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Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia

2016Journal article Open access
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dc.contributor.authorGarrido, Patrícia
dc.contributor.authorRibeiro, Sandra
dc.contributor.authorFernandes, João
dc.contributor.authorVala, Helena
dc.contributor.authorRocha-Pereira, Petronila
dc.contributor.authorBronze-da-Rocha, Elsa
dc.contributor.authorBelo, Luís
dc.contributor.authorCosta, Elísio
dc.contributor.authorSantos-Silva, Alice
dc.contributor.authorReis, Flávio
dc.date.accessioned2016-02-15T14:41:53Z
dc.date.available2016-02-15T14:41:53Z
dc.date.issued2016
dc.description.abstractThis study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy.pt_PT
dc.identifier.citationGarrido P, Ribeiro S, Fernandes J, Vala H, Rocha-Pereira P,Bronze da Rocha E,Belo L, Costa E,Santos-Silva A, Reis F (2016). Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia. International Journal of Molecular Sciences, 17, 28:1-28pt_PT
dc.identifier.doi10.3390/ijms17010028pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.19/3058
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationThis study was supported by grants from the Portuguese Foundation for Science and Technology (FCT) and COMPETE: PTDC/SAU-TOX/114253/2009, SFRH/BD/61020/2009, SFRH/BD/79875/2011, SFRH/BPD/81968/2011, Pest/C/SAU/3282/2011 and 2013 (IBILI), PEst-OE/CED/UI4016/2014 (CI&DETS), UID/AGR/04033 and UID/NEU/04539/2013 (CNC.IBILI), IPV, CITAB and QREN/FEDER (Ovislab ICT-2013-05-004-5314 ID-64757)pt_PT
dc.subjectchronic kidney diseasept_PT
dc.subjectanemiapt_PT
dc.subjectremnant kidney rat modelpt_PT
dc.subjectresistance to rHuEPO therapy erythropoiesispt_PT
dc.subjectinflammation and fibrosispt_PT
dc.subjectkidney hypoxiapt_PT
dc.subjectiron metabolismpt_PT
dc.titleResistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage28pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume17pt_PT
person.familyNameVala Correia
person.givenNameHelena Maria
person.identifier.ciencia-id7A1E-E85E-FFA4
person.identifier.orcid0000-0001-6829-4867
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationcdc3d2e2-df06-40ed-8900-1ecbc8a06c8a
relation.isAuthorOfPublication.latestForDiscoverycdc3d2e2-df06-40ed-8900-1ecbc8a06c8a

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