Sirolimus and tacrolimus in clinical cardiac transplantation

Abstract

Aim: The nephrotoxicity associated with calcineurin-inhibitors is dose dependent. The goal of this study is to determine whether a combination of tacrolimus and sirolimus will allow us to reduce the level of tacrolimus in heart transplant recipients, thus reduce the degree of tacrolimus-induced renal toxicity. Methods: Since March 2000, we have treated 12 consecutive primary heart transplant recipients with a combination of tacrolimus, sirolimus and steroids (Group I). The clinical data of these patients were compared with those of 10 patients who received tacrolimus, mycophenolate mofetil and steroids (Group II). The levels of sirolimus (24 hour trough) amd MMF were maintained at 8.0-12.0 ng/ml, and 1.5-3.0 ng/ml, respectively. A steroids tapering schedule was similar between groups. Results: The number of rejection episodes, tacrolimus doses and levels, serum creatinine, platelet counts, cholesterol and triglycerides of the two groups are presented in the table. There is no difference in the freedom from rejection (grade 2; Gr I: 72 13%, Gr II: 71 13%) or patient survival; however the rejection (grade 2) episode/patient, serum creatinine (at 2 weeks) and mean tacrolimus levels (at 3 months) are higher in group II (see Table). Conclusion: The short-term outcome of cardiac recipients under tacrolimus/sirolimus/steroids immunosuppressive regimen compares favorably with those under the tacrolimus/mycophenolate mofetil/steroids regimen. The lower tacrolimus level in the sirolimus group may translate into less nephrotoxicity.