Gene-Expression Profiles and Age of Donor Kidney Biopsies Obtained Before Transplantation Distinguish Medium Term Graft Function

Stanford University, Palo Alto, California, United States
Transplantation (Impact Factor: 3.83). 04/2007; 83(8):1048-54. DOI: 10.1097/
Source: PubMed


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.
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.
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.
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.

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    • "Kainz et al. conducted a genome-wide analysis of donor organs before transplantation and at 1 year post-transplant dividing the groups based on good or poor graft function [28]. They identified 52 genes that were differentially expressed between the two groups [28]. The genes that were upregulated in subjects with poor graft function were related to immune system/complement pathway, signal transduction, and oxidative stress [28]. "
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