De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function at two years

Am J Transplant. 2004 Nov;4(11):1776-85. doi: 10.1111/j.1600-6143.2004.00627.x.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Calcineurin Inhibitors
  • Cyclosporine / therapeutic use*
  • Graft Survival / physiology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Inflammation
  • Kidney Function Tests
  • Kidney Transplantation / pathology
  • Kidney Transplantation / physiology*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Prednisone / therapeutic use
  • Sirolimus / therapeutic use*
  • Time Factors
  • Transplantation, Homologous
  • Treatment Outcome


  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Prednisone
  • Sirolimus