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Transcription profiling of human stable end-stage renal disease patients reveals nocturnal hemodialysis improves erythropoietin responsiveness

ABSTRACT: Nocturnal home hemodialysis (NHD) [5 â 6 times a week, 6-8 hours per session] augments uremia clearance and is associated with an increase in hemoglobin level. We have used microarray to have a global image of the changes at the gene expression. Experiment Overall Design: Sixteen stable end-stage renal disease patients (age: 47 Â± 2 years; 9M) [mean Â± SEM] were studied. Total RNA (TRNA) was isolated from whole blood before and after 3 months of established NHD. Gene expression before and after NHD was acquired through hybridizations on Human HG-U133_PLUS2 GeneChip and genes with differential gene expression were identified.

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PROVIDER: S-DIXA-D-1004 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:Cardiovascular disease is the major cause of morbidity and death in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Patients with CKD and ESRD are at high risk for myocardial dysfunction, ischemia and heart failure. The mechanisms linking impaired renal function and increased risk for cardiovascular diseases, however, remain elusive. In addition, conventional therapeutics proven effective in reducing cardiovascular events in general population fail to provide similar benefits in uremic patients. There is a clear need to identify novel mediators of cardiovascular complications in uremic patients to provide insights into the pathogenesis, to tailor clinical care based on cardiovascular risks, and to develop new therapeutic strategies. It has become increasingly clear that the transcription of the eukaryotic genome is far more pervasive and complex than previously appreciated. While the expression of messenger RNAs (mRNAs) and microRNAs (miRNAs) account for only ~1% of all transcribed species, up to 90% of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs), a heterogeneous group of non-coding transcripts longer than 200 nucleotides. LncRNAs have been shown to be functional and involved in specific physiological and pathological processes through epigenetic, transcriptional and post-transcriptional mechanisms. While the roles of lncRNAs in human diseases including cancer and neurodegenerative disorders are beginning to emerge, it remains unclear how lncRNA regulation contributes to cardiovascular complications in patients with renal dysfunction. In this proposal, we seek to apply next-generation sequencing technology to investigate circulating (plasma) lncRNA expression in control subjects and in patients with CKD and ESRD. We will test the hypothesis that circulating lncRNA expression signature can reflect the underlying kidney disease states in patients with CKD and ESRD. In addition, we will determine if circulating lncRNA expression signature could be a sensitive and specific biomarker to predict adverse cardiovascular events in patients with ESRD.

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Transcription profiling of human stable end-stage renal disease patients reveals nocturnal hemodialysis improves erythropoietin responsiveness

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