We observed the following biological changes in the skin and dermal fibroblasts of both healthy and ESRD subjects after exposure to Omniscan:

• Skin from healthy and ESRD subjects responded to Omniscan exposure with an increase in MMP-1, TIMP-1 and Hyaluronan production.
• We found that the skin of ESRD subjects has a higher basal level of MMP-1 and TIMP-1 when compared to that of healthy subjects.
• Histological analysis with Alcian blue stain and hyaluronidase digestion re-affirmed the increased production of hyaluronan in response to Omniscan exposure in both healthy and ESRD subjects.
• The analysis of procollagen type I in ESRD subjects showed no increase in procollagen type I when exposed to Omniscan. This is consistent with our previous findings(1).
• Fibroblasts isolated from both healthy and ESRD skin biopsies responded to Omniscan in a similar way with an increase in the production of MMP-1, TIMP-1 and hyaluronan.
• Fibroblasts isolated from the skin of  ESRD and healthy subjects have similar basal levels of MMP-1, TIMP-1 and hyaluronan unlike whole skin biopsy punches.

What accounts for elevated basal levels in the skin from ESRD subjects is not fully understood at this time. Both our previous and current work suggest that fibroblasts are a direct target of GBCAs. However, they may be both an indirect and direct target. 

Patients in renal failure are susceptible to a number of inflammatory skin complications and many of these have a fibrosing component (6-9). Alterations in an enzyme / inhibitor system responsible for matrix turn-over in the skin, as well as alterations in the level of at least one matrix component may contribute to the pathophysiology of some of these conditions. Additional work will need to be done to make more solid conclusions regarding our observations and their role in the pathophysiology of NSF.