Genome-wide gene-expression patterns of donor kidney biopsies distinguish primary allograft function

Roughly 25% of cadaveric, but rarely living donor renal transplant recipients, develop postischemic acute renal failure, which is a main risk factor for reduced long-term allograft survival. An accurate prediction of recipients at risk for ARF is not possible on the basis of donor kidney morphology...

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Bibliographic Details
Published in:Laboratory investigation 2004-03, Vol.84 (3), p.353-361
Main Authors: Hauser, Peter, Schwarz, Christoph, Mitterbauer, Christa, Regele, Heinz M, Mühlbacher, Ferdinand, Mayer, Gert, Perco, Paul, Mayer, Bernd, Meyer, Timothy W, Oberbauer, Rainer
Format: Article
Language:English
Subjects:
Acute Kidney Injury - prevention & control
Adult
Aged
ARF
array
Biological and medical sciences
Biopsy
Biotechnology
Cadaver
donor
Fundamental and applied biological sciences. Psychology
gene expression
Gene Expression Profiling
Graft Survival - genetics
Humans
Inflammation - prevention & control
Investigative techniques, diagnostic techniques (general aspects)
Kidney Transplantation - physiology
Laboratory Medicine
Living Donors
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Oligonucleotide Array Sequence Analysis
Pathology
research-article
Tissue Donors
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Summary:Roughly 25% of cadaveric, but rarely living donor renal transplant recipients, develop postischemic acute renal failure, which is a main risk factor for reduced long-term allograft survival. An accurate prediction of recipients at risk for ARF is not possible on the basis of donor kidney morphology or donor/recipient demographics. We determined the genome-wide gene-expression pattern using cDNA microarrays in three groups of 36 donor kidney wedge biopsies: living donor kidneys with primary function, cadaveric donor kidneys with primary function and cadaveric donor kidneys with biopsy proven acute renal failure. The descriptive genes were characterized in gene ontology terms to determine their functional role. The validation of microarray experiments was performed by real-time PCR. We retrieved 132 genes after maxT adjustment for multiple testing that significantly separated living from cadaveric kidneys, and 48 genes that classified the donor kidneys according to their post-transplant course. The main functional roles of these genes are cell communication, apoptosis and inflammation. In particular, members of the complement cascade were activated in cadaveric, but not in living donor kidneys. Thus, suppression of inflammation in the cadaveric donor might be a cheap and promising intervention for postischemic acute renal failure.
ISSN:0023-6837
1530-0307
DOI:10.1038/labinvest.3700037