Journal Article

Dialysis-related systemic microinflammation is associated with specific genomic patterns

Gianluigi Zaza, Paola Pontrelli, Giovanni Pertosa, Simona Granata, Michele Rossini, Silvia Porreca, Frank J. T. Staal, Loreto Gesualdo, Giuseppe Grandaliano and Francesco Paolo Schena

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 5, pages 1673-1681
Published in print May 2008 | ISSN: 0931-0509
Published online November 2007 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfm804
Dialysis-related systemic microinflammation is associated with specific genomic patterns

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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.

Keywords: haemodialysis; microarray; microinflammation; peritoneal dialysis

Journal Article.  5514 words.  Illustrated.

Subjects: Nephrology

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