Gene-expression profiles and age of donor kidney biopsies obtained before transplantation distinguish medium term graft function.
BACKGROUND
Donor factors such as age profoundly influence long-term graft function after cadaveric renal transplantation, but the molecular signature of these aspects in the allograft remains unknown.


METHODS
We analyzed the genome-wide gene expression signature of donor kidney biopsies of different ages obtained before transplantation. Subsequent analysis compared expression profiles from allografts with excellent function versus impaired function at 1 yr after engraftment. Differential expression profiles were analyzed on the level of molecular function and biologic role, as well as by analysis of co-regulation through transcription factors, regulatory networks, and protein-protein interaction data utilizing extended bioinformatics.


RESULTS
The 15 subjects with excellent transplant function defined as calculated GFR>or=45 mL/min/1.73 m2 at 1 yr exhibited a distinctly different gene expression profile than the matched 16 subjects with impaired function defined as calculated GFR<45 mL/min/1.73 m2. Donor kidneys from recipients with impaired allograft function showed activation of genes mainly belonging to the functional classes of immunity, signal transduction, and oxidative stress response. Two-thirds of these genes exhibited at least one protein interacting partner, suggesting choreographed intracellular events differentiating the two recipient groups. However, donor age may have confounded some of the associations found between gene profiles and graft function.


CONCLUSIONS
In summary, a distinctive gene expression profile in the donor kidney at transplantation together with donor age predicts medium term allograft function in recipients of cadaveric allografts.
Kainz
Alexander
A
Department of Nephrology, KH Elisabethinen Linz, and Medical University of Vienna, Vienna, Austria.
Perco
Paul
P
Mayer
Bernd
B
Soleiman
Afschin
A
Steininger
Rudolf
R
Mayer
Gert
G
Mitterbauer
Christa
C
Schwarz
Christoph
C
Meyer
Timothy W
TW
Oberbauer
Rainer
R
D000328:Adult; D000375:Aging / Q000235:genetics* / Q000502:physiology*; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006085:Graft Survival / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014019:Tissue Donors