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Series GSE43974 Query DataSets for GSE43974
Status Public on Apr 02, 2015
Title Pathways for intervention to optimize donor organ quality uncovered: a genome wide gene expression study
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Background: Strategies to improve long term renal allograft survival have been directed to recipient dependent mechanisms of renal allograft injury. In contrast, no such efforts have been made to optimize organ quality in the donor. In order to get insight into the deleterious gene pathways expressed at different time points during deceased kidney transplantation, transcriptomics was performed on kidney biopsies from a large cohort of deceased kidney transplants.
Methods: A total of 554 kidney biopsies were taken from living and deceased donor kidneys at donation, after cold ischemia and after reperfusion. Transcriptomics by means of whole genome micro-array analyses followed by functional pathway analyses was performed.
Results: Oxidative stress and complement- and coagulation pathways were uncovered as potential pathways for intervention in deceased donors. No genes were found to be differentially expressed between donation and cold ischemia. After reperfusion, pathways related to oxidative stress, NOD-like signalling, MAPK, cytokine-cytokine receptor, complement- and-coagulation and chemokines were enriched in kidneys from deceased organ donors. Pathways related to prolonged and worsening deprivation of oxygen were associated with delayed graft function of DCD grafts.
Conclusions: The present study reveals oxidative stress and enrichment of complement and coagulation pathways in deceased donor kidneys. Future intervention therapies to optimize donor organ quality and prolong allograft survival should target oxidative stress and innate immune activation in the donor.
 
Overall design Total RNA was isolated from kidney biopsies. Biopsies were taken from deceased brain-dead kidney donors (n=81) and deceased cardiac dead donors (n=37) before organ retrieval. From another transplant cohort, kidney biopsies were taken after cold ischemia and after reperfusion of a brain-dead donor kidney (n=67 paired, 43-38 unpaired) or cardiac-dead donor kidney (n=29 paired, 24-35 unpaired). Living donors kidney biopsies (n=37) and paired living reperfusion biopsies (n=34) served as controls.
Three timepoints:
T1 = Kidney biopsy taken before organ retrieval in deceased donors
T2 = After cold ischemia
T3 = 60 minutes after reperfusion
 
Contributor(s) Damman J, Seelen MA
Citation(s) 25427168
Submission date Jan 31, 2013
Last update date Aug 13, 2018
Contact name Jeffrey Damman
Organization name University Medical Center Groningen
Department Pathology
Street address Hanzeplein 1
City Groningen
ZIP/Postal code 9713 GZ
Country Netherlands
 
Platforms (1)
GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Samples (554)
GSM1075188 Kidney_donor_BD_T1_1
GSM1075189 Kidney_donor_BD_T3_1
GSM1075190 Kidney_donor_DCD_T3_1
Relations
BioProject PRJNA188389

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43974_RAW.tar 26.2 Mb (http)(custom) TAR
GSE43974_non-normalized_data.txt.gz 191.3 Mb (ftp)(http) TXT
GSE43974_paired_analyses_DBD_DCD_Living.xls.gz 6.3 Kb (ftp)(http) XLS
Raw data is available on Series record
Processed data included within Sample table

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