Abstract
Purpose
To update the guidelines of the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic fibrosis and gadolinium-based contrast media.
Areas covered
Topics reviewed include the history, clinical features and prevalence of nephrogenic systemic fibrosis and the current understanding of its pathophysiology. The risk factors for NSF are discussed and prophylactic measures are recommended. The stability of the different gadolinium-based contrast media and the potential long-term effects of gadolinium in the body have also been reviewed.
Key Points
• Clinical features, risk factors and prevention of nephrogenic systemic fibrosis are reviewed
• Patients with GFR below 30 ml/min/1.73 m 2 have increased risk of developing NSF
• Low stability gadolinium contrast media show the strongest association with NSF
• Following guidelines regarding gadolinium contrast agents minimises the risk of NSF
• Potential long-term harm from gadolinium accumulation in the body is discussed
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References
Thomsen HS (2007) ESUR guideline: gadolinium-based contrast media and nephrogenic systemic fibrosis. Eur Radiol 17:2692–2696
Stacul F, van der Molen AJ, Reimer P, Webb JAW, Thomsen HS, Morcos SK, Almén T, Aspelin P, Bellin M-F, Clement O, Heinz-Peer G; Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) (2011) Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 21:2527–2541
Prince MR, Arnoldus C, Frisoli JK (1996) Nephrotoxicity of high-dose gadolinium compared with iodinated contrast. JMRI 1:162–166
Thomsen HS, Almén T, Morcos SK; Contrast Media Safety Committee of the European Society of Urogenital Radiology (2002) Gadolinium-containing contrast media for radiographic examinations: a position paper. Eur Radiol 12:2600–2605
Gemmette JJ, Forauer AR, Kazanijan S, Dasika N, Williams DM, Cho K (2001) Safety of large volume gadolinium angiography. J Vasc Interv Radiol 12(Part 2):S28
Cowper SE, Robin HS, Steinberg SM et al (2000) Scleromyxoedema-like cutaneous disease in renal dialysis patients. Lancet 356:1000–1001
Grobner T (2006) Gadolinium: a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis. Nephrol Dial Transplant 21:1104–1108
Marckmann P, Skov L, Rossen K et al (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362
Thomsen HS, Marckmann P (2008) Extracellular Gd-CM: Differences in prevalence of NSF. Eur J Radiol 66:180–183
Thomsen HS (2009) Delayed reactions: nephrogenic systemic fibrosis. In: Thomsen HS, Webb JAW (eds) Contrast media: safety issues and ESUR guidelines, 2nd edn. Springer, Heidelberg, pp 187–196
Thomsen HS (2009) Nephrogenic systemic fibrosis: history and epidemiology. Radiol Clin N Am 47:827–831
Broome DR (2008) Nephrogenic systemic fibrosis associated with gadolinium based contrast agents: a summary of the medical literature reporting. Eur J Radiol 66:230–234
Idée J-M, Port M, Dencausse A, Lancelot E, Corot C (2009) Involvement of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: an update. Radiol Clin N Am 47:855–869
Evans CH (1990) The occurrence and metabolism of lanthanides. In: Biochemistry of the lanthanides. Plenum Press, New York, pp 285–337
Palasz A, Czekaj P (2000) Toxicological and cytophysiological aspects of lanthanides action. Acta Biochim Pol 47:1107–1114
Adding LC, Bannenberg GL, Gustafsson LE (2001) Basic experimental studies and clinical aspects of gadolinium salts and chelates. Cardiovasc Drug Rev 19:41–56
Korolenko TA, Dergunova MA, Alekseenko TV et al (2006) Intralysosomal accumulation of gadolinium and lysosomal damage during selective depression of liver macrophages in vivo. Bull Exp Biol Med 142:391–394
Spencer AJ, Wilson SA, Batchelor J et al (1997) Gadolinium chloride toxicity in the rat. Toxicol Pathol 25:245–255
De Haën C (2001) Conception of the first magnetic resonance imaging contrast agents; a brief history. Top Magn Reson Imaging 12:221–2230
Thomsen HS, Dawson P, Tweedle MF (2012) MR and CT contrast agents for perfusion imaging and regulatory issues. In: Bammer R (ed) MR & CT perfusion imaging: clinical applications and theoretical principles. Lippincott Williams & Wilkins, Philadelphia (in press)
