E-GEOD-1743 - Transcription profiling of human kidneys from chronic allograft nephropathy patients treated with either cyclosporin or sirolimus immunosuppression regimes

Status
Submitted on 9 September 2004, released on 25 August 2007, last updated on 27 March 2012
Organism
Homo sapiens
Samples (41)
Array (1)
Description
Background: Despite significant improvements in short-term kidney transplant survival, comparable increases in 5 and 10-year outcomes have not been achieved. Chronic allograft nephropathy (CAN) is a major cause of late graft loss. Toxic nephropathy and inadequate long-term immunosuppression are possible factors. 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. Methods: Sixty-one kidney recipients received mycophenolate mofetil (MMF), and prednisone (P). Randomized patients received 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. Findings: Comparing sirolimus/MMF/P to cyclosporine/MMF/P at two years, there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dl; p=0.008), significantly higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 cc/min; p=0.008), iothalamate GFR (60.6 vs. 49.2 cc/min; p= 0.018), and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p=0.013). Regression analysis of calculated GFR’s 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 of kidney biopsies with higher Banff CAN scores confirmed significant up regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. Interpretation: At two years the sirolimus-treated patients have better renal transplant function, a diminished prevalence of CAN, and down regulated expression of genes responsible for the progression of CAN. All may provide for an alternative natural history with improved graft survival.
Experiment types
transcription profiling by array, clinical treatment, co-expression
Contact
Citation
De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function at two years. Stuart M Flechner, Sunil M Kurian, Kim Solez, Daniel J Cook, James T Burke, Hank Rollin, Jennifer A Hammond, Thomas Whisenant, Caroline M Lanigan, Steven R Head, Daniel R Salomon. Am J Transplant 4(11):1776-85 (2004)
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-1743.idf.txt
Sample and data relationshipE-GEOD-1743.sdrf.txt
Processed data (1)E-GEOD-1743.processed.1.zip
Array designA-AFFY-33.adf.txt
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