Nephrogenic Systemic Fibrosis (NSF) is a disabling dermatologic adverse drug reaction associated with Gadolinium Containing Chelating Agents (GCCAs). Dermatologic adverse drug reactions (dADRs) are important and poorly characterized causes of morbidity and mortality. NSF has been identified in patients with chronic kidney disease (CKD) or acute kidney injury (AKI) who receive GCCAs during Magnetic Resonance Angiograms (MRAs) and Magnetic Resonance Imaging (MRI) procedures. This dADR is manifested by diffuse and localized areas of dural fibrosis and painful flexion contractures, with gadolinium detected in dermis following energy dispersive spectroscopy. Both the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) maintain databases, containing 589 and 104 NSF cases, respectively. Furthermore, the Yale International Registry includes 304 biopsy-proven NSF cases. Additionally, we will access to a database developed by twenty-three product safety law firms who have collated 458 NSF cases, 344 with biopsy confirmation and databases maintained by manufacturers of gadodiamide and gadopentetate dimeglumine contain 340 and 64 cases, respectively. Despite the prevalence of reported NSF cases, this dADR remains poorly characterized and understood. Controversy exists regarding whether NSF is a productspecific or class-related toxicity. This project seeks to demonstrate that a partnership between Research on Adverse Drug Events and Reports (RADAR) program and clinical investigators can allow for a timely and efficient evaluation of this serious dADR by taking innovative approach to combine multiple databases on a product's safety.
The specific aims of this proposal are: 1) To compare the degree of overlap of individual case descriptions in the various data sets and to derive an integrated data set that contains unique cases of NSF culled from the various dataset;and 2) To describe the association of NSF with additional factors such as degree of kidney injury, use of high-doses of erythropoietin, performance of MRA versus MRI procedure, association with hepato-renal syndrome, and acute kidney injury .
Nephrogenic Systemic Fibrosis (NSF) is a disabling dermatologic adverse drug reaction (dADR) associated with Gadolinium Containing Chelating Agents. This serious adverse drug event has not been systematically studied previously. This project seeks to demonstrate that a partnership between pharmacoviligance research and clinical investigators can allow for timely and efficient evaluation of serious dADRs in order to reduce morbidity related to serious dADRs and protect patient safety.
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