کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5685473 | 1598224 | 2017 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
BRAF Signaling Pathway Inhibition, Podocyte Injury, and Nephrotic Syndrome
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کلمات کلیدی
DabrafenibPodocyte injury - آسیب دیدگیRenal biopsy - بیوپسی کلیویTrametinib - ترماتینیبMelanoma - خال سرطانی یا ملانوماTargeted cancer therapy - درمان سرطان هدفمندnephrotic syndrome - سندرم نفروتیکMEK inhibitor - مهار کننده MEKBRAF inhibitor - مهارکننده BRAFNephrotoxicity - نفخ سمیProteinuria - پروتئینوریCase report - گزارش موردیglomerulopathy - گلومرولوپاتی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: American Journal of Kidney Diseases - Volume 70, Issue 1, July 2017, Pages 145-150
Journal: American Journal of Kidney Diseases - Volume 70, Issue 1, July 2017, Pages 145-150
نویسندگان
Luca PhD, Mario MD, Arrigo MD, Camillo MD, Paola PhD, Sara BSc, Lorena BiolSciD, Ariela PhD, Giuseppe MD, FRCP,