Gene expression patterns in deceased donor kidneys developing delayed graft function after kidney transplantation.
BACKGROUND
Delayed graft function (DGF) after kidney transplantation (KTx) ranges between 2% and 50%. The mechanisms leading to DGF deserve special interest because DGF exerts negative influences on long-term outcomes. We studied gene expression profiles in deceased donor kidney (DDK) biopsies with and without DGF.


METHODS
Gene expression profiling was performed on donor kidney tissues from 33 DDK with the use of microarrays. DDK were classified as grafts with immediate function (non-DGF; n=21) and grafts with DGF (n=12). DGF was defined as a dialysis requirement in the first week after transplantation. Demographic donor and recipient information was collected. The robust-multiarray average method was used to estimate probe set expression summaries. Logistic regression was used to identify genes significantly associated with DGF development.


RESULTS
Patients were followed for 3 months after KTx. Thirty-eight probe sets (n=36 genes) were univariably differentially expressed in DDK with DGF when compared with DDK with non-DGF (alpha=0.001). Sixty-nine probe sets (n=65 genes) were differentially expressed in DDK with DGF when compared with DDK with non-DGF after adjusting for cold ischemia time (alpha=0.001). Gene ontology terms classified the overexpressed genes in DDK with DGF as principally related to cell cycle/growth (e.g., IGFBP5, CSNK2A2), signal transduction (e.g., RASGRP3), immune response (e.g., CD83, BCL3, MX1), and metabolism (e.g., ENPP4, GBA3). TNFRSF1B was overexpressed in DDK with DGF.


CONCLUSIONS
Cold ischemia time was a predictor of DGF independently of the preservation method. We identified a set of 36 genes candidates of DGF in DDK, with genes involved in the inflammatory response being the more important.
Mas
Valeria R
VR
Division of Transplant, Department of Surgery, Virginia Commonwealth University, Richmond, VA, USA.
Archer
Kellie J
KJ
Yanek
Kenneth
K
Dumur
Catherine I
CI
Capparuccini
Maria I
MI
Mangino
Martin J
MJ
King
Anne
A
Gibney
Eric M
EM
Fisher
Robert
R
Posner
Marc
M
Maluf
Daniel
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002102:Cadaver; D002874:Chromosome Mapping; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007668:Kidney; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D006680:HLA Antigens; D012313:RNA