Reduced exposure to calcineurin inhibitors in renal transplantation.

Henrik Ekberg, Helio Tedesco-Silva, Alper Demirbas, Stefan Vítko, Björn Nashan, Alp Gürkan, Raimund Margreiter, Christian Hugo, Josep M Grinyó, Ulrich Frei, Yves Vanrenterghem, Pierre Daloze, Philip F Halloran

    Research output: Contribution to journalArticlepeer-review

    1416 Citations (SciVal)

    Abstract

    BACKGROUND: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. METHODS: We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival. RESULTS: The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%). CONCLUSIONS: A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).
    Original languageEnglish
    Pages (from-to)2562-2575
    JournalNew England Journal of Medicine
    Volume357
    Issue number25
    DOIs
    Publication statusPublished - 2007

    Subject classification (UKÄ)

    • Urology and Nephrology

    Keywords

    • Adrenal Cortex Hormones: administration & dosage
    • Adrenal Cortex Hormones: therapeutic use
    • Antibodies
    • Monoclonal: administration & dosage
    • Calcineurin: antagonists & inhibitors
    • Cyclosporine: administration & dosage
    • Diabetes Mellitus: etiology
    • Graft Rejection: prevention & control
    • Enzyme Inhibitors: administration & dosage
    • Immunoglobulin G: administration & dosage
    • Immunosuppressive Agents: adverse effects
    • Immunosuppressive Agents: administration & dosage
    • Immunosuppressive Agents: therapeutic use
    • Mycophenolic Acid: analogs & derivatives
    • Mycophenolic Acid: administration & dosage
    • Prednisone: administration & dosage
    • Sirolimus: administration & dosage
    • Sirolimus: adverse effects
    • Tacrolimus: administration & dosage

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