Rapid improvement of nephrogenic systemic fibrosis with rapamycin therapy: possible role of phospho-70-ribosomal-S6 kinase.
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.
Swaminathan
Sundararaman
S
Division of Nephrology, Atlanta Veterans Administration Health Center, Emory University School of Medicine, Atlanta, Georgia, USA. sswaminathan@uams.edu
Arbiser
Jack L
JL
Hiatt
Kim M
KM
High
Whitney
W
Abul-Ezz
Sameh
S
Horn
Thomas D
TD
Shah
Sudhir V
SV
D003287:Contrast Media / Q000009:adverse effects; D019786:Gadolinium DTPA / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D054989:Nephrogenic Fibrosing Dermopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D020123:Sirolimus / Q000627:therapeutic use*
D003287:Contrast Media; C064925:gadodiamide; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D019786:Gadolinium DTPA; D020123:Sirolimus