Morcos SK (2009) Chelates and stability. In Thomsen HS, Webb JAW (eds) Contrast media: safety issues and ESUR guidelines, 2nd edn. Springer, Heidelberg, pp 155-160
Tweedle MF, Wedeking P, Kumar K (1995) Biodistribution of radiolabeled formulated gadopentetate, gadoteridol, gadoterate and gadodiamide in mice and rats. Invest Radiol 30:372–380
Pietsch H, Lengsfeld P, Jost G, Frenzel T, Hütter J, Sieber MA (2009) Long-term retention of gadolinium in the skin of rodents following the administration of gadolinium-based contrast agents. Eur Radiol 19:1417–1424
Evans CH, Drouven BJ (1983) The promotion of collagen polymerization by lanthanide and calcium ions. Biochem J 213:751–758
Brouven BJ, Evans CK (1986) Collagen fibrillogenesis in the presence of lanthanides. J Biol Chim 261:11792–11797
Brady T, Gore J (1991) Discussion. Presented at SMRM Workshop on Contrast Enhanced Magnetic Resonance, Napa, CA, May 23-25, 1991. Magn Reson Med 22:229–232
Müller N, Günzel P, Schöbel C (1992) Ionic and non-ionic gadolinium-containing magnetic resonance contrast media. Comparison of effects and their reversibility in repeated dose toxicity studies in rats. Adv MRI Contrast 1(Suppl 1):15–28
Edward M, Quinn JA, Mukherjee S et al (2008) Gadodiamide contrast agent ‘activates’ fibroblasts: a possible cause of nephrogenic systemic fibrosis. J Pathol 214:584–593
Morcos SK (2011) Experimental studies investigating the pathophysiology of nephrogenic systemic fibrosis; what did we learn so far? Eur Radiol 21:496–500
Abu-Alfa AK (2011) Nephrogenic systemic fibrosis and gadolinium-based contrast agents. Adv Chronic Kidney Dis 18:188–198
Thomsen HS (2010) Contrast-enhanced MRI in patients with impaired renal function: recent recommendations to minimize the risk of nephrogenic systemic fibrosis. Solutions Contrast Imaging 1:2–7
Marckmann P, Skov L (2009) Nephrogenic systemic fibrosis: clinical picture and treatment. Radiol Clin N Am 47:833–840
Marckmann P, Skov L, Rossen K et al (2008) Clinical manifestations of gadodiamide-related nephrogenic systemic fibrosis. Clin Nephrol 69:161–168
Giradi M, Kay J, Elston DM, LeBoit PE, Abu-Alfa A, Cowper SE (2011) Nephrogenic systemic fibrosis: clinicopathological definition and workup recommendations. J Am Acad Dermatol 65:1095–1106
Todd DJ, Kagan A, Chibnik LB, Kay J (2007) Cutaneous changes of nephrogenic systemic fibrosis. Predictor of early mortality and association with gadolinium exposure. Arthritis Rheum 56:3433–3441
Qureshi ZP, Bennett CL, Sator OA, Norris LB, Xirasagar A, Thomsen HS (2012) Gadolinium induced nephrogenic systemic fibrosis, the rise and fall of an iatrogenic disease. Clin Kidney J 5:82–88
Rydahl C, Thomsen HS, Marckman P (2008) High prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to gadodiamide, a Gadolinium(Gd)-containing magnetic resonance contrast agent. Invest Radiol 43:141–144
COMMISSION DECISION of 1.7.2010 concerning, in the framework of Article 31 of Directive 2001/83/EC of the European Parliament and of the Council, the marketing authorisations for Gadolinium-containing contrast agents for human use which contain one or more of the active substances “gadodiamide, gadopentetic acid, gadobenic acid, gadoxetic acid, gadoteridol, gadobutrol and gadoteric acid”. http://ec.europa.eu/health/documents/community-register/html/refh_others.htm. Accessed December 2011
Food and Drug Administration. Press Release September 9th 2010 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm225286.htm. Accessed October 1st 2010 Accessed December 2011
Wertman R, Altun E, Martin DR et al (2008) Risk of nephrogenic systemic fibrosis: evaluation of gadolinium chelate contrast agents at four American universities. Radiology 248:799–806
Elmholdt TR, Pedersen M, Jorgensen B et al (2011) Nephrogenic systemic fibrosis is found only among gadolinium-exposed patients with renal insufficiency: a case–control study from Denmark. Br J Dermatol 165:828–836
Tsushima Y, Kanal E, Thomsen HS (2010) Nephrogenic systemic fibrosis: risk factors suggested from Japanese published cases. Brit J Radiol 83:590–595
Marckmann P, Skov L, Rossen K, Heaf JG, Thomsen HS (2007) Case–control study of gadodiamide-related nephrogenic systemic fibrosis. Nephrol Dial Transplant 22:3174–3178
