Authors
Abstract(s)
A anemia é uma das complicações mais frequentes nos doentes renais crónicos (DRC) em hemodiálise (HD). Esta anemia associa-se a défice de produção de eritropoietina (EPO) a nível renal, e consequente diminuição da produção de eritrócitos. A utilização da terapêutica com eritropoietina humana recombinante (EPOhr) no início dos anos 90 permitiu uma diminuição importante na prevalência de anemia nos DRC, melhorando a função cardíaca e consequentemente a qualidade de vida destes doentes. No entanto, existe uma grande variabilidade na resposta à terapêutica com EPOhr nestes doentes, em que cerca de 25% necessitam de doses elevadas e 5 - 10% não respondem a esta terapêutica. Os mecanismos subjacentes a esta resistência à terapêutica com EPOhr permanecem ainda por elucidar.
Neste trabalho foram estudadas as alterações associadas, com resistência à terapêutica com EPOhr com particular ênfase na inflamação, no metabolismo de ferro e na sua relação com as proteínas morfogénicas ósseas (BPM-2).
Setenta e dois indivíduos portugueses foram incluídos neste estudo: 48 doentes em HD e 24 controlos saudáveis. Treze dos doentes em HD utilizavam Cateter Venoso Central (CVC) e 35 usavam Fístula Artério-Venosa (FAV) como acesso vascular. A todos foi efectuado o hemograma completo, contagem de reticulócitos, e níveis circulantes de transferrina, ferritina, ferro, saturação da transferrina, receptor solúvel da transferrina (RsTf), Proteína C-Reactiva (PCR), interleucina 6 (IL-6) e BMP-2.
Quando comparados com os controlos, os doentes em HD apresentam diminuição na concentração de hemoglobina (Hb), no hematócrito, na contagem de eritrócitos, e na concentração de hemoglobina globular média (CHGM), como também, uma diminuição na contagem do número de reticulócitos, de linfócitos e de plaquetas e nos níveis séricos de ferro e de transferrina. Também foram encontrados em doentes em HD aumento dos níveis de ferritina, RsTf, PCR, IL-6 e BMP-2.
Doentes em HD usando CVC como acesso vascular apresentam um aumento dos níveis séricos de BMP-2, quando comparados com aqueles que utilizam FAV [55,3 (35,8-85,7) e 43,4 (24,9-55,3 pg / mL)], respectivamente. Foram encontradas nos doentes em HD, correlações negativas entre os níveis de BMP-2 e contagem de eritrócitos (r =- 0,390, p = 0,006) e contagem do número de reticulócitos (r =- 0,305, p = 0,033).Os nossos resultados mostram que os níveis de BMP-2 estão aumentados nos doentes em HD, particularmente naqueles que utilizam CVC como acesso vascular. Adicionalmente, o aumento da BMP-2 parece interferir com a eritropoiese. Mais estudos serão necessários para esclarecer o papel da BMP-2 nos distúrbios da eritropoiese e BMP-2 como marcador de doença vascular em doentes em HD.
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
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