Intrarenal cytokine and chemokine gene expression and kidney graft outcome.
OBJECTIVE
Proinflammatory cytokines are thought to play an important role in various kidney graft diseases resulting in interstitial fibrosis and tubular atrophy frequently found in case biopsies. To explore the role of various cytokines and chemokines in the long-term graft outcome, the transcription patterns of their genes in kidney allograft biopsies were evaluated.


METHODS
The real-time RT-PCR was used to identify intragraft mRNA expression of cytokines and chemokines in 74 kidney graft recipients and the results were correlated with histological and clinical parameters and long-term graft outcome.


RESULTS
We observed up-regulated IL-10 (p < 0.001), TGF-beta1, IL-6, MCP-1, RANTES (p < 0.01) and TNF-alpha (p < 0.05) mRNA expression in patients with chronic allograft nephropathy (CAN) as compared to controls. There were positive correlations between the mRNA expression of IL-6 (p < 0.001), IL-10 (p < 0.01), TNF-alpha, MCP-1 (p < 0.05) and the proteinuria. The up-regulation of intrarenal MCP-1 in patients with CAN increased the risk for the graft failure within the next 42 months (OR 5.1, p < 0.05). Kaplan-Meier survival analysis revealed that proteinuria and higher intragraft expression of TGF-beta1 and MCP-1 predict a poor kidney graft outcome.


CONCLUSIONS
Expression patterns of intrarenal proinflammatory genes might discriminate patients at a higher risk for the earlier allograft failure.
Hribova
Petra
P
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Lacha
Jiri
J
Kotsch
Katja
K
Volk
Hans-Dieter
HD
Brabcova
Irena
I
Skibova
Jelena
J
Vitko
Stefan
S
Viklicky
Ondrej
O
D000328:Adult; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000502:physiology; D006084:Graft Rejection / Q000235:genetics / Q000378:metabolism*; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D018925:Chemokines; D016207:Cytokines