Expression profiling on chronically rejected transplant kidneys.
BACKGROUND
Chronic transplant nephropathy remains a poorly defined inflammatory process that limits the survival rate of most renal transplants. We analyzed the gene profile of chronically rejected kidney transplants to identify candidate genes that characterize chronic transplant nephropathy.


METHODS
To distinguish genes present in normal renal tissue or specific for end-stage renal failure, we compared the gene profiles of 13 chronically rejected kidney transplants with 16 normal kidneys and 12 end-stage polycystic kidneys using a 7K human cDNA microarray. After elimination of genes with signals close to background, 2190 genes were available for statistical analysis.


RESULTS
More than 20% of the examined genes were significantly regulated when compared with the expression level of normal renal tissue (P<0.0003). Hierarchic clustering based on 571 genes differentiated normal and transplant tissue, and transplant and polycystic kidney tissue. Most of these genes encoded proteins involved in cellular metabolism, transport, signaling, transcriptional activation, adhesion, and the immune response. Notably, comprehensive gene profiling of chronically rejected kidneys revealed two distinct subsets of chronically rejected transplants. Neither clinical data nor histology could explain this genetic heterogeneity.


CONCLUSIONS
Microarray analysis of rejected kidneys may help to define different entities of transplant nephropathy, reflecting the multifactorial cause of chronic rejection.
Donauer
Johannes
J
Department of Medicine, University Hospital Freiburg, Germany.
Rumberger
Brigitta
B
Klein
Marinella
M
Faller
Daniel
D
Wilpert
Jochen
J
Sparna
Titus
T
Schieren
Gisela
G
Rohrbach
Rolf
R
Dern
Peter
P
Timmer
Jens
J
Pisarski
Przemyslaw
P
Kirste
Gunter
G
Walz
Gerd
G
D000328:Adult; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D007690:Polycystic Kidney Diseases / Q000235:genetics; D011183:Postoperative Complications