Sirolimus in combination with tacrolimus is associated with worse renal allograft survival compared to mycophenolate mofetil combined with tacrolimus

Herwig Ulf Meier-Kriesche, Jesse D. Schold, Titte R. Srinivas, Richard J. Howard, Shiro Fujita, Bruce Kaplan

    Research output: Contribution to journalArticlepeer-review

    106 Scopus citations

    Abstract

    Cyclosporine (CsA) nephrotoxicity is enhanced by sirolimus (SRL). Tacrolimus is perceived to be less nephrotoxic than CsA, and therefore, CsA has been largely replaced by tacrolimus (TAC) when calcineurin inhibitors are used with SRL. We analyzed 44 915 adult renal transplants in the Scientific Renal Transplant Registry (SRTR) from 2000 to 2004. Three thousand five hundred twenty-four (7.8%) patients received a baseline immunosuppressive regimen of TAC/SRL, with an inferior overall (log-rank p < 0.001) and death-censored graft survival (p < 0.001) as compared to TAC/MMF (N = 27 007). This effect was confirmed in multivariate Cox models; the adjusted hazard ratio (AHR) for overall graft loss with TAC/SRL was 1.47 (95% CI = 1.32, 1.63) and for CsA/SRL 1.38 (95% CI = 1.20, 1.59) relative to TAC/MMF. These effects were most apparent in high-risk transplants. Six-month acute rejection rates were low (11.5-12.6%) and not different between groups. In summary, national data indicate that TAC/SRL as compared to TAC/MMF is associated with significantly worse renal allograft survival in all subgroups of patients and, in particular, higher-risk transplants. These results have to be interpreted in the context of the inherent limitations of any retrospective database analysis and evaluated in context with data from prospective clinical trials.

    Original languageEnglish (US)
    Pages (from-to)2273-2280
    Number of pages8
    JournalAmerican Journal of Transplantation
    Volume5
    Issue number9
    DOIs
    StatePublished - Sep 2005

    Keywords

    • Kidney
    • Mycophenolate mofetil
    • Sirolimus
    • Survival
    • Tacrolimus
    • Transplant

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Transplantation
    • Pharmacology (medical)

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