This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Nephrotic systemic fibrosis (NSF) is a debilitating, painful, often fatal disease. It is associated with renal insufficiency and exposure to gadolinium-based magnetic resonance imaging contrast agents. Symptoms include the presence of insoluble Gadolinium deposits in the skin. It is believed that these deposits may play a key role in the NSF disease. However, their chemical composition is currently unclear. Resolving this is clearly important for a proper understanding of the disease. We have previously characterized a fixed autopsy tissue sample using micro XAS imaging, x-ray tomography and EXAFS spectroscopy. These results show a distribution of Gd:Ca:P particles with a structure based on gadolinium phosphate. This work has been submitted for publication. We plan to extend these studies to fixed and frozen tissue samples from several different patients and from the same patient at different times. This will also us to characterize detailed differences and changes in the structure of the Gd deposits with different patients and with an individual patient?s disease status. Comparisons of fixed and frozen tissues will confirm whether the process of fixing the tissue has chemically modified the deposits. Frozen tissue samples will also allow study the chemical nature of any Gd outside the insoluble deposits.
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