Transglutaminases seen as 'missing link' in nephrogenic systemic fibrosis

-Medicexchange

10/19/2007 - Transglutaminases are upregulated in nephrogenic systemic fibrosis (NSF), a condition that can occur in renal failure patients after gadolinium contrast exposure, according to a report in the October issue of the American Journal of Dermatopathology.

"Our preliminary studies have identified a potential molecular mechanism for NSF," Dr. David C. Sane told Reuters Health. "Our hope is that this finding will lead to therapy (a transglutaminase inhibitor) that could prevent NSF from occurring."

Dr. Sane from Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, and associates examined skin biopsies from five NSF patients to test their hypothesis that upregulation of transglutaminases contributes to the fibrosis seen in this condition.

Transglutaminases were readily observed in the spindle cells and histiocytes of all cases of NSF but weakly or not at all in the spindle cells of normal skin, the researchers report.

Skin biopsies from NSF patients and from normal controls all showed strong reactivity to the histiocyte marker CD68 by spindle cells and histiocytes in the dermis and subcutaneous tissue, the report indicates, whereas there was rare staining of dermal histiocytes in normal skin controls.

"Our studies may lead to an understanding of the pathophysiology behind this disease," Dr. Sane said.

"An important point for the practicing physician is that NSF is a devastating iatrogenic disease that is preventable, at least in the majority of cases, by avoiding the use of gadolinium-based contrast agents in patients with significant renal dysfunction," Dr. Sane added.


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