Unexpected Complicaons of Gadolinium-Based Contrast Agents: Nanoparcles Formaon and Profound Perturbaon of Metabolism Victor Andujo 1 , Patricia Escobar 1,2 and Brent Wagner 1,2,3* 1 University of New Mexico School of Medicine, Albuquerque, New Mexico, USA 2 Kidney Instute of New Mexico, Albuquerque, New Mexico, USA 3 New Mexico Veterans Administraon Health Care System, Albuquerque, New Mexico, USA * Corresponding author: Wagner B, Director, Kidney Instute of New Mexico, Albuquerque, New Mexico, USA, Tel: 5059251025; E-mail: BrWagner@salud.unm.edu Received: May 15, 2019; Accepted: May 22, 2019; Published: March 29, 2019 Copyright: © 2019 Andujo V, et al. This is an open-access arcle distributed under the terms of the Creave Commons Aribuon License, which permits unrestricted use, distribuon, and reproducon in any medium, provided the original author and source are credited. Abstract Gadolinium-induced systemic fibrosis was inially recognized in paents with end stage renal disease (with funconing renal transplants or on chronic hemodialysis) and acute kidney injury. Despite a ‘ black box ’ warning against the use of all gadolinium-based agents in anyone with renal insufficiency, such paents are sll subjected to gadolinium contrast-enhanced imaging when the diagnosc informaon is thought to outweigh the risks. The odds rao for paents with end-stage renal disease contracng gadolinium induced systemic fibrosis aſter an exposure to gadolinium-based contrast ranges from 20.6 to 41.3. The mechanism of how gadolinium induces systemic fibrosis is central to this review. Our research validates the finding that gadolinium-based contrast agents have effects on renal histology and kidney funcon. Using lethally-irradiated rats salvaged with tagged bone marrow, we provided experimental evidence that over 40% of the cellularity of gadolinium-induced fibroc lesions originated from circulang fibrocytes. Through this model we demonstrated that gadolinium-based contrast treatment leads to gadolinium deposion in the skin, histologic features of fibrosis, an increase in dermal cellularity (predominantly of the spindle-type cells similar to what has been described in paents with gadolinium-induced systemic fibrosis), and measurable markers of fibrosis. In a mouse model, we discovered that gadolinium-based contrast agent treatment led to amorphous mesh-like nanowire structures found in mulnucleated giant cells of the skin and the renal proximal tubules. Our data indicate gadolinium concentrates in the kidney and induces glomerular pathology. Progression on idenfying triggering mechanisms of gadolinium-induced systemic fibrosis will assist in unraveling the process of disease iniaon and guide raonal approaches for prophylaxis and treatment. Keywords: Nephrogenic systemic fibrosis; Gadolinium; Nanoparcles; Metabolism Introducon Magnec resonance imaging has revoluonized diagnosc medicine. Six million doses of gadolinium-based contrast are administered annually [1,2]. Approximately 50,000 MRI examinaons are conducted world-wide every day, tallying more than 40 million procedures annually. In 1997, a painful and severely debilitang disease was recognized in paents with end-stage renal disease (with funconing renal transplants or on chronic hemodialysis) and acute kidney injury. In 2006, it was realized that this syndrome, misnamed ‘nephrogenic’ systemic fibrosis1, was caused by gadolinium-based contrast agents. Gadolinium-induced systemic fibrosis is a ghastly disorder. The odds rao for paents with end-stage renal disease contracng it aſter an exposure to gadolinium based contrast ranges from 20.6 to 41.3 [1]. Paents with chronic and end-stage renal disease sll are at risk for exposure to high-risk gadolinium- based contrast agents (despite the FDA “black box” warning) [3]. Despite a ‘black box’ warning against the use of all gadolinium- based agents in anyone with renal insufficiency, such paents are sll subjected to gadolinium contrast enhanced imaging when the diagnosc informaon is thought to outweigh the risks. Thousands of hemodialysis paents, 405 peritoneal dialysis paents, and over 1000 severe chronic kidney disease paents were exposed to MulHance, (a gadolinium-based contrast agent) at the University of Arizona College of Medicine, Banner University Medical Center in Tucson despite the United States Food & Drug Administraon boxed warning about these high-risk populaons. This paper was rapidly withdrawn by the authors, cing “the study was not conducted in full accordance with the relevant instuonal IRB protocol.” The United States Food & Drug Administraon Adverse Events Reporng System (FAERS) Public Dashboard lists 574 cases of gadolinium-induced systemic fibrosis under “ MulHance ” alone as of this wring and over 3,000 cases when all gadolinium-based contrast agents are included in the search. Gadolinium-based contrast remains a mainstay of diagnosc imaging and alternaves are lacking. Even in academic centers (such as the University of Arizona) thousands of high-risk paents with chronic or acute kidney impairment connue to be exposed to gadolinium-based Review Article iMedPub Journals http://www.imedpub.com/ Journal of Clinical & Experimental Nephrology ISSN 2472-5056 Vol.4 No.2:1 2019 © Under License of Creative Commons Attribution 3.0 License | This article is available from: http://clinical-experimental-nephrology.imedpub.com/ 1