Dialysis-related systemic microinflammation is associated with specific genomic patterns.
BACKGROUND
Although several reports have focused on the clinical importance of the systemic microinflammatory state in the uraemic population, the relationship between the activation of a specific transcriptome and the development of this condition is still not completely defined.


METHODS
Thirty haemodialysis (HD), 30 peritoneal dialysis (PD) and 30 chronic kidney disease (CKD) patients were enrolled in our study. For all patients, serum C-reactive protein (CRP) and ferritin levels were determined. In addition, the expression level of 234 inflammatory responses and oxidative stress pathway genes was measured, using oligonucleotide microarray chips (HG-U133A, Affymetrix), in peripheral blood mononuclear cells of 24 randomly selected patients (8 HD, 8 PD and 8 CKD).


RESULTS
HD patients demonstrated higher CRP and ferritin levels compared to PD and CKD patients (P < 0.001). Statistical analysis identified 10 genes able to discriminate CKD from HD and PD patients (FDR = 5%, P < 0.001) and significantly correlated to CRP levels. All together, these genes were able to predict inflammation with an accuracy of 87% (P < 0.001). Among the selected genes there were those encoding for key regulators of inflammation and oxidative stress (e.g. RELA, GSS). Interestingly, only three inflammatory genes (MIF, IL8RB and CXCL12) were still significantly associated with inflammation when included in a multivariate analysis. RT-PCR for RELA, MIF, CXCL12 and western blots for IL8RB and GSS, using 66 patients, validated the microarray results.


CONCLUSIONS
This study may help to better understand the physiopathology of the systemic inflammatory state in CKD and dialysis patients and to identify new target genes potentially useful for future bio-molecular studies and therapeutic approaches.
Zaza
Gianluigi
G
Division of Nephrology, Department of Emergency and Transplantation, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Pontrelli
Paola
P
Pertosa
Giovanni
G
Granata
Simona
S
Rossini
Michele
M
Porreca
Silvia
S
Staal
Frank J T
FJ
Gesualdo
Loreto
L
Grandaliano
Giuseppe
G
Schena
Francesco Paolo
FP
D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics; D005260:Female; D005293:Ferritins / Q000378:metabolism; D020869:Gene Expression Profiling; D005981:Glutathione Synthase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000235:genetics; D015854:Up-Regulation
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D008263:Macrophage Migration-Inhibitory Factors; C498143:RELA protein, human; D023063:Receptors, Interleukin-8B; D051996:Transcription Factor RelA; D002097:C-Reactive Protein; D005293:Ferritins; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; D005981:Glutathione Synthase