdom. Address reprint requests to H. Lyster, Department of Cardiotho- racic Transplantation, Harefield Hospital, Hill End Road, Harefield, Middlesex, UB96JH, United Kingdom. E-mail: h.lyster@rbh. nthames.nhs.uk © 2004 by Elsevier Inc. All rights reserved. 0041-1345/04/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2004.10.062 Transplantation Proceedings, 36, 3167–3170 (2004) 3167