Incidence of Nephrogenic Systemic Fibrosis in Patients Undergoing Dialysis After Contrast-Enhanced Magnetic Resonance Imaging With Gadolinium-Based Contrast Agents The Prospective Fibrose Nephroge ´nique Syste ´mique Study Sabine Amet, PharmD,* Vincent Launay-Vacher, PharmD,* Olivier Cle ´ment, MD, PhD,Þ Camille Frances, MD,þ Aurore Tricotel, MSc,§ Benedicte Stengel, MD,|| Jean-Yves Gauvrit, MD,¶ Nicolas Grenier, MD,# Genevie `ve Reinhardt, MD,** Nicolas Janus, PharmD,* Gabriel Choukroun, MD,ÞÞ Maurice Laville, MD,þþ and Gilbert Deray, MD§§ Background: Nephrogenic systemic fibrosis (NSF) has been related to the use of gadolinium-based contrast agents (GBCAs) in patients undergoing dialysis. The Prospective Fibrose Nephroge ´nique Syste ´mique study, a French prospective study supported by the French drug regulatory agency (Agence Nationale de Se ´curite ´ du Me ´dicament) and the French Societies of Nephrology, Dermatology, and Radiology, aimed at determining the incidence of NSF in patients undergo- ing long-term dialysis. Materials and Methods: Adult patients undergoing long-term dialysis re- ceiving a magnetic resonance imaging (MRI) examination prescribed between January 15, 2009 and May 31, 2011, with or without GBCA were included. The methodology was based on a patient form intended to detect any dermatological event (DE) that may occur within 4 months after the examination. Further in- vestigations were planned with their physicians if a DE was reported. Results: A total of 571 patients were included. A total of 50.3% received GBCA. Among them, 93.4% received a macrocyclic GBCA, usually gadoteric acid (88.9%). All in all, 22 patients (3.9%) reported a DE. Dermatological diagnoses did not reveal any evidence of NSF. Conclusions: The incidence of NSF after a single dose of a macrocyclic GBCA is null in our sample of 268 patients undergoing dialysis (hemodialysis and peritoneal dialysis). This incidence is just lower than 0.5%. When contrast- enhanced MRI can be essential, or even decisive, to the diagnosis, these results are important and reassuring if physicians need to perform contrast-enhanced MRI in patients undergoing dialysis. Key Words: nephrogenic systemic fibrosis, end-stage renal disease, dialysis, magnetic resonance imaging, gadolinium-based contrast agents, macrocyclic agents, gadoteric acid (Invest Radiol 2013;00: 00Y00) N ephrogenic systemic fibrosis (NSF) is a diffuse fibrosis of tissue disorder in the setting of advanced renal dysfunction. First de- scribed as a scleromyxedema-like cutaneous disease in patients un- dergoing renal dialysis in 2000, it was later termed nephrogenic fibrosing dermopathy . 1,2 With some reports of systemic lesions such as cardiomyopathy, pulmonary fibrosis, or diaphragmatic paralysis, this entity was appropriately renamed NSF . 3Y6 Approximately 380 cases were reported to the NSF registry at Yale University and more than 700 cases worldwide in patients with renal impairment (RI). 7Y9 Renal impairment is thus the major risk factor for NSF. Indeed, 79% of cases were reported in patients with end-stage renal disease (ESRD) on dialysis. Nephrogenic systemic fibrosis was also de- scribed in patients with acute kidney injury (10%), stage 4 chronic kidney disease (8%), and failed renal transplants (3%). 10 Although the pathogenesis of NSF is thought to be multifac- torial, nearly all known cases of NSF were reported in patients with prior exposure to gadolinium contrast-enhanced magnetic resonance imaging (CE-MRI) within 2 to 3 months of symptom onset, sug- gesting this class of drugs as a possible trigger. 11Y14 In 2011, an ac- curate method to diagnose NSF with a clinicopathological score that correlates the clinical manifestations to the histological results of the skin biopsy was developed by a group of experts convened by the American College of Radiology. 15 The prevalence of NSF in patients with RI depends on which gadolinium-based contrast agents (GBCAs) is used. 16,17 According to the literature, gadodiamide is the most involved product. 18Y22 The European Symposium on Urogenital Radiology reported that the prevalence of NSF after exposure to a linear GBCA (gadodiamide) was ranging from 3% to 7% in patients with reduced renal function (glomerular filtration rate [GFR], less than 30 mL/min per 1.73 m 2 ). 23 In patients undergoing dialysis, the prevalence reported seems to be higher but still depends on the thermodynamic stability of the GBCA used. The prevalence of NSF is 18% after exposure to 0.2 mmol/kg of gadodiamide in patients with ESRD (GFR less than 15 mL/min per 1.73 m 2 ). 24 In this group of patients with ESRD, the patients on regular dialysis therapy (hemodialysis [HD] or peritoneal dialysis [PD]) at GBCA exposure and the patients with more than 1 GBCA ex- posure in their lifetime had the highest prevalence of NSF. 24 Since 2006, a total of 9 studies aimed at determining the prevalence of NFS in patients undergoing dialysis. 25Y33 In the 6 studies reported on patients undergoing dialysis who were exposed to linear GBCA only (gadodiamide or gadopentetate dimeglumine), the prevalence ranges from 1.5% to 29.6%. In the 2 studies performed in patients undergoing dialysis who were exposed to linear and macrocyclic GBCA, the prevalence ranges from 0.4% to 1.6%. 25Y33 One of them performed in 1096 patients reported a prevalence of 0.7%: 2.6% of cases identified in the 312 patients who received gadodiamide and none ORIGINAL ARTICLE Investigative Radiology & Volume 00, Number 00, Month 2013 www.investigativeradiology.com 1 Received for publication April 30, 2013; and accepted for publication, after revision, August 20, 2013. From the *Service Information Conseil Adaptation Re ´nale, Department of Nephrology, Ho ˆpital Pitie ´-Salpe ˆtrie `re; †Department of Radiology, Ho ˆpital Europe ´en Georges Pompidou; ‡Department of Dermatology, Ho ˆpital Tenon, Paris; §Department of Pharmacovigilance, Agence Nationale de Se ´curite ´ du Me ´dicament, Saint-Denis; ||Department of Inserm U1018, Ho ˆpital Paul Brousse, Villejuif; ¶Department of Radiology, Ho ˆpital Pontchaillou, Rennes; #Department of Radiology, Ho ˆpital Pellegrin, Bordeaux; **Department of Radiology, Ho ˆpital d’Haguenau, Haguenau; ††Department of Nephrology Dialysis and Transplan- tation and INSERM 1088, Ho ˆpital Sud, Amiens; ‡‡Department of Nephrology, Ho ˆpital Lyon Sud, Lyon; and §§Department of Nephrology, Ho ˆpital Pitie ´- Salpe ˆtrie `re, Paris, France. Conflicts of interest and sources of funding: none declared. Reprints: Sabine Amet, PharmD, Service Information Conseil Adaptation Re ´nale, Department of Nephrology, Ho ˆpital Pitie ´-Salpe ˆtrie `re, 83 Boulevard de l’Ho ˆpital, 75013 Paris, France. E-mail: sabine.amet@psl.aphp.fr. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0020-9996/00/0000Y0000 Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.