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J Am Acad Dermatol. 2010 Feb;62(2):343-5. doi: 10.1016/j.jaad.2009.04.022.

Rapid improvement of nephrogenic systemic fibrosis with rapamycin therapy: possible role of phospho-70-ribosomal-S6 kinase.

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  • 1Division of Nephrology, Atlanta Veterans Administration Health Center, Emory University School of Medicine, Atlanta, Georgia, USA. sswaminathan@uams.edu

Abstract

Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder that occurs in some patients with renal insufficiency. Exposure to gadolinium-based contrast agents (GdCA) has been associated with the development of NSF. No uniformly effective treatment options exist. We present immunohistochemical evidence to show that the proliferating fibrocytes of NSF express phospho-70-s6 kinase (PI-3-K), a protein downstream of PI-3-K, and the target of the drug rapamycin. In our patient, use of rapamycin resulted in rapid clinical improvement marked by reduced edema, reduced skin induration, and decreased pain. This suggests a possible role for PI-3-K and rapamycin (mTOR) pathways in the pathogenesis of NSF. Drugs that inhibit these pathways may be a target for future therapy. While our patient did attribute disease onset to GdCA exposure, used on a single occasion for abdominal imaging, he was also exposed to iron, calcium, and darbepoetin alpha at the time of imaging.

Copyright (c) 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

PMID:
20115955
[PubMed - indexed for MEDLINE]
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