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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Ribeiro, S (Autor) Outra; Garrido, P (Autor) Outra; Fernandes, J (Autor) Outra; Vala, H (Autor) Outra; Rocha Pereira, P (Autor) Outra; Costa, E (Autor) FFUP; Belo, L (Autor) FFUP; Reis, F (Autor) Outra; Alice Santos Silva (Autor) FFUP

Revista

Título: Clinical And Experimental Pharmacology And Physiology

Vol. 43

Páginas: 343-354

ISSN: 0305-1870

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 7 Citações

Scopus - 7 Citações

Outras Informações

ID Authenticus: P-00K-7Q1

DOI: 10.1111/1440-1681.12541

Abstract (EN): Clinical 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, 200IU/kg body weight (BW) per week) and in higher doses used in the treatment of hyporesponsive patients (400, 600IU/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 rHuEPO-treated 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12