Project description:Patients with combined heart and renal failure, also termed the cardiorenal syndrome (CRS), have high cardiovascular morbidity and mortality. Several key connectors between heart and kidney have been recognized, such as oxidative stress, inflammation, the renin-angiotensin system and the sympathetic nervous system. Monocytes are key players in the development of atherosclerosis and may act as a biosensor to detect changes in the systemic environment. Anemia, which occurs frequently in CRS, is partly due to an absolute and/or relative erythropoietin (EPO) deficiency. Until now, EPO treatment has largely been used to treat (renal) anemia, but recent research also showed beneficial non-hematopoietic effects such as anti-inflammatory and anti-oxidative capacities. The hypothesis of the present study was that 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. 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. 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. The supplementary file 'GSE17582_non-normalized_data.txt' contains non-normalized data for Samples GSM438053-GSM438100.

Project description:Background and objectives: This report describes an unusual presentation of severe hypertension (HTN) in a subset of pediatric kidney recipients treated with a steroid avoidance pediatric renal transplantation protocol. The HTN was secondary to atypical, reno-vascular abnormalities (RVA) of the transplanted vasculature, temporally associated with erythropoietin (EPO) use. Design, setting, participants, and measurements: To investigate the clinical significance underlying this event, a retrospective clinical study of 100 pediatric renal transplants was undertaken (50 steroid-free and 50 matched steroid-based controls), with peripheral blood transcriptional analysis of four RVA patients and controls. Results: Regardless of a higher observed incidence of anemia (p < 0.001) and greater overall EPO usage in the first post-transplant year in steroid-free patients, the incidence of new-onset HTN at one yr was significantly less in the steroid-free cohort (p = 0.03). Nevertheless, early EPO (first week post-transplant) was significantly associated with the combinatory findings of new-onset HTN (p = 0.03) and RVA (p = 0.007). Molecular mechanisms of RVA injury were investigated further by peripheral blood cDNA microarray gene expression profiling. A panel of 42 transcripts differentiated patients with RVA and HTN from three sets of matched controls, with and without HTN and EPO use, with 100% concordance (p < 0.001). The biological processes governed by these significant genes suggest a role for EPO regulation of growth factor receptor ubiquitination as a putative mechanism for renal vascular injury. Conclusion: This study cautions against the use early post-transplant use of EPO in immunosuppression regimens with steroid minimization/avoidance, which may have an increased incidence of post-transplant anemia. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: patient with high blood pressure Keywords: Logical Set Using regression correlation

Project description:Background and objectives: This report describes an unusual presentation of severe hypertension (HTN) in a subset of pediatric kidney recipients treated with a steroid avoidance pediatric renal transplantation protocol. The HTN was secondary to atypical, reno-vascular abnormalities (RVA) of the transplanted vasculature, temporally associated with erythropoietin (EPO) use. Design, setting, participants, and measurements: To investigate the clinical significance underlying this event, a retrospective clinical study of 100 pediatric renal transplants was undertaken (50 steroid-free and 50 matched steroid-based controls), with peripheral blood transcriptional analysis of four RVA patients and controls. Results: Regardless of a higher observed incidence of anemia (p < 0.001) and greater overall EPO usage in the first post-transplant year in steroid-free patients, the incidence of new-onset HTN at one yr was significantly less in the steroid-free cohort (p = 0.03). Nevertheless, early EPO (first week post-transplant) was significantly associated with the combinatory findings of new-onset HTN (p = 0.03) and RVA (p = 0.007). Molecular mechanisms of RVA injury were investigated further by peripheral blood cDNA microarray gene expression profiling. A panel of 42 transcripts differentiated patients with RVA and HTN from three sets of matched controls, with and without HTN and EPO use, with 100% concordance (p < 0.001). The biological processes governed by these significant genes suggest a role for EPO regulation of growth factor receptor ubiquitination as a putative mechanism for renal vascular injury. Conclusion: This study cautions against the use early post-transplant use of EPO in immunosuppression regimens with steroid minimization/avoidance, which may have an increased incidence of post-transplant anemia. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: patient with high blood pressure Keywords: Logical Set

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Effect of two weeks erythropoietin treatment on monocyte transcriptomes of cardiorenal patients

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