title: Initial experience with sirolimus and mycophenolate mofetil for renal rescue from cyclosporine nephrotoxicity after heart transplantation.
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 micromol/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 complicated 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.
authors.affiliation: Department of Cardiothoracic Transplantation, Harefield Hospital, Harefield Middlesex, United Kingdom. h.lyster@rbh.nthames.nhs.uk
authors.forename: H
authors.initials: H
authors.lastname: Lyster
authors.forename: G
authors.initials: G
authors.lastname: Panicker
authors.forename: N
authors.initials: N
authors.lastname: Leaver
authors.forename: N R
authors.initials: NR
authors.lastname: Banner
mesh_terms: D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007677:Kidney Function Tests; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus