Monday, August 4, 2008

Gleevec for Nephrogenic Systemic Fibrosis?

Nephrogenic Systemic Fibrosis (NSF) has recently been linked to the gadolinium-based contrast used for MRI imaging in patients with advanced stage (e.g., Stages 4-5) CKD and ESRD. This appears to be most true for the agent gadodiamide (Omniscan) but there are some suggestions that all gadolinium-based agents carry some unacceptably high risk in this patient population.

There is certainly no consensus yet as to how to treat NSF, but things which have been tried and may work in a subset of patients are prednisone, thalidomide, and photopheresis. In addition, a group headed by Rheumatologist Jonathan Kay at Massachusetts General Hospital is initiating a clinical trial using imatinib mesylate (Gleevec) to treat NSF based on some positive responses in a few patients. Gleevec was initially designed to inhibit the tyrosine kinase activity of the bcr-abl gene fusion product which is constitutively active in most forms of chronic myelogenous leukemia (CML). Apparently Gleevec does have some activity against endogenous tyrosine kinases which is postulated to lead to decreased secretion of critical basement membrane components thought to be involved in the fibrotic reaction which occurs in NSF.

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