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Renal risk-benefit determinants of recombinant human erythropoietin therapy in the remnant kidney rat model - hypertension, anaemia, inflammation and drug dose.

2016-03Journal article Restricted access
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dc.contributor.authorRibeiro, Sandra
dc.contributor.authorGarrido, Patrícia
dc.contributor.authorFernandes, João
dc.contributor.authorVala, Helena
dc.contributor.authorRocha-Pereira, Petronila
dc.contributor.authorCosta, Elísio
dc.contributor.authorBelo, Luís
dc.contributor.authorReis, Flávio
dc.contributor.authorSantos-Silva, Alice
dc.date.accessioned2020-03-05T11:03:12Z
dc.date.available2020-03-05T11:03:12Z
dc.date.issued2016-03
dc.date.updated2020-03-03T14:56:37Z
dc.description.abstractClinical studies showed that high doses of recombinant human erythropoietin (rHuEPO) used to correct anaemia in chronic kidney disease (CKD) hyporesponsive patients may lead to deleterious effects. The aim of this study was to analyze the effects of rHuEPO in doses usually used to correct CKD-anaemia (100, 200 IU/kg body weight (BW) per week) and in higher doses used in the treatment of hyporesponsive patients (400, 600 IU/kg BW per week), focusing on renal damage, hypoxia, inflammation and fibrosis. Male Wistar rats with chronic renal failure (CRF) induced by 5/6 nephrectomy were treated with rHuEPO or with vehicle, over a 3-week period. Haematological, biochemical and renal function analyses were performed. Kidney and liver mRNA levels were evaluated by quantitative real-time polymerase chain reaction (qPCR) and protein expression by Western blot and immunohistochemistry. Kidney histopathological evaluations were also performed. The CRF group developed anaemia, hypertension and a high score of renal histopathologic lesions. Correction of anaemia was achieved with all rHuEPO doses, with improvement in hypertension, renal function and renal lesions. In addition, the higher rHuEPO doses also improved inflammation. Blood pressure was reduced in all rHuEPOtreated groups, compared to the CRF group, but increased in a dose-dependent manner. The current study showed that rHuEPO treatment corrected anaemia and improved urinary albumin excretion, particularly at lower doses. In addition, it is suggested that a short-term treatment with high doses, used to overcome an episode of hyporesponsiveness to rHuEPO therapy, can present benefits by reducing inflammation, without worsening of renal lesions; however, the pro-hypertensive effect should be considered, and carefully managed to avoid a negative cardiorenal impact.pt_PT
dc.description.versionN/Apt_PT
dc.identifier.doi10.1111/1440-1681.12541pt_PT
dc.identifier.pmid26889660
dc.identifier.slugcv-prod-589326
dc.identifier.urihttp://hdl.handle.net/10400.19/6229
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectanaemiapt_PT
dc.subjecthigh rHuEPO dosespt_PT
dc.subjecthypertensionpt_PT
dc.subjecthyporesponsivenesspt_PT
dc.subjectinflammationpt_PT
dc.titleRenal risk-benefit determinants of recombinant human erythropoietin therapy in the remnant kidney rat model - hypertension, anaemia, inflammation and drug dose.pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleClinical and Experimental Pharmacology and Physiologypt_PT
oaire.citation.volume43pt_PT
person.familyNameVala Correia
person.givenNameHelena Maria
person.identifier.ciencia-id7A1E-E85E-FFA4
person.identifier.orcid0000-0001-6829-4867
rcaap.cv.cienciaid7A1E-E85E-FFA4 | Helena Maria Vala Correia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationcdc3d2e2-df06-40ed-8900-1ecbc8a06c8a
relation.isAuthorOfPublication.latestForDiscoverycdc3d2e2-df06-40ed-8900-1ecbc8a06c8a

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