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Raloxifene and Bevacizumab for severe complications of hereditary haemorrhagic telangiectasia in a haemodialysis patient.

Morales E, Morales R, Gutiérrez E, Rojas-Rivera J, Praga M - Clin Kidney J (2012)

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology , Instituto de Investigación, Hospital 12 de Octubre, Universidad Complutense de Madrid , Madrid , Spain.

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Mucocutaneous telangiectasias, arteriovenous malformations, epistaxis, gastrointestinal bleeding and iron-deficiency anaemia are the commonest clinical manifestations of HHT... Hepatic involvement, characterized by different arteriovenous malformations within the liver parenchyma, occurs in up to 74% of patients with HHT... Raloxifene increases the expression of endoglin and ALK1, whose synthesis is defective in HHT patients, at the surface of endothelial cells... A remarkable improvement of HHT symptoms along with a significant decrease in the number and severity of epistaxis was observed after raloxifene treatment... Increase of haemodialysis ultrafiltration along with large-volume paracentesis were started, but the patient showed a poor tolerance to these measures, owing to the presence of anaemia, hypotension and chronic liver disease... On the other hand, endoglin and ALK1 are involved in the transforming growth factor-β signalling pathway, which is a potent stimulator of VEFG production... Bevacizumab has been shown to be effective in diseases of abnormal angiogenesis, improving survival and symptomatology... After obtaining the patient's informed consent, six courses of bevacizumab (5 mg/kg) were administered during a 3-month period and raloxifene was maintained without changes... A further reduction in the frequency of epistaxis was observed besides a remarkable improvement of ascites and liver enzymes... As shown in Figure 1, serial CT scans demonstrated a clear diminution of hepatic vascularity and a smooth contour of the liver... Many different therapies have been proposed for epistaxis and hepatic involvement in HHT, but none of them have shown conclusive results... According to our experience, both raloxifene and bevacizumab are very effective alternatives for the treatment of severe HHT in haemodialysis patients... None declared.

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CT scan of the liver with intravenous contrast before and 6 months after bevacizumab treatment, showing a dramatic reduction of vascularity and improvement of liver surface.
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SFS150F1: CT scan of the liver with intravenous contrast before and 6 months after bevacizumab treatment, showing a dramatic reduction of vascularity and improvement of liver surface.

Mentions: We report on a 59-year-old woman with chronic renal failure secondary to bilateral renal hypoplasia and undergoing haemodialysis, who received the diagnosis of HHT. She had presented relapsing epistaxis during the last year, with severe anaemia and hypotension. Due to the need for weekly transfusions and the poor tolerance to haemodialysis sessions, we consider treatment with raloxifene (60 mg/day), a selective estradiol receptor modulator. Raloxifene increases the expression of endoglin and ALK1, whose synthesis is defective in HHT patients, at the surface of endothelial cells [3]. A remarkable improvement of HHT symptoms along with a significant decrease in the number and severity of epistaxis was observed after raloxifene treatment. However, 6 months after the onset of raloxifene treatment, the patient presented with signs and symptoms of high-output cardiac failure, with severe ascites and a left pleural effusion. Increase of haemodialysis ultrafiltration along with large-volume paracentesis were started, but the patient showed a poor tolerance to these measures, owing to the presence of anaemia, hypotension and chronic liver disease. Serum biochemistry demonstrated a progressive cholestasis. A computed tomography (CT) scan showed liver cirrhosis with splenomegaly and massive arteriovenous malformations (Figure 1). Prompted by the progressive clinical deterioration of the patient, we decided to start treatment with bevacizumab, a humanized recombinant monoclonal antibody against the vascular endothelial growth factor (VEFG). The VEGF is a key regulator of angiogenesis and is upregulated in a variety of diseases. On the other hand, endoglin and ALK1 are involved in the transforming growth factor-β signalling pathway, which is a potent stimulator of VEFG production. Bevacizumab has been shown to be effective in diseases of abnormal angiogenesis, improving survival and symptomatology [4, 5]. Bevacizumab has been also used for the treatment of liver complications of HHT, inducing a clear improvement [6]. After obtaining the patient's informed consent, six courses of bevacizumab (5 mg/kg) were administered during a 3-month period and raloxifene was maintained without changes. A further reduction in the frequency of epistaxis was observed besides a remarkable improvement of ascites and liver enzymes. As shown in Figure 1, serial CT scans demonstrated a clear diminution of hepatic vascularity and a smooth contour of the liver.Fig. 1.


