Transcriptome analysis in patients with chronic kidney disease on hemodialysis disclosing a key role for CD16+CX3CR1+ monocytes.

UNLABELLED: The risk for cardiovascular morbidity and mortality is increased in chronic kidney disease; in this process micro-inflammation plays an essential role. Responsible mechanisms remain to a large extent unidentified. In this pilot study transcriptome analysis of peripheral blood monocytes was used to identify in an unprejudiced manner which factors could be discriminative for cardiovascular disease in patients with chronic kidney disease on hemodialysis. Forty gender- and age-matched, non-diabetic, non-smoking subjects with CRP < 20 mg/L were recruited: 9 healthy controls, 11 patients with eGFR > 60 mL/min/1.73m2 and a history of cardiovascular event (CVE), 10 patients with chronic kidney disease stage 5 on hemodialysis without previous cardiovascular event (CKD5HD) and 10 with a previous cardiovascular event (CKD5HD/CVE). Monocytes were isolated and their mRNA was submitted to focused transcriptome analysis using a macroarray platform containing ca. 700 genes associated with macrophage functional capacity. The macroarray data indicated 9 genes (8 upregulated and 1 downregulated) with a significant differential expression in CKD5HD/CVE vs. CVE alone, after excluding genes differentially expressed in CKD5HD vs.

CONTROL: For FCGR3A (CD16) and CX3CR1 (chemokine receptor) the upregulation vs. control and vs. CVE could be confirmed by quantitative RT-PCR for all CKD5HD patients. Furthermore, CX3CR1 relative expression on monocytes correlated with CRP. Flow cytometric analysis of purified monocytes confirmed a significant increase in the percentage of CD16 positive monocytes in all CKD5HD patients vs. control and CVE. The present study indicates the importance of a specific pro-inflammatory monocyte subpopulation, positive for CD16 and the co-expressed chemokine receptor, CX3CR1, discriminative for CKD5HD patients.