Presented at the American Transplant congress, Boston, Massachusetts, May 16, 2004.
De Novo Kidney Transplantation Without Use of Calcineurin Inhibitors Preserves Renal Structure and Function at Two Years
Article first published online: 16 SEP 2004
American Journal of Transplantation
Volume 4, Issue 11, pages 1776–1785, November 2004
How to Cite
Flechner, S. M., Kurian, S. M., Solez, K., Cook, D. J., Burke, J. T., Rollin, H., Hammond, J. A., Whisenant, T., Lanigan, C. M., Head, S. R. and Salomon, D. R. (2004), De Novo Kidney Transplantation Without Use of Calcineurin Inhibitors Preserves Renal Structure and Function at Two Years. American Journal of Transplantation, 4: 1776–1785. doi: 10.1111/j.1600-6143.2004.00627.x
- Issue published online: 16 SEP 2004
- Article first published online: 16 SEP 2004
- Received 19 May 2004, revised and accepted for publication 28 July 2004
- Chronic allograft nephropathy;
- gene expression;
- kidney transplantation;
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.