Anemia is one of the most common complications in patients with Chronic Kidney Disease (CKD) on hemodialysis (HD). This anemia is associated with insufficient synthesis of erythropoietin (EPO) by the kidneys, causing a decrease in the production of red blood cells. The use of therapy with recombinant human erythropoietin (EPOhr) in the early 90's allowed a significant decrease in the prevalence of anemia in patients with CKD, significantly saving transfusion requirements. This therapy allowed an improvement of cardiac function and improving the quality of life of these patients. However, there is great variability in response to therapy EPOhr. About 25% of patients need high doses and 50-10% does not respond to EPOhr therapy. The mechanisms underlying resistance to EPOhr therapy remain controversial. In this study, we evaluated associated specific alterations with particular emphasis in inflammation, iron metabolism parameters and their relation to bone morphogenetic proteins (BMP-2), in order to clarify the mechanisms of resistance to therapy EPOhr therapy of CDK patients in HD. Seventy-three Portuguese individuals were enrolled in this study: 48 HD patients and 25 healthy controls. Fourteen HD patients used central venous catheter (CVC) and 34 arterio-venous fistula (AVF) as vascular access. Complete blood count, reticulocyte count, and circulating levels of transferrin, ferritin, iron, transferrin saturation, soluble transferrin receptor (s-TfR), C-reactive protein (CRP), interleukin 6 (IL-6) and BMP-2, were evaluated for all patients and controls. When compared to healthy controls, HD patients showed significantly lower haemoglobin concentration, haematocrit, red blood cell counts and mean cell haemoglobin concentration; iron and tranferrin serum levels, reticulocyte, lymphocytes and platelets counts. Increased mean cell haemoglobin, ferritin, TfR, CRP, IL-6 and BMP-2 were also found in HD patients. HD patients using CVC as vascular access presented an increased BMP-2 serum levels, when compared with those using AVF [55,3 (35,8-85,7) and 43,4 (24,9-55,3 pg/mL), respectively]. In HD patients, negative correlations were found between BMP-2 serum levels, and erythrocyte (r=-0,390; p=0,006) and reticulocyte counts (r=-0,305; p=0,033). Our data show that BMP-2 is increased HD patients, particularly in those using CVC access for HD procedure; moreover, the rise in BMP-2 seems to negatively interfere with erythropoiesis. Further studies are needed to clarify the role of BMP-2 in the eryhropoietic disturbances and to study BMP-2 as a marker of vascular disease in HD patients, as it might provide a potential target to slow-down the accelerated course of HD associated vascular disease
Date of Award | Nov 2011 |
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Original language | Portuguese |
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Awarding Institution | - Universidade Católica Portuguesa
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Supervisor | Maria Alice dos Santos Silva G. Martins (Supervisor) & Elísio Manuel de Sousa Costa (Co-Supervisor) |
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- Mestrado em Análises Clínicas e Saúde Pública
Resistência à terapêutica com eritropoietina humana recombinante e níveis plasmáticos de BMP 2 em doentes hemodialisados
Coimbra, J. L. M. (Student). Nov 2011
Student thesis: Master's Thesis