Raloxifene and Bevacizumab for severe complications of hereditary haemorrhagic telangiectasia in a haemodialysis patient.

Morales E, Morales R, Gutiérrez E, Rojas-Rivera J, Praga M - Clin Kidney J (2012)

CT scan of the liver with intravenous contrast before and 6 months after bevacizumab treatment, showing a dramatic reduction of vascularity and improvement of liver surface.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400569&req=5

SFS150F1: CT scan of the liver with intravenous contrast before and 6 months after bevacizumab treatment, showing a dramatic reduction of vascularity and improvement of liver surface.
Mentions: We report on a 59-year-old woman with chronic renal failure secondary to bilateral renal hypoplasia and undergoing haemodialysis, who received the diagnosis of HHT. She had presented relapsing epistaxis during the last year, with severe anaemia and hypotension. Due to the need for weekly transfusions and the poor tolerance to haemodialysis sessions, we consider treatment with raloxifene (60 mg/day), a selective estradiol receptor modulator. Raloxifene increases the expression of endoglin and ALK1, whose synthesis is defective in HHT patients, at the surface of endothelial cells [3]. A remarkable improvement of HHT symptoms along with a significant decrease in the number and severity of epistaxis was observed after raloxifene treatment. However, 6 months after the onset of raloxifene treatment, the patient presented with signs and symptoms of high-output cardiac failure, with severe ascites and a left pleural effusion. Increase of haemodialysis ultrafiltration along with large-volume paracentesis were started, but the patient showed a poor tolerance to these measures, owing to the presence of anaemia, hypotension and chronic liver disease. Serum biochemistry demonstrated a progressive cholestasis. A computed tomography (CT) scan showed liver cirrhosis with splenomegaly and massive arteriovenous malformations (Figure 1). Prompted by the progressive clinical deterioration of the patient, we decided to start treatment with bevacizumab, a humanized recombinant monoclonal antibody against the vascular endothelial growth factor (VEFG). The VEGF is a key regulator of angiogenesis and is upregulated in a variety of diseases. On the other hand, endoglin and ALK1 are involved in the transforming growth factor-β signalling pathway, which is a potent stimulator of VEFG production. Bevacizumab has been shown to be effective in diseases of abnormal angiogenesis, improving survival and symptomatology [4, 5]. Bevacizumab has been also used for the treatment of liver complications of HHT, inducing a clear improvement [6]. After obtaining the patient's informed consent, six courses of bevacizumab (5 mg/kg) were administered during a 3-month period and raloxifene was maintained without changes. A further reduction in the frequency of epistaxis was observed besides a remarkable improvement of ascites and liver enzymes. As shown in Figure 1, serial CT scans demonstrated a clear diminution of hepatic vascularity and a smooth contour of the liver.Fig. 1.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology , Instituto de Investigación, Hospital 12 de Octubre, Universidad Complutense de Madrid , Madrid , Spain.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Mucocutaneous telangiectasias, arteriovenous malformations, epistaxis, gastrointestinal bleeding and iron-deficiency anaemia are the commonest clinical manifestations of HHT... Hepatic involvement, characterized by different arteriovenous malformations within the liver parenchyma, occurs in up to 74% of patients with HHT... Raloxifene increases the expression of endoglin and ALK1, whose synthesis is defective in HHT patients, at the surface of endothelial cells... A remarkable improvement of HHT symptoms along with a significant decrease in the number and severity of epistaxis was observed after raloxifene treatment... Increase of haemodialysis ultrafiltration along with large-volume paracentesis were started, but the patient showed a poor tolerance to these measures, owing to the presence of anaemia, hypotension and chronic liver disease... On the other hand, endoglin and ALK1 are involved in the transforming growth factor-β signalling pathway, which is a potent stimulator of VEFG production... Bevacizumab has been shown to be effective in diseases of abnormal angiogenesis, improving survival and symptomatology... After obtaining the patient's informed consent, six courses of bevacizumab (5 mg/kg) were administered during a 3-month period and raloxifene was maintained without changes... A further reduction in the frequency of epistaxis was observed besides a remarkable improvement of ascites and liver enzymes... As shown in Figure 1, serial CT scans demonstrated a clear diminution of hepatic vascularity and a smooth contour of the liver... Many different therapies have been proposed for epistaxis and hepatic involvement in HHT, but none of them have shown conclusive results... According to our experience, both raloxifene and bevacizumab are very effective alternatives for the treatment of severe HHT in haemodialysis patients... None declared.

No MeSH data available.