De Novo Kidney Transplantation Without Use of Calcineurin Inhibitors Preserves Renal Structure and Function at Two Years

Authors

  • Stuart M. Flechner,

    Corresponding author
    1. Section of Renal Transplantation, Transplant Center, and Allogen Laboratories, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
      *Corresponding author: Stuart M. Flechner, flechns@ccf.org
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  • Sunil M. Kurian,

    1. DNA Array Core Facility, and the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
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  • Kim Solez,

    1. Department of Pathology, University of Alberta, Edmonton, Alberta, Canada
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  • Daniel J. Cook,

    1. Section of Renal Transplantation, Transplant Center, and Allogen Laboratories, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
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  • James T. Burke,

    1. Transplant Immunology, Wyeth Research, Paris, France
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  • Hank Rollin,

    1. Section of Renal Transplantation, Transplant Center, and Allogen Laboratories, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
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  • Jennifer A. Hammond,

    1. DNA Array Core Facility, and the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
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  • Thomas Whisenant,

    1. DNA Array Core Facility, and the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
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  • Caroline M. Lanigan,

    1. DNA Array Core Facility, and the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
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  • Steven R. Head,

    1. DNA Array Core Facility, and the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
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  • Daniel R. Salomon

    1. DNA Array Core Facility, and the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
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  • Presented at the American Transplant congress, Boston, Massachusetts, May 16, 2004.

*Corresponding author: Stuart M. Flechner, flechns@ccf.org

Abstract

We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure and gene expression. Sixty-one kidney recipients treated with basiliximab mycophenolate mofetil (MMF) and prednisone (P) were randomly assigned to concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Comparing sirolimus/MMF/P to cyclosporine/MMF/P there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dL; p = 0.008), higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 mL/min; p = 0.008), iothalamate GFR (60.6 vs. 49.2 mL/min; p = 0.018) and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p = 0.013). Regression analysis of calculated GFRs from 1 to 36 months yielded a positive slope for sirolimus of 3.36 mL/min/year, and a negative slope for cyclosporine of −1.58 mL/min/year (p = 0.008). Gene expression profiles from kidneys with higher Banff chronic allograft nephropathy (CAN) scores confirmed significant up-regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. At 2 years the sirolimus-treated recipients have better renal function, a diminished prevalence of CAN and down-regulated expression of genes responsible for progression of CAN. All may provide for an alternative natural history with improved graft survival.

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