The first aim was to investigate whether this short term treatment revealed non-hematopoietic EPO effects. The second aim was to address whether EPO dampens expression of genes involved in inflammation and oxidative stress. Given the variable response to EPO, the third aim was to test whether baseline gene expression profiles or the acute gene expression modulation by EPO are associated with EPO resistance.

Monocyte gene expression profiles of cardiorenal patients compared to healthy controls reflect the systemic nature of CRS and are responsive to short-term treatment with Epo.

This study was part of a larger clinical trial in which hematopoietic and non-hematopoietic effects of EPO treatment for short and long term are assessed in CRS patients. Therefore, patients were randomized into 3 groups: (1) EPO, patients are kept on baseline low hemoglobin levels by phlebotomy for 6 months; (2) EPO, patients may rise in hemoglobin levels to defined maximum for 6 months; (3) No EPO. This gene expression analysis is focussed on EPO's short-term (2wk) effects in a subset of included patients. Group (1) and (2) were grouped for analysis, since both groups received EPO and no phlebotomy had been performed in the first 2 weeks. Monocytes were positively isolated from peripheral whole blood with CD14+ immunomagnetic beads. Total RNA was isolated and prepared for genome wide analyses using Illumina HumanRef8 V3.0 Beadchips. In total, 48 arrays were analyzed including 12 healthy controls, 18 CRS patients at baseline and 2 weeks after study enrollment. Twelve out of 18 patients received EPO during the two weeks.

Braam B, Gaillard CA, Verhaar MC, Jie KE, Wesseling S, van der Putten K