Transglutaminases: The missing link in nephrogenic systemic fibrosis

Amy C. Parsons, Gil Yosipovitch, Daniel J. Sheehan, Omar P. Sangüeza, Charles S. Greenberg, David C. Sane

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy (NFD), occurs in renal failure patients after gadolinium contrast exposure. The fibrosis of the dermis and subcutaneous septae accompanies fibrosis of other organs, including the heart, liver, lungs, and muscle. The fibrotic skin demonstrates increased dermal collagen, fibroblasts, and mucin. The mechanism by which gadolinium is associated with fibrosis is not known.We tested the hypothesis that upregulation of transglutaminases contributes to the fibrosis seen in the organs, including skin, of renal failure patients exposed to gadolinium contrast.We performed immunohistochemical studies using antibodies to transglutaminase-2, factor XIIIa, transglutaminase isopeptide, and the histiocyte marker CD68 on five archived skin biopsies of NSF. The results indicate that the dermal fibroblasts and histiocytes of NSF express transglutaminase-2, CD68, factor XIIIa, and transglutaminase isopeptide, indicating increased expression and/or activation of transglutaminases in NSF. We recommend further research into the use of transglutaminase inhibitors in the treatment and prevention of NSF.

Original languageEnglish (US)
Pages (from-to)433-436
Number of pages4
JournalAmerican Journal of Dermatopathology
Issue number5
StatePublished - Oct 2007
Externally publishedYes


  • Gadolinium
  • Nephrogenic fibrosing dermopathy
  • Nephrogenic systemic fibrosis
  • Renal failure
  • Transglutaminase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Dermatology


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