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 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.
Hauser
Peter
P
Department of Nephrology, University of Vienna, Austria.
Schwarz
Christoph
C
Mitterbauer
Christa
C
Regele
Heinz M
HM
Mühlbacher
Ferdinand
F
Mayer
Gert
G
Perco
Paul
P
Mayer
Bernd
B
Meyer
Timothy W
TW
Oberbauer
Rainer
R
D058186:Acute Kidney Injury / Q000517:prevention & control; D000328:Adult; D000368:Aged; D001706:Biopsy; D002102:Cadaver; D020869:Gene Expression Profiling; D006085:Graft Survival / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D016030:Kidney Transplantation / Q000502:physiology*; D019520:Living Donors; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D014019:Tissue Donors