National Institute for Health and Clinical Excellence (2008) Early identification and management of Chronic kidney disease in adults in primaty and secondary care. www.nice.org.uk/CG073. Assessed June 17th 2012
Sena BF, Stern JP, Pandharipande PV et al (2010) Screening patients to assess renal function before administering gadolinium chelates: assessment of the Choyke questionnaire. AJR Am J Roentgenol 195:424–428
Maloo M, Abt P, Kashyap R et al (2006) Nephrogenic systemic fibrosis among liver transplant recipients: a single institution experience and topic update. Am J Transplant 6:2212–2217
Chow DS, Bahrami S, Raman SS et al (2011) Risk of nephrogenic systemic fibrosis in liver transplantation patients. AJR Am J Roentgenol 197:658–662
KDOQI Clinical Practice Guidelines for chronic kidney disease (2002) Evaluation, classification and stratification. Am J Kidney Dis 39:S1–S266
Grebe SO, Borrmann M, Altenburg A, Wesselman U, Hein D, Haage P (2008) Chronic inflammation and accelerated atherosclerosis as important cofactors in nephrogenic systemic fibrosis following intravenous gadolinium exposure. Clin Exp Nephrol 12:403–406
Heinz-Peer G, Neruda A, Watschinger B et al (2010) Prevalence of NSF following intravenous gadolinium-contrast media administration in dialysis patients with endstage renal disease. Eur J Radiol 76:12–34
Abraham JL, Thakral C, Skov L et al (2008) Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis. Brit J Dermatol 158:273–280
Sieber MA, Lengsfeld P, Frenzel T et al (2008) Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions. Eur Radiol 18:2164–2173
Wadas TJ, Sherman CD, Miner JH et al (2010) The biodistribution of [153Gd]Gd-labeled magnetic resonance contrast agents in a transgenic mouse model of renal failure differs greatly from control mice. Magn Reson Med 64:1274–1280
White GW, Gibby WA, Tweedle MF (2006) Comparison of Gd (DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy. Invest Radiol 41:272–278
Webb JAW (2009) Pregnancy and lactation. In: Thomsen HS, Webb JAW (eds) Contrast media: safety issues and ESUR Guidelines, 2nd edn. Springer, Heidelberg, pp 95–102
American College of Radiology. Manual of Contrast Media Version 7 2010 http://www.acr.org/SecondaryMainMenuCategories/quality_safety/contrast_manual/NephrogenicSystemicFibrosis.aspx. Accessed December 2011
Morcos SK, Thomsen HS, Webb JAW; Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) (2007) Dialysis and contrast media. Eur Radiol 12:3026–3030
Thomsen HS (2008) Is NSF only the tip of the “gadolinium toxicity” iceberg? J Magn Reson Imaging 28:284–286
Lind Ramskov K, Thomsen HS (2009) Nephrogenic systemic fibrosis and contrast medium-induced nephropathy: a choice between the devil and the deep blue sea for patients with reduced renal function? Acta Radiol 50:965–967
Martin DR, Semelka RC, Chapman A et al (2009) Nephrogenic systemic fibrosis versus contrast-induced nephropathy: risks and benefits of contrast-enhanced MR and CT renally impaired patients. J Magn Reson Imaging 30:1350–1356
Acknowledgements
Members of the Committee: H.S. Thomsen (Chairman, University of Copenhagen, Denmark), F. Stacul (Secretary, University of Trieste, Italy), T. Almén (University of Lund, Sweden), M.-F. Bellin (University of Paris, France), Michele Bertolotto (University of Trieste, Italy), G. Bongartz (University of Basle, Switzerland), O. Clement (University of Paris, France), G. Heinz-Peer (University of Vienna, Austria), Peter Leander (University of Lund, Sweden), S.K. Morcos (University of Sheffield, United Kingdom), P. Reimer (University of Freiburg, Germany), A. van der Molen (University of Leiden, the Netherlands), J.A.W. Webb (St. Bartholomew’s Hospital, United Kingdom). Consultants to the Committee: Eric Lancelot (Guerbet, France), P. Lengsfeld (Bayer Pharma, Germany), A. Spinazzi (Bracco, Italy). ESUR: www.esur.org
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Thomsen, H.S., Morcos, S.K., Almén, T. et al. Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines. Eur Radiol 23, 307–318 (2013). https://doi.org/10.1007/s00330-012-2597-9
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DOI: https://doi.org/10.1007/s00330-012-2597-9