BRAF Signaling Pathway Inhibition, Podocyte Injury, and Nephrotic Syndrome.
Am J Kidney Dis
; 70(1): 145-150, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28242136
ABSTRACT
Dabrafenib and trametinib, BRAF and MEK inhibitors, respectively, are effective targeted metastatic melanoma therapies, but little is known about their nephrotoxicity. Although tubulointerstitial injury has been the most widely reported renal side effect of targeted melanoma therapy, nephrotic syndrome has not been reported before. We report on a patient with metastatic melanoma who developed nephrotic syndrome during dabrafenib and trametinib treatment. Kidney biopsy showed diffuse loss of podocyte cytoarchitecture, extensive foot-process effacement, and glomerular endothelial injury. Kidney function and glomerular ultrastructural changes recovered fully after drug withdrawal. In vitro, BRAF inhibition decreased PLCε1 expression in podocytes, accompanied by a reduction in nephrin expression and an increase in permeability to albumin. Additionally, these drugs inhibited the podocyte-vascular endothelial growth factor (VEGF) system. In addition to implications for nephrotic syndrome pathophysiology, we suggest that patients given dabrafenib and trametinib be monitored closely for potential glomerular damage.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oximas
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Piridonas
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Pirimidinonas
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Neoplasias Cutâneas
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Transdução de Sinais
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Proteínas Proto-Oncogênicas B-raf
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Podócitos
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Imidazóis
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Melanoma
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Síndrome Nefrótica
Limite:
Aged
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Female
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Humans
Idioma:
En
Revista:
Am J Kidney Dis
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Itália