Show simple item record

dc.contributor.authorKhankin, Eliyahu
dc.contributor.authorMutter, Walter Peter
dc.contributor.authorTamez, Hector
dc.contributor.authorYuan, Hai-Tao
dc.contributor.authorKarumanchi, Subbian Ananth
dc.contributor.authorThadhani, Ravi Ishwar
dc.date.accessioned2011-05-02T15:56:45Z
dc.date.issued2010
dc.identifier.citationKhankin, Eliyahu V., Walter P. Mutter, Hector Tamez, Hai-Tao Yuan, S. Ananth Karumanchi, and Ravi Thadhani. 2010. Soluble erythropoietin receptor contributes to erythropoietin resistance in end-stage renal disease. PLoS ONE 5(2): e9246.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4880014
dc.description.abstractBackground: Erythropoietin is a growth factor commonly used to manage anemia in patients with chronic kidney disease. A significant clinical challenge is relative resistance to erythropoietin, which leads to use of successively higher erythropoietin doses, failure to achieve target hemoglobin levels, and increased risk of adverse outcomes. Erythropoietin acts through the erythropoietin receptor (EpoR) present in erythroblasts. Alternative mRNA splicing produces a soluble form of EpoR (sEpoR) found in human blood, however its role in anemia is not known. Methods and Findings: Using archived serum samples obtained from subjects with end stage kidney disease we show that sEpoR is detectable as a 27kDa protein in the serum of dialysis patients, and that higher serum sEpoR levels correlate with increased erythropoietin requirements. Soluble EpoR inhibits erythropoietin mediated signal transducer and activator of transcription 5 (Stat5) phosphorylation in cell lines expressing EpoR. Importantly, we demonstrate that serum from patients with elevated sEpoR levels blocks this phosphorylation in ex vivo studies. Finally, we show that sEpoR is increased in the supernatant of a human erythroleukaemia cell line when stimulated by inflammatory mediators such as interleukin-6 and tumor necrosis factor alpha implying a link between inflammation and erythropoietin resistance. Conclusions: These observations suggest that sEpoR levels may contribute to erythropoietin resistance in end stage renal disease, and that sEpoR production may be mediated by pro-inflammatory cytokines.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0009246en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821920/pdf/en_US
dash.licenseLAA
dc.subjecthematologyen_US
dc.subjectanemiasen_US
dc.subjectnephrologyen_US
dc.subjectchornic kidney diseaseen_US
dc.subjectdialysis and renal transplantationen_US
dc.titleSoluble Erythropoietin Receptor Contributes to Erythropoietin Resistance in End-Stage Renal Diseaseen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorKarumanchi, Subbian Ananth
dc.date.available2011-05-02T15:56:45Z
dash.affiliation.otherHMS^Medicine- Beth Israel-Deaconessen_US
dash.affiliation.otherHMS^Obstetrics Gynecology and Repro. Bio. - BIDMCen_US
dash.affiliation.otherHMS^Medicine- Beth Israel-Deaconessen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Health Sciences and Technologyen_US
dc.identifier.doi10.1371/journal.pone.0009246*
dash.contributor.affiliatedMutter, Walter
dash.contributor.affiliatedThadhani, Ravi
dash.contributor.affiliatedKhankin, Eliyahu
dash.contributor.affiliatedKarumanchi, Subbian
dash.contributor.affiliatedYuan, Hai-Tao